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Gosvig K, Goller J, Hansson NH, Brandes A, Modrau I, Rasmussen LF, Eskesen K, Jensen AKG, Belley-Côté E, Whitlock R, Riber LPS. Rationale and design of the anticoagulant therapy after left atrial appendage closure (ATLAAC) trial. Am Heart J 2025; 287:86-93. [PMID: 40246048 DOI: 10.1016/j.ahj.2025.04.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 04/11/2025] [Accepted: 04/12/2025] [Indexed: 04/19/2025]
Abstract
INTRODUCTION Left atrial appendage closure (LAAC) has become a recommended addition to oral anticoagulation for patients with atrial fibrillation, who undergo cardiac surgery. The procedure significantly reduces the risk of stroke and systemic arterial embolism, potentially making oral anticoagulation (OAC) unnecessary or even harmful, when considering the associated increased risk of bleeding. This publication describes the rationale and design of a randomized trial, testing the hypothesis that stopping OAC is noninferior to continuing OAC after surgical LAAC in terms of the primary endpoint. METHODS The ATLAAC trial is a multicenter, randomized, controlled trial, aiming to enroll 1,220 patients with atrial fibrillation, who have undergone surgical LAAC and remain on OAC. A cardiac CT scan is performed to confirm success of the LAAC. Patients with successful closure are randomized to stop or continue OAC. The primary endpoint is the first occurrence of ischemic stroke, systemic arterial embolism, or major bleeding over an expected mean follow-up of 4 years. Secondary endpoints include all-cause mortality, cardiovascular mortality, any bleeding leading to hospitalization, blood transfusion, venous thromboembolism, myocardial infarction, and quality of life measures. TRIAL STATUS Enrollment for the ATLAAC trial began in March 2024. As of January 18th, 2025, 554 patients have been enrolled in the study and 319 patients have been randomized. Recruitment is expected to continue for approximately 12 months. Follow-up will be stopped once 128 primary endpoints have occurred. CONCLUSIONS The ATLAAC trial will evaluate the safety of stopping OAC after surgical LAAC. TRIAL REGISTRATION NUMBER EU-CT: 2022-502986-92-00, clinicaltrials.gov ID: NCT06401616.
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Affiliation(s)
- Kristina Gosvig
- Department of Cardiothoracic and Vascular Surgery, Odense University Hospital, Odense, Denmark; Department of Clinical Research, Research unit for Cardiac Surgery, University of Southern Denmark, Odense, Denmark.
| | - Julie Goller
- Department of Cardiothoracic and Vascular Surgery, Odense University Hospital, Odense, Denmark; Department of Clinical Research, Research unit for Cardiac Surgery, University of Southern Denmark, Odense, Denmark
| | | | - Axel Brandes
- Department of Cardiology, Esbjerg and Grindsted Hospital, Esbjerg, Denmark; Department of Regional Health Research, University of Southern Denmark, Esbjerg, Denmark
| | - Ivy Modrau
- Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, 8200 Aarhus N, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus C, Denmark
| | | | | | - Aksel Karl Georg Jensen
- Department of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark
| | - Emilie Belley-Côté
- Department of Surgery, McMaster University, Hamilton, Ontario, Canada; Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Richard Whitlock
- Department of Surgery, McMaster University, Hamilton, Ontario, Canada; Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Lars Peter Schødt Riber
- Department of Cardiothoracic and Vascular Surgery, Odense University Hospital, Odense, Denmark; Department of Clinical Research, Research unit for Cardiac Surgery, University of Southern Denmark, Odense, Denmark
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Ando T, Nazif T, Briasoulis A, Afonso L, Stebbins A, Marquis-Gravel G, Kosinski AS, Leon M, Vemulapalli S. Clinical outcomes of direct oral anticoagulant versus warfarin after transcatheter aortic valve replacement: From the STS/ACC TVT registry. Am Heart J 2025; 285:66-73. [PMID: 40020964 DOI: 10.1016/j.ahj.2025.02.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 02/16/2025] [Accepted: 02/19/2025] [Indexed: 03/03/2025]
Abstract
BACKGROUND Transcatheter aortic valve replacement (TAVR) recipients frequently have an indication for long-term oral anticoagulation, including atrial fibrillation or systemic thromboembolic disease. It remains unclear if there are differences in safety and effectiveness between direct oral anticoagulants (DOAC) and warfarin in this patient population. METHODS Clinical outcomes were compared between TAVR recipients receiving DOACs or warfarin using data from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) registry linked with Centers for Medicare & Medicaid Services claims data. The analysis included patients from the TVT registry who underwent successful TAVR and were discharged on either a DOAC or warfarin between January 2013 and May 2018. The primary outcome was any bleeding requiring hospitalization from discharge to 1 year. Secondary outcomes included all-cause mortality and stroke from discharge to 1 year. Multivariable Cox proportional hazards regression models were used to compare these outcomes between the 2 groups. RESULTS A total of 29,142 patients underwent TAVR and were discharged on oral anticoagulation, among whom 10,973 (37.7%) were discharged on a DOAC. The use of DOACs increased throughout the study period and exceed the use of warfarin by the final year (2018). The cumulative incidence of bleeding requiring hospitalization at 1 year (11.8% vs 15.2%, P < .001) and all-cause mortality (15.5% vs 17.5%, P < .001) was significantly lower in DOAC group while stroke (2.47% vs 2.39%, P = .64) was not statistically different between groups. In an adjusted model, the use of a DOAC as opposed to warfarin was associated with a significantly lower risk of bleeding requiring hospitalization (adjusted hazard ratio 0.49, 95% confidence interval 0.43-0.56), all-cause mortality (adjusted hazard ratio 0.61, 95% confidence interval 0.57-0.66), and stroke (adjusted hazard ratio 0.86, 95% confidence interval 0.81-0.92) (all P < .001). CONCLUSIONS In this analysis of TAVR recipients discharged on oral anticoagulation in a large U.S. registry, the use of a DOAC rather than warfarin was associated with a lower risk of bleeding requiring hospitalization, all-cause mortality, and stroke from discharge to 1 year. Future randomized studies will be necessary to establish the optimal choice of anticoagulant in TAVR patients.
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Affiliation(s)
- Tomo Ando
- Kawasaki Saiwai Hospital, Kawasaki, Kanagawa, Japan.
| | - Tamim Nazif
- New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY
| | | | - Luis Afonso
- Wayne State University, Detroit Medical Center, Detroit, MI
| | | | | | | | - Martin Leon
- Kawasaki Saiwai Hospital, Kawasaki, Kanagawa, Japan
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Guerrero-Hurtado M, García-Villalba M, Gonzalo A, Durán E, Martinez-Legazpi P, Ávila P, Kahn AM, Chen MY, McVeigh E, Bermejo J, Álamo JCD, Flores O. Hemodynamics affects factor XI/XII anticoagulation efficacy in patient-derived left atrial models. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2025; 267:108761. [PMID: 40318574 DOI: 10.1016/j.cmpb.2025.108761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 03/29/2025] [Accepted: 03/30/2025] [Indexed: 05/07/2025]
Abstract
BACKGROUND AND OBJECTIVE Atrial fibrillation (AF) is a common arrhythmia that disrupts blood circulation in the left atrium (LA), causing stasis in the left atrial appendage (LAA) and increasing thromboembolic risk. In patients at sufficiently high risk, anticoagulation is indicated. This benefit may be counterbalanced by an increased risk of bleeding. Novel anticoagulants under development, such as factor XI/XII inhibitors, may be associated with a lower bleeding risk. However, their efficacy in preventing thrombosis is not fully understood. We hypothesized that patient-specific flow patterns in the LA and LAA not only influence the risk of thrombosis but also the effectiveness of anticoagulation agents. METHODS To test our hypothesis, we simulated blood flow and the intrinsic coagulation pathway in patient-specific LA anatomies with and without factor XI/XII inhibition. We included a heterogeneous cohort of thirteen patients, some in sinus rhythm and others in AF, four of whom had an LAA thrombus or a history of transient ischemic attacks. We used computational fluid dynamics based on 4D CT imaging and a detailed 32-coagulation factor system to run 247 simulations. We analyzed baseline LA flow patterns and evaluated various factor XI/XII inhibition levels. Implementing a novel multi-fidelity coagulation modeling approach accelerated computations by two orders of magnitude, enabling many simulations to be performed. RESULTS The simulations provided spatiotemporally resolved maps of thrombin concentration throughout the LA, showing that it peaks inside the LAA. Coagulation metrics based on peak LAA thrombin dynamics suggested patients could be classified as having no, moderate or high thromboembolic risk. High-risk patients had slower flows and higher residence times in the LAA than those with moderate thromboembolic risk, and they required stronger factor XI/XII inhibition to prevent thrombin growth. These data suggest that the anticoagulation effect was also related to the LAA hemodynamics. CONCLUSION The methodology outlined in this study has the potential to enable personalized assessments of coagulation risk and to tailor anticoagulation therapy by analyzing flow dynamics in patient-derived LA models, representing a significant step towards advancing the application of digital twins in cardiovascular medicine.
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Affiliation(s)
- M Guerrero-Hurtado
- Department of Aerospace Engineering, Universidad Carlos III de Madrid, Leganés, Spain
| | - M García-Villalba
- Institute of Fluid Mechanics and Heat Transfer, TU Wien, 1060 Vienna, Austria
| | - A Gonzalo
- Department of Mechanical Engineering, University of Washington, Seattle, WA, USA
| | - E Durán
- Department of Mechanical, Thermal and Fluids Engineering, Universidad de Málaga, Málaga, Spain
| | - P Martinez-Legazpi
- Dept. of Mathematical Physics and Fluids, Universidad Nacional de Educación a Distancia, Spain; CIBERCV, Madrid, Spain
| | - P Ávila
- CIBERCV, Madrid, Spain; Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
| | - A M Kahn
- Division of Cardiovascular Medicine, University of California San Diego, La Jolla, CA, USA
| | - M Y Chen
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - E McVeigh
- Division of Cardiovascular Medicine, University of California San Diego, La Jolla, CA, USA; Department of Bioengineering, University of California San Diego, La Jolla, CA, USA; Department of Radiology, University of California San Diego, La Jolla, CA, USA
| | - J Bermejo
- CIBERCV, Madrid, Spain; Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
| | - J C Del Álamo
- Department of Mechanical Engineering, University of Washington, Seattle, WA, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA; Division of Cardiology, University of Washington, Seattle, WA, USA
| | - O Flores
- Department of Aerospace Engineering, Universidad Carlos III de Madrid, Leganés, Spain.
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Nishimura T, Aoki J, Sakamoto Y, Shiozawa M, Yoshimura S, Ihara M, Koga M, Anan Y, Fujimoto S, Terasawa Y, Sakai K, Iguchi Y, Terakado M, Suzuki F, Kimura K. Direct oral anticoagulants versus warfarin for the management of left atrial appendage thrombus in patients with acute stroke. J Neurol Sci 2025; 473:123516. [PMID: 40300361 DOI: 10.1016/j.jns.2025.123516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 04/11/2025] [Accepted: 04/21/2025] [Indexed: 05/01/2025]
Abstract
BACKGROUND We compared the effectiveness of direct oral anticoagulants (DOACs) and warfarin for resolving left atrial appendage (LAA) thrombus in patients with acute stroke with non-valvular atrial fibrillation (NVAF). METHODS Among consecutive patients with acute stroke admitted to five major comprehensive stroke centers in Japan between January 2017 and December 2022, those with NVAF and LAA thrombus detected by transesophageal echocardiography (TEE) and underwent follow-up TEE were included. All patients received DOAC or warfarin treatment. We compared the clinical characteristics, changes in LAA thrombus size, resolution, recurrent stroke, and bleeding complications within 3 months of stroke onset. RESULTS This study included 63 patients (DOAC group, 22; warfarin group, 41). Sex, age, and National Institutes of Health Stroke Scale scores on admission did not significantly differ between the groups. The initial LAA thrombus size was 0.83 cm2 and 0.88 cm2 in the DOAC and warfarin groups, respectively. On follow-up evaluation 10 days after initial TEE, LAA thrombus was completely resolved in 59 % and 34 % of patients in the DOAC and warfarin groups, respectively (P = 0.02). Multivariable analysis revealed DOAC treatment as an independent factor for LAA thrombus resolution (odds ratio, 3.21; 95 % confidence interval: 1.07-10.23, P = 0.04). Recurrent stroke occurred in one and three patients in the DOAC and warfarin groups, respectively. No intracerebral hemorrhage cases were observed in either group within 3 months of stroke onset. CONCLUSION In patients with acute stroke with NVAF and LAA thrombus detected by TEE, DOACs may be more effective than warfarin in resolving LAA thrombus.
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Affiliation(s)
- Takuya Nishimura
- Department of Neurology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Junya Aoki
- Department of Neurology, Tama-nagayama Hospital, Nippon Medical School, Tokyo, Japan
| | - Yuki Sakamoto
- Department of Neurology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Masayuki Shiozawa
- Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Sohei Yoshimura
- Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Masafumi Ihara
- Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Masatoshi Koga
- Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Yuhei Anan
- Division of Neurology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Shigeru Fujimoto
- Division of Neurology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Yuka Terasawa
- Department of Neurology, Brain Attack Center Ota Memorial Hospital, Hiroshima, Japan
| | - Kenichiro Sakai
- Department of Neurology, The Jikei University School of Medicine, Tokyo, Japan
| | - Yasuyuki Iguchi
- Department of Neurology, The Jikei University School of Medicine, Tokyo, Japan
| | - Mariko Terakado
- Department of Neurology, Tama-nagayama Hospital, Nippon Medical School, Tokyo, Japan
| | - Fumiaki Suzuki
- Department of Neurology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Kazumi Kimura
- Department of Neurology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
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Elshafei MN, Salem M, El-Bardissy A, Abdelmoneim MS, Khalil A, Elhadad S, Al Mistarihi M, Danjuma M. Comparative Effectiveness and Safety of Direct Oral Anticoagulants in Low Body Weight Patients with Atrial Fibrillation: A Systematic Review and Meta-analysis. Cardiovasc Drugs Ther 2025; 39:643-660. [PMID: 38165553 PMCID: PMC12116646 DOI: 10.1007/s10557-023-07537-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/29/2023] [Indexed: 01/04/2024]
Abstract
INTRODUCTION Direct oral anticoagulant (DOAC) agents are established as the anticoagulation strategy of choice for a variety of clinical risks. Despite this, uncertainty still exists with regard to their efficacy and safety for the prevention of stroke and systemic embolism in some patient populations; most notably those with low body weight (LBW) (<60 kg or body mass index [BMI] <18 kg/m2). Currently, there is a paucity of trial and non-trial data to support a prescriptive recommendation for their use in these patient cohorts. We have carried out a pooled systematic review of the most up to date published data of patients stabilized on various DOAC analogs with the view to ascertaining the exact matrices of their efficacy and safety in these cohorts of patients. METHODS We initially carried out a comprehensive search of databases from inception to June 2023 for eligible studies exploring the efficacy and safety of various analogs of direct oral anticoagulants in patients with atrial fibrillation who had low body weight. Databases accessed include PubMed, EMBASE, the Science Citation Index, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effectiveness. We carried out a weighted comparison of derived pooled odd ratios (with their corresponding confidence intervals) of mortality outcomes between various DOACs using the random effects model. RESULTS Thirteen studies (n = 165,205 patients) were included in our meta-analysis. DOAC analogs were associated with increased stroke-related events, composite outcome, and mortality in low body weight patients compared to non-low body weight patients (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.17-1.92), (OR 1.55, 95% CI 1.29-1.86), (OR 2.92, 95% CI 1.87-4.58), respectively. There was no significant difference in the safety outcome (major bleeding events) between the DOAC analogs (OR 1.19, 95% CI 0.93-1.52). DISCUSSION In this meta-analytical review comprising both real-world and randomized controlled studies, the use of DOAC analogs in low body weight patients (body weight of <60 kg or BMI<18 kg/m2) with atrial fibrillation was associated with increased risks of stroke-related events, composite outcomes, and mortality compared to non-low body weight cohorts patients. At the same time, there was no significant difference in terms of major bleeding events. This finding has provided the first resolution of pervading uncertainty surrounding the use of DOAC analogs in these patient cohorts and suggests the need for follow-up confirmatory systematic studies in this group of patients.
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Affiliation(s)
| | - Muhammad Salem
- Clinical Pharmacy Department, Hamad Medical Corporation, Doha, Qatar
| | - Ahmed El-Bardissy
- Clinical Pharmacy Department, Hamad Medical Corporation, Doha, Qatar
| | | | - Ahmed Khalil
- Clinical Pharmacy Department, Hamad Medical Corporation, Doha, Qatar
| | | | | | - Mohammed Danjuma
- Internal Medicine Department, Hamad Medical Corporation, Doha, Qatar
- Weill Cornell Medicine-Qatar, Doha, Qatar
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Kambara M, Ikawa F, Hidaka T, Yamamori Y, Yamamoto Y, Michihata N, Uchimura M, Yoshikane T, Akiyama Y, Horie N, Hayashi K. Lack of Association of Chronological Age and Antithrombotic Agents With Acute Intracranial Hemorrhage in the Group of Older Adults With Traumatic Brain Injury. Neurosurgery 2025; 96:1321-1332. [PMID: 39440941 DOI: 10.1227/neu.0000000000003240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Accepted: 09/06/2024] [Indexed: 10/25/2024] Open
Abstract
BACKGROUND AND OBJECTIVES Some reports suggest that older patients with traumatic brain injury (TBI) are more likely to experience acute intracranial hemorrhage, resulting in poor outcomes. However, the association between precise chronological age and use of antithrombotic agents with acute intracranial hemorrhage in these patients remains unknown. The aim of this study was to determine factors associated with acute intracranial hemorrhage and poor outcomes in patients with TBI, including chronological age and use of antithrombotic agents. METHODS Patients hospitalized for TBI between January 2006 and December 2021 were included. Patients were categorized by age groups of <65 years, 65 to 74 years, 75 to 84 years, and ≥85 years. Associations between each age group and acute intracranial hemorrhage, a poor outcome at discharge, and in-hospital mortality were evaluated. RESULTS The cohort included 1086 patients, with 713 (65.7%) in the ≥65 age group. Although chronological age was associated with acute intracranial hemorrhage in patients aged <65 years (odds ratio [OR] 1.02; 95% CI 1.01-1.03), it was not associated with patients aged ≥65 years. None of the antithrombotic agents investigated were associated with acute intracranial hemorrhage in the group aged ≥65 years. Although chronological age was associated with a poor outcome in patients aged <65 years (OR 1.03; 95% CI 1.01-1.07), it was not associated in those aged ≥65 years. The ≥85 year age group (OR 2.30; 95% CI 1.18-4.51) compared with <65 years were significantly associated with a poor outcome. None of the antithrombotic agents investigated were associated with a poor outcome in the group aged ≥65 years. CONCLUSION Our findings confirmed the lack of an association of chronological age and antithrombotic agents with acute intracranial hemorrhage in the group of older adults with TBI. Our findings suggest that antithrombotic agents may be safely used, even in older adults.
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Affiliation(s)
- Mizuki Kambara
- Department of Neurosurgery, Shimane University Faculty of Medicine, Izumo , Shimane , Japan
| | - Fusao Ikawa
- Department of Neurosurgery, Shimane University Faculty of Medicine, Izumo , Shimane , Japan
- Department of Neurosurgery, Shimane Prefectural Central Hospital, Izumo , Shimane , Japan
- Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima , Japan
| | - Toshikazu Hidaka
- Department of Neurosurgery, Shimane Prefectural Central Hospital, Izumo , Shimane , Japan
| | - Yuji Yamamori
- Department of Emergency and Critical Care Medicine, Shimane Prefectural Central Hospital, Izumo , Shimane , Japan
| | - Yoshiaki Yamamoto
- Department of Rehabilitation, Shimane Prefectural Central Hospital, Izumo , Shimane , Japan
| | - Nobuaki Michihata
- Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Bunkyo , Tokyo , Japan
| | - Masahiro Uchimura
- Department of Neurosurgery, Shimane University Faculty of Medicine, Izumo , Shimane , Japan
| | - Tsutomu Yoshikane
- Department of Neurosurgery, Shimane University Faculty of Medicine, Izumo , Shimane , Japan
| | - Yasuhiko Akiyama
- Department of Neurosurgery, Shimane University Faculty of Medicine, Izumo , Shimane , Japan
- Department of Neurosurgery, Sakurakai Hospital, Osakasayama , Osaka , Japan
| | - Nobutaka Horie
- Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima , Japan
| | - Kentaro Hayashi
- Department of Neurosurgery, Shimane University Faculty of Medicine, Izumo , Shimane , Japan
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Matusevicius M, Säflund M, Balestrino M, Cappellari M, Ferrandi D, Ghoreishi A, Peeters A, Rand V, De Michele M, Vilionskis A, Zini A, Ahmed N. Intravenous Thrombolysis in Patients Taking Direct Oral Anticoagulation Treatment Before Stroke Onset: Results from the Safe Implementations of Treatments in Stroke International Stroke Registry. Ann Neurol 2025; 97:1205-1214. [PMID: 39902556 PMCID: PMC12082013 DOI: 10.1002/ana.27189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 01/13/2025] [Accepted: 01/14/2025] [Indexed: 02/05/2025]
Abstract
OBJECTIVES Intravenous thrombolysis (IVT) is contraindicated for acute ischemic stroke (AIS) patients taking direct oral anticoagulants (DOACs) within 48 hours before index stroke. Limited data exist on off-label use of IVT for these patients. We compared the safety and outcomes of IVT in AIS patients with DOAC treatment and patients with no OAC before index stroke. METHODS We analyzed data from the Safe Implementations of Treatments in Stroke (SITS) International Stroke Thrombolysis Registry during 2013-2024. Outcomes were symptomatic intracerebral hemorrhage (SICH) by the SITS Monitoring Study and European Cooperative Acute Stroke Study II definitions, functional independency (modified Rankin Scale score 0-2), and death by 3 months. Propensity score matching with a nearest neighbor matching algorithm with a ratio of 1:2 was used for relevant clinical variables. We also analyzed the time from last DOAC dose to IVT treatment. RESULTS A total of 1,311 DOAC and 129,384 no OAC patients were included. We matched 894 patients with DOAC to 1,788 with no OAC. The mean age was 75 years versus 76 years, and the median National Institutes of Health Stroke Scale score 11 versus 12, respectively. Patients with DOAC had a similar proportion of outcomes compared with patients with no OAC: SICH per SITS Monitoring Study (1.1 vs 1.5%, p = 0.50), SICH per European Cooperative Acute Stroke Study II (4.0 vs 4.3%, p = 0.82), any parenchymal hematoma (6.3 vs 7.8, p = 0.22), and functional independency (47.9 vs 46.4%, p = 0.59) and death (25.1 vs 24.0%, p = 0.65) at 3-month follow-up. The time from last DOAC dose to IVT did not affect outcomes. INTERPRETATION In this observational study, we did not find any difference in outcomes after IVT therapy in AIS patients with DOAC compared with no OAC treatment before index stroke. ANN NEUROL 2025;97:1205-1214.
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Affiliation(s)
- Marius Matusevicius
- Department of NeurologyKarolinska University HospitalStockholmSweden
- Department of Clinical NeuroscienceKarolinska InstituteStockholmSweden
| | - Malin Säflund
- Department of NeurologyKarolinska University HospitalStockholmSweden
- Department of Clinical NeuroscienceKarolinska InstituteStockholmSweden
| | - Maurizio Balestrino
- Department of Neuroscience (DINOGMI)University of GenoaGenoaItaly
- IRCCS Policlinico San MartinoGenoaItaly
| | - Manuel Cappellari
- Stroke Unit‐Azienda Ospedaliera Universitaria Integrata VeronaVeronaItaly
| | - Delfina Ferrandi
- SC Neurologia Azienda Ospedaliera Universitaria Santi Antonio e BiagioAlessandriaItaly
| | - Abdoreza Ghoreishi
- Stroke Research Group, Vali‐e‐Asr Hospital, Department of Neurology and Stroke Unit, School of MedicineZanjan University of Medical SciencesZanjanIran
| | - André Peeters
- Department of NeurologyCliniques Universitaires St LucBrusselsBelgium
| | - Viiu‐Marika Rand
- Department of NeurologyNorth Estonia Medical CenterTallinnEstonia
| | - Manuela De Michele
- Hospital Policlinico Umberto I, Emergency Department, Stroke UnitSapienza UniversityRomeItaly
| | | | - Andrea Zini
- IRCCS Istituto Delle Scienze Neurologiche di BolognaBolognaItaly
| | - Niaz Ahmed
- Department of NeurologyKarolinska University HospitalStockholmSweden
- Department of Clinical NeuroscienceKarolinska InstituteStockholmSweden
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8
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Zhao X, Luo J, Pan X, Fang L, Liu C. Efficacy and safety of anticoagulants in elderly atrial fibrillation patients: a systematic review and network meta-analysis. BMC Cardiovasc Disord 2025; 25:396. [PMID: 40413387 DOI: 10.1186/s12872-025-04867-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2025] [Accepted: 05/15/2025] [Indexed: 05/27/2025] Open
Abstract
BACKGROUND Atrial fibrillation (AF) disproportionately affects elderly populations, raising concerns about balancing efficacy and safety in anticoagulation therapy. OBJECTIVE To assess the efficacy and safety of various anticoagulants in elderly AF patients through a systematic review and network meta-analysis. METHODS We systematically searched PubMed, MEDLINE, Embase, and Web of Science for randomized controlled trials (RCTs) up to September 10, 2024, involving AF patients aged 75 years and older. Outcomes included stroke, major and non-major bleeding, all-cause mortality, and cardiovascular mortality. Statistical analysis was performed using a Bayesian random-effects network meta-analysis model to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Surface under the cumulative ranking curve (SUCRA) was used to rank treatments. RESULTS Fourteen RCTs involving 16,261 participants were included, with 13 RCTs analyzing stroke (14675 patients), 14 RCTs major bleeding (16261 patients), 6 RCTs non-major bleeding (1074 patients), 7 RCTs all-cause mortality (10128 patients), and 4 RCTs cardiovascular mortality (7704 patients). Edoxaban 15 mg once daily significantly reduced stroke incidence compared to warfarin (OR = 0.30, 95% CI: 0.12-0.71) and placebo (OR = 0.29, 95% CI: 0.20-0.42), ranking highest in stroke prevention (SUCRA = 90.6%). Dabigatran 110 mg twice daily reduced the risk of major bleeding (OR = 0.18, 95% CI: 0.04-0.76) compared to rivaroxaban 15 mg. Rivaroxaban 10 mg (OR = 0.35, 95% CI: 0.13-0.94) and edoxaban 15 mg (OR = 0.67, 95% CI: 0.46-0.99) demonstrated significant reductions in adverse events compared to placebo. No significant differences were observed across treatments for all-cause or cardiovascular mortality. CONCLUSION Edoxaban 15 mg and Rivaroxaban 10 mg provide an optimal balance between efficacy and safety in elderly AF patients. These findings support the need for personalized anticoagulant selection to maximize therapeutic benefit in this high-risk population.
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Affiliation(s)
- Xingran Zhao
- Department of Hospital-acquired infection control, The People's Hospital of Leshan, Leshan, 246000, China
| | - Jun Luo
- Ministry of Basic Medical Education, Dazhou Vocational College of Chinese Medicine, Dazhou, 635000, Sichuan, China
| | - Xuanda Pan
- Department of General Practice, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong Province, China
| | - Linlin Fang
- Department of Critical Care Medicine, Affiliated Anqing First People's Hospital of Anhui Medical University, Anqing, 246000, China.
| | - Chengjiang Liu
- Department of General Medicine, Affiliated Anqing First People's Hospital of Anhui Medical University, Anqing, 246000, China.
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9
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Mitchell A, Watson MC, Welsh TJ, McGrogan A. Safety and effectiveness of anticoagulation therapy in older people with atrial fibrillation during exposed and unexposed treatment periods. Heart 2025; 111:565-574. [PMID: 39961639 DOI: 10.1136/heartjnl-2024-324763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 01/12/2025] [Indexed: 05/25/2025] Open
Abstract
BACKGROUND Anticoagulation therapy reduces stroke risk in patients with atrial fibrillation (AF), but it is often underused in older populations due to concerns about bleeding. This study aimed to compare the safety and effectiveness of anticoagulation during periods of exposure and non-exposure and across different anticoagulants in people with AF aged ≥75 years. METHODS Using UK primary care data from the Clinical Practice Research Datalink (2013-2017), a retrospective cohort study was conducted on patients newly prescribed oral anticoagulants (warfarin or direct oral anticoagulants). Exposure to anticoagulation was mapped using prescription data. Cox regression models were used to estimate adjusted HRs for stroke, bleeding, myocardial infarction, and death during periods of exposure and non-exposure and for different anticoagulants. RESULTS Among 20 167 patients (median age 81 years), non-exposure to anticoagulation was associated with higher risks of stroke (HR 3.07, 95% CI 2.39 to 3.93), myocardial infarction (HR 1.85, 95% CI 1.34 to 2.56) and death (HR 2.87, 95% CI 2.63 to 3.12) compared with exposure. Compared with warfarin, apixaban was associated with lower risks of non-major bleeding (HR 0.73, 95% CI 0.64 to 0.85), whereas rivaroxaban was associated with higher risks of major (HR 1.33, 95% CI 1.15 to 1.55) and non-major (HR 1.29, 95% CI 1.16 to 1.44) bleeding. CONCLUSIONS Non-exposure to anticoagulation increases the risks of stroke, myocardial infarction and death in older patients with AF. Clinicians should carefully weigh the risks of discontinuing anticoagulation and provide shared decision-making support to patients, especially when considering deprescription.
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Affiliation(s)
- Anneka Mitchell
- Department of Life Sciences, University of Bath, Bath, UK
- Pharmacy Department, Plymouth Hospitals NHS Foundation Trust, Plymouth, UK
| | - Margaret C Watson
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, Glasgow, UK
| | - Tomas J Welsh
- The ReMind UK Centre, Royal United Hospital Bath NHS Trust, Bath, Bath and North East Somerset, UK
- Institute of Clinical Neurosciences, University of Bristol, Bristol, UK
| | - Anita McGrogan
- Department of Life Sciences, University of Bath, Bath, UK
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10
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Nakajima E, Ha ACT, Qiu F, Austin PC, Jackevicius CA, Ko DT, Dorian P, Lee DS, Abdel-Qadir H. East Asian immigration and direct oral anticoagulant dosing for atrial fibrillation: A population-based cohort study. Heart Rhythm 2025:S1547-5271(25)02500-7. [PMID: 40412595 DOI: 10.1016/j.hrthm.2025.05.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 05/09/2025] [Accepted: 05/14/2025] [Indexed: 05/27/2025]
Abstract
BACKGROUND Some East Asian (EA) guidelines recommend lower doses of direct oral anticoagulants (DOACs) for atrial fibrillation (AF) than in North America and Europe. OBJECTIVE Investigate the association of immigration from EA with DOAC dosing and outcomes in AF. METHODS Population-based cohort study using administrative databases of Ontario immigrants with AF aged ≥66 years who were dispensed DOAC prescriptions from 2012-2019. Birth country was classified as EA or not. We used multivariable logistic regression to assess the association of EA birth with DOAC dose and cause-specific hazards regression for the association of EA birth and DOAC dose with stroke/bleeding/death. Interaction between EA birth and DOAC dosing was studied for each outcome. RESULTS Among 14,421 immigrants, 3958 (27.4%) were born in EA. EA immigrants had lower odds of receiving full-dose DOACs versus non-EA immigrants (OR 0.64, 95%CI 0.58-0.69, p<0.001). EA birth was not associated with a composite of hospitalization for stroke/bleeding (HR 0.97, 95%CI 0.84-1.12, p= 0.67) nor hospitalization for stroke (HR 0.86, 95%CI 0.71-1.04, p= 0.13), but was associated with higher bleeding hazard (HR 1.15, 95%CI 1.02-1.30, p= 0.02) and lower mortality (HR 0.91, 95%CI 0.84-0.99, p= 0.04). There was no significant interaction between EA birth and DOAC dosing for stroke (p=0.41), bleeding (p=0.27), or death (p=0.33). CONCLUSIONS EA immigrants were less likely to receive full-dose DOACs and had a higher bleeding hazard, similar stroke hazard, and lower mortality risk than non-EA immigrants. There was no evidence that DOAC dosing had a differential treatment effect in EA immigrants.
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Affiliation(s)
- Erika Nakajima
- Women's College Hospital, Toronto, ON, Canada; Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Andrew C T Ha
- Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada
| | - Feng Qiu
- ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, ON, Canada
| | - Peter C Austin
- ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, ON, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada
| | - Cynthia A Jackevicius
- ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, ON, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada; Western University of Health Sciences, Pomona, California
| | - Dennis T Ko
- ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, ON, Canada; Schulich Heart Centre, Sunnybrook Health Sciences Center, Toronto, ON, Canada
| | - Paul Dorian
- Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada
| | - Douglas S Lee
- Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada; ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, ON, Canada
| | - Husam Abdel-Qadir
- Women's College Hospital, Toronto, ON, Canada; Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada; ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, ON, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada.
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11
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McCabe JJ, Cheung Y, Foley M, Brennan SO, Buckley J, Renom PC, Cassidy T, Collins R, Dolan E, Grosse GM, Harbison J, James K, Khadjooi K, Induruwa I, Katan M, Maher S, O’Connor M, O’Donnell M, Purroy F, Synott P, Kelly PJ. Residual Risk of Recurrent Stroke Despite Anticoagulation in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis. JAMA Neurol 2025:2834593. [PMID: 40394992 PMCID: PMC12096328 DOI: 10.1001/jamaneurol.2025.1337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Accepted: 02/14/2025] [Indexed: 05/22/2025]
Abstract
Importance Atrial fibrillation (AF) is a leading cause of stroke, and oral anticoagulants (OAC) reduce this risk. However, there are limited data on the residual risk of recurrent stroke in patients with AF. Objective To determine the recurrent stroke risk in patients with AF by performing a systematic review and meta-analysis. Data Sources Eligible studies were identified by searching Ovid MEDLINE and Embase from inception (Ovid: January 1946; Embase: January 1970) until January 2025. Study Selection Eligible studies enrolled patients with prior ischemic stroke and AF, reported information on incidence of recurrent stroke, and had follow-up data for 1 or more years. Three reviewers independently screened abstracts and performed full-text reviews. Data Extraction and Synthesis Data extraction was performed by 2 reviewers and independently verified by a third. Incidence rates were pooled using random-effects meta-analysis. Analysis was repeated in patients whose qualifying event occurred despite OAC. Study quality was assessed using the Quality In Prognosis Studies tool. Main Outcomes and Measures The primary outcome was recurrent ischemic stroke. The secondary outcomes were any recurrent stroke (ischemic stroke or intra-cerebral hemorrhage [ICH]) and ICH during follow-up. Results A total of 23 studies were identified, which included 78 733 patients and 140 307 years of follow-up. The median proportion of OAC use across studies was 92%. The pooled incidence of recurrent ischemic stroke was 3.75% per year (95% CI, 3.17%-4.33%). The risk was higher in noninterventional observational cohorts (4.20% per year; 95% CI, 3.41%-4.99%) compared with randomized clinical trials (2.26% per year; 95% CI, 1.96%-2.57%) (P value for interaction <.001). The risk of any recurrent stroke was 4.88% per year (95% CI, 3.87%-5.90%), and the risk of ICH was 0.58% per year (95% CI, 0.43%-0.73%). In patients with stroke despite OAC, the risk was 7.20% per year (95% CI, 5.05%-9.34%) for ischemic stroke, 8.96% per year (95% CI, 8.25%-9.67%) for any stroke, and 1.40% per year (95% CI, 0.40%-2.40%) for ICH. Conclusions and Relevance In this systematic review and meta-analysis, even with modern prevention therapy, the residual recurrence risk after AF-related stroke is high, with an estimated 1 in 6 patients experiencing a recurrent ischemic stroke at 5 years. These data demonstrate an urgent need to improve our understanding of the biological processes responsible for recurrence, improve risk stratification, and develop new secondary prevention strategies after AF-related stroke.
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Affiliation(s)
- John J. McCabe
- Health Research Board Stroke Clinical Trials Network Ireland, Dublin, Ireland
- School of Medicine, University College Dublin, Dublin, Ireland
- Stroke Service, Department of Geriatric Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Yuen Cheung
- Health Research Board Stroke Clinical Trials Network Ireland, Dublin, Ireland
- School of Medicine, University College Dublin, Dublin, Ireland
- Stroke Service, Department of Geriatric Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Marianne Foley
- Health Research Board Stroke Clinical Trials Network Ireland, Dublin, Ireland
- School of Medicine, University College Dublin, Dublin, Ireland
- Stroke Service, Department of Geriatric Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Stephen O. Brennan
- Health Research Board Stroke Clinical Trials Network Ireland, Dublin, Ireland
- School of Medicine, University College Dublin, Dublin, Ireland
- Stroke Service, Department of Geriatric Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Jane Buckley
- Health Research Board Stroke Clinical Trials Network Ireland, Dublin, Ireland
- School of Medicine, University College Dublin, Dublin, Ireland
- Stroke Service, Department of Geriatric Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Pol Camps Renom
- Department of Neurology, Institute of Biomedical Research Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Tim Cassidy
- Health Research Board Stroke Clinical Trials Network Ireland, Dublin, Ireland
- Stroke Service, Department of Geriatric Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
- Department of Geriatric Medicine, St Vincent’s University Hospital, Dublin, Ireland
| | - Ronan Collins
- Health Research Board Stroke Clinical Trials Network Ireland, Dublin, Ireland
- Department of Geriatric Medicine, Tallaght University Hospital, Dublin, Ireland
| | - Eamon Dolan
- Health Research Board Stroke Clinical Trials Network Ireland, Dublin, Ireland
- Department of Geriatric Medicine, James Connolly Hospital, Dublin, Ireland
| | - Gerrit M. Grosse
- Department of Neurology and Stroke Center, University Hospital Basel, Basel, Switzerland
| | - Joseph Harbison
- Health Research Board Stroke Clinical Trials Network Ireland, Dublin, Ireland
- Department of Geriatric Medicine, St James’s Hospital, Dublin, Ireland
| | - Kirstyn James
- Health Research Board Stroke Clinical Trials Network Ireland, Dublin, Ireland
- Department of Geriatric Medicine, Cork University Hospital, Cork, Ireland
| | - Kayvan Khadjooi
- Department of Clinical Neurosciences, Addenbrooke’s Hospital, University of Cambridge, Cambridge, United Kingdom
| | - Isuru Induruwa
- Department of Clinical Neurosciences, Addenbrooke’s Hospital, University of Cambridge, Cambridge, United Kingdom
| | - Mira Katan
- Department of Neurology and Stroke Center, University Hospital Basel, Basel, Switzerland
| | - Senan Maher
- Health Research Board Stroke Clinical Trials Network Ireland, Dublin, Ireland
| | - Margaret O’Connor
- Health Research Board Stroke Clinical Trials Network Ireland, Dublin, Ireland
- Department of Geriatric Medicine, Limerick University Hospital, Limerick, Ireland
| | - Martin O’Donnell
- Health Research Board Stroke Clinical Trials Network Ireland, Dublin, Ireland
- College of Medicine, Nursing and Health Sciences, University of Galway and University Hospital Galway, Galway, Ireland
| | - Francisco Purroy
- Stroke Unit, Department of Neurology, Hospital Universitari Arnau de Vilanova de Lleida, Lleida, Spain
| | - Padraig Synott
- Health Research Board Stroke Clinical Trials Network Ireland, Dublin, Ireland
- School of Medicine, University College Dublin, Dublin, Ireland
- Stroke Service, Department of Geriatric Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Peter J. Kelly
- Health Research Board Stroke Clinical Trials Network Ireland, Dublin, Ireland
- School of Medicine, University College Dublin, Dublin, Ireland
- Stroke Service, Department of Neurology, Mater Misericordiae University Hospital, Dublin, Ireland
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12
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Subash R, Strakosch T, Zhang M, Hagan M, Dworatzek E, Kisser A, Vasilopoulos V, Salter C, Dickerson C, Stawowczyk E. Cost-effectiveness and budget impact analysis of switching from apixaban to rivaroxaban treatment among patients with nonvalvular atrial fibrillation in a German healthcare setting. J Comp Eff Res 2025:e250008. [PMID: 40396210 DOI: 10.57264/cer-2025-0008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/22/2025] Open
Abstract
Aim: Direct oral anticoagulant (DOAC) switching often occurs in patients with nonvalvular atrial fibrillation (NVAF) for medical and nonmedical reasons. Limited data describe the economic consequences of DOAC switching in patients with NVAF. This study evaluates the cost-effectiveness and budget impact of initiating apixaban and switching to rivaroxaban versus initiating and continuing apixaban for patients with NVAF, from a German payer perspective. Materials & methods: Built on an existing model, a cohort-level lifetime Markov model was developed, including dynamic pricing assumptions to account for anticipated generic entry of DOACs. The modeled population (n = 1000) included German patients with NVAF, eligible for oral anticoagulation, who initiated on apixaban. The primary model outcome was the incremental cost-effectiveness ratio, assessed using cost per quality-adjusted life year (QALY) gained and a willingness-to-pay threshold of €48,750/QALY. A secondary model outcome was a 5-year budget impact analysis. Results: Switching patients from apixaban to rivaroxaban led to 285 additional events per 1000 patient years, resulting in 0.079 fewer QALYs and higher total costs per patient (€21,357 vs €16,390 for apixaban continuers). In the base case analysis (with generic pricing assumptions), switching from apixaban to rivaroxaban was dominated (i.e., less effective and more costly) by continuing apixaban. In the budget impact analysis (with generic pricing assumptions), switching from apixaban to rivaroxaban led to additional cumulative costs of €490 per patient over 5 years. Conclusion: Despite the introduction of generic discounting, switching patients with NVAF from apixaban to rivaroxaban led to higher total costs and fewer QALYs under base case assumptions, meaning apixaban switchers were dominated by apixaban continuers from a German payer perspective. Switching patients from apixaban to rivaroxaban also led to greater budget impact over 5 years.
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Affiliation(s)
| | | | - Michelle Zhang
- Bristol Myers Squibb Company, NJ, US
- University of Southern California, LA, US
| | | | | | | | | | - Chloe Salter
- Health Economics & Outcomes Research Ltd, Cardiff, UK
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13
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Dangas GD, Unverdorben M, Nicolas J, Hengstenberg C, Chen C, Möllmann H, Jin J, Shawl F, Yamamoto M, Saito S, Hambrecht R, Duggal A, Van Mieghem NM. Comparing Major Gastrointestinal Bleeding in Patients Receiving Edoxaban Versus Warfarin After Transcatheter Aortic Valve Replacement: Results From the Randomized ENVISAGE-TAVI AF Trial. J Am Heart Assoc 2025; 14:e033321. [PMID: 40371611 DOI: 10.1161/jaha.123.033321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 12/13/2024] [Indexed: 05/16/2025]
Abstract
BACKGROUND Non-vitamin K oral anticoagulants are recommended over vitamin K antagonists in patients with nonvalvular atrial fibrillation (AF). However, the risk of gastrointestinal bleeding may be higher with non-vitamin K oral anticoagulants versus vitamin K antagonists. Patients after successful transcatheter aortic valve replacement (TAVR) who are elderly and frail have worse outcomes with major gastrointestinal bleeding (MGIB), including death. This study evaluated incidence, predictors, and impact of MGIB among patients with AF after successful TAVR. METHODS This on-treatment analysis of ENVISAGE-TAVI AF (Edoxaban Compared to Standard Care After Heart Valve Replacement Using a Catheter in Patients With Atrial Fibrillation) included patients who received ≥1 dose of the study drug. Demographic, clinical, and procedural characteristics were compared between patients with versus without an MGIB event. Cox multivariable regression analysis identified predictors of MGIB. RESULTS Of 1377 patients in this analysis, 83 (6.0%) experienced MGIB, with 56 (67.5%) of these patients receiving edoxaban. Patients with versus without MGIB were more likely to have undergone percutaneous coronary intervention ≤30 days before TAVR (9.6% versus 4.2%; P=0.03), a higher ejection fraction (mean±SD, 58.0±10.4 versus 55.3±11.5; P=0.04), and carotid artery disease (13.3% versus 6.6%; P=0.04). Edoxaban without dose adjustment versus vitamin K antagonist use (P=0.003), smoking (P=0.01), low hemoglobin levels (P<0.0001), and percutaneous coronary intervention ≤30 days before TAVR (P=0.01) emerged as predictors of MGIB. CONCLUSIONS In this ENVISAGE-TAVI AF subanalysis, MGIB occurred in 6.0% of patients with prevalent or incident AF undergoing TAVR, and those receiving edoxaban versus vitamin K antagonists had a higher risk of MGIB. A priori identification of risk factors for MGIB may help optimize outcomes for patients with AF undergoing TAVR. REGISTRATION URL: https://www.clinicaltrials.gov; unique identifier: NCT02943785.
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Affiliation(s)
- George D Dangas
- Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Hospital New York NY USA
- School of Medicine National and Kapodistrian University of Athens Athens Greece
| | | | - Johny Nicolas
- Icahn School of Medicine at Mount Sinai The Mount Sinai Hospital New York NY USA
| | - Christian Hengstenberg
- Department of Internal Medicine II, Division of Cardiology Vienna General Hospital, Medical University Vienna Austria
| | - Cathy Chen
- Daiichi Sankyo, Inc. Basking Ridge NJ USA
| | - Helge Möllmann
- Department of Internal Medicine St. Johannes-Hospital Dortmund Germany
| | - James Jin
- Daiichi Sankyo, Inc. Basking Ridge NJ USA
| | - Fayaz Shawl
- Interventional Cardiology, Adventist HealthCare White Oak Medical Center Silver Spring MD USA
| | | | - Shigeru Saito
- Division of Cardiology & Catheterization Laboratories Shonan Kamakura General Hospital Kamakura Japan
| | - Rainer Hambrecht
- Bremer Institute for Heart and Circulation Research at Klinikum Links der Weser Bremen Germany
| | | | - Nicolas M Van Mieghem
- Department of Cardiology Erasmus University Medical Centre, Thoraxcenter Rotterdam The Netherlands
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14
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Thapa S, Mandal B, Shah S, Mehta R, Sah S, Thapa A, Chand S, Medicherla C, Kitago T, Frishman WH, Aronow WS. Stroke Prevention in Atrial Fibrillation: A systematic Review and Meta-Analysis of Left Atrial Appendage Occlusion Versus Direct Oral Anticoagulants. Cardiol Rev 2025:00045415-990000000-00503. [PMID: 40392596 DOI: 10.1097/crd.0000000000000954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/22/2025]
Abstract
Atrial fibrillation significantly increases the risk of ischemic stroke, with thrombi primarily originating in the left atrial appendage (LAA). While direct oral anticoagulants (DOACs) are the standard for stroke prevention, LAA occlusion (LAAO) has emerged as a nonpharmacologic alternative, particularly for patients at high bleeding risk. A systematic review and meta-analysis included 15 studies (1 randomized control trial and 14 observational studies) encompassing 22,420 patients (10,704 LAAO, 11,716 DOAC). LAAO and DOACs demonstrated comparable thromboembolic event rates. LAAO was associated with significantly lower risks of stroke/transient ischemic attack (risk ratio: 0.86, P = 0.0004), major bleeding [hazard ratio (HR): 0.74, P = 0.03], cardiovascular mortality (HR: 0.57, P < 0.00001), and all-cause mortality (risk ratio 0.66, P = 0.006). The composite outcome significantly favored LAAO (HR: 0.67, P = 0.0008). No significant difference was found in intracranial bleeding rates.
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Affiliation(s)
- Sangharsha Thapa
- From the Department of Neurology, Westchester Medical Center, New York Medical College, Valhalla, NY
| | - Bishal Mandal
- Department of Public Health, Institute of Medicine, Tribhuvan University, Maharajgunj, Kathmandu, Nepal
| | - Sangam Shah
- Department of Public Health, Institute of Medicine, Tribhuvan University, Maharajgunj, Kathmandu, Nepal
| | - Rachana Mehta
- Department of Medicine, National Public Health Laboratory, Teku, Kathmandu, Nepal
| | - Sanjit Sah
- Department of Medicine, Korea University, Seoul, South Korea
- Department of Public Health Dentistry, D.Y. Patil Dental College and Hospital, Maharashtra, India
| | - Anish Thapa
- Department of Medicine, Universal College of Medical Sciences, Bhairahawa, Nepal
| | - Swati Chand
- Departments of Cardiology and Medicine, Westchester Medical Center, New York Medical College, Valhalla, NY
| | - Chaitanya Medicherla
- From the Department of Neurology, Westchester Medical Center, New York Medical College, Valhalla, NY
| | - Tomoko Kitago
- From the Department of Neurology, Westchester Medical Center, New York Medical College, Valhalla, NY
| | | | - Wilbert S Aronow
- Departments of Cardiology and Medicine, Westchester Medical Center, New York Medical College, Valhalla, NY
- Department of Medicine, New York Medical College, Valhalla, NY
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15
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Galli M, Angiolillo DJ. Direct oral anticoagulants in stroke prevention of atrial fibrillation patients: can we rely on them in all clinical scenarios? Future Cardiol 2025:1-3. [PMID: 40372808 DOI: 10.1080/14796678.2025.2506915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Accepted: 05/13/2025] [Indexed: 05/17/2025] Open
Affiliation(s)
- Mattia Galli
- Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
| | - Dominick J Angiolillo
- Division of Cardiology, University of Florida College of Medicine, Jacksonville, FL, USA
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16
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Ryan D, Feng W, Liu AJ. Cerebrovascular Management Considerations in Patients on AATs. J Clin Med 2025; 14:3420. [PMID: 40429415 PMCID: PMC12112173 DOI: 10.3390/jcm14103420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2025] [Revised: 05/06/2025] [Accepted: 05/12/2025] [Indexed: 05/29/2025] Open
Abstract
The prevalence of Alzheimer's Disease (AD) is increasing worldwide, with more emergency providers and neurologists expecting to encounter these patients. The paradigm of management of AD is expected to change given the recent approval of anti-amyloid therapies (AATs). The most concerning complication of these therapies is amyloid-related imaging abnormalities (ARIA), which can lead to an increased risk of cerebrovascular complications. Given a growing population of patients with AD and growing use of AATs, providers must be prepared to manage patients at risk of cerebrovascular disease and those presenting with neurologic deficits. This subpopulation warrants a unique approach given the risk of ischemic stroke and the associated risk of hemorrhage present in the use of AATs. In this narrative review, we present and propose management considerations in the acute stroke setting and patients at risk of cerebrovascular disease, including patients with indications for anticoagulation, to most appropriately manage this special population. Future cross-disciplinary collaboration and use of registry data will be essential to narrow management approaches and develop safety data.
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Affiliation(s)
- Dylan Ryan
- Department of Neurology, Duke University School of Medicine, Durham, NC 27704, USA
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17
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Oto E, Okutucu S, Öztürk DK, Ata N, Yavuz B, Gale C, Camm AJ, Pieper KS, Kakkar AK, Oto A. A new score with superior stroke risk prediction in atrial fibrillation: entropy-based information gain approaches in a large nationwide cohort. J Interv Card Electrophysiol 2025:10.1007/s10840-025-02053-4. [PMID: 40369260 DOI: 10.1007/s10840-025-02053-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Accepted: 04/21/2025] [Indexed: 05/16/2025]
Abstract
BACKGROUND Risk scores have been used to assess stroke risk in atrial fibrillation (AF) for reducing ischemic stroke and bleeding risk. Information gain ratio (IGR) is an entropy-based parameter that shows which clinical score is more informative for prediction of the clinical endpoint. OBJECTIVE Herein, we aimed to generate and validate a stroke risk score based on the TuRkish Atrial Fibrillation (TRAF) data. METHODS We used a split-sample approach to develop and internally validate the new stroke risk score. Based on multivariate logistic regression analysis, we generated CHADS-F in the anticoagulation naïve TRAF cohort (274,631 patients). CHADS-F stands for Cardiac failure (1 point), hypertension (1 point), age (≥ 65-69 = 1 point, ≥ 70-74 = 2 points ≥ 75 = 3 points), diabetes (1 point), stroke (2 points), and older female (1 point) (≥ 65). External validation was performed in the "Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF)" Registry. Informative capacity and accuracy of the CHADS-F score was compared with CHADS2 and CHA2DS2-VASc scores. RESULTS In anticoagulation naïve cohort, CHADS-F (IGR for all cohort: 0.7526) outperforms both the CHADS2 (IGR for all cohort: 0.6340) and CHA2DS2-VASc (IGR for all cohort: 0.6969) in terms of the IGR for ischemic stroke and systemic embolism. Receiver operating characteristic curves revealed highest accuracy for the CHADS-F score [area under curve for CHADS-F: 0.743, CHADS2: 0.722, and CHA2DS2-VASc: 0.722]. CHADS-F had good discriminative abilities at predicting clinical endpoints in the GARFIELD-AF registry. CONCLUSION The CHADS-F score had higher informative capacity and accuracy than the current CHADS2 and CHA2DS2-VASc scores for predicting stroke and systemic embolism.
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Affiliation(s)
- Emre Oto
- UHS Wilson Medical Center, Johnson City, NY, USA
| | | | | | - Naim Ata
- Social Security Institution, Ankara, Turkey
| | | | - Chris Gale
- Leeds Institute of Cardiovascular, and Metabolic Medicine, Leeds, UK
| | - A John Camm
- St. George's University of London, London, UK
| | - Karen S Pieper
- Department of Clinical Research, Thrombosis Research Institute (TRI), London, UK
| | - Ajay K Kakkar
- Department of Clinical Research, Thrombosis Research Institute (TRI), London, UK
- Department of Surgery, University College London, London, UK
| | - Ali Oto
- Department of Cardiology, Memorial Ankara Hospital, P.O: 06520, Cankaya/Ankara, Turkey.
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Duy Mai T, Ho THQ, Hoang SV, Nguyen HTT, Pandian J, Nguyen TV, Vu KT, Tran GS, Dao VP, Tran MC, Pham HM. Comparative Analysis of the Net Clinical Benefit of Direct Oral Anticoagulants in Atrial Fibrillation: Systematic Review and Network Meta-analysis of Randomised Controlled Trials. Eur Cardiol 2025; 20:e13. [PMID: 40395561 PMCID: PMC12090073 DOI: 10.15420/ecr.2025.07] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2025] [Accepted: 03/09/2025] [Indexed: 05/22/2025] Open
Abstract
Background Direct oral anticoagulants (DOACs) are the standard treatment for stroke prevention in AF. However, high-quality head-to-head comparisons of DOACs are lacking. This study compared oral anticoagulants in patients with AF. Methods Data were retrieved from eligible randomised controlled trials (RCTs). Interventions were ranked using the surface under the cumulative ranking curve (SUCRA) and the frequentist random effects model was applied. Efficacy outcomes included stroke, systemic embolism, MI, and all-cause mortality; the safety outcome was major bleeding. A composite outcome of efficacy and net clinical benefit was also evaluated. Results From 23,152 records, 11 eligible RCTs were identified and included in the study. Rivaroxaban was superior to vitamin K antagonists (VKA) in net clinical benefit (RR 0.75; 95% CI [0.59-0.94]; p=0.0133), but there were no significant differences between other DOACs and VKA or among the DOACs themselves. Rivaroxaban reduced the risk of the composite outcome of efficacy compared with dabigatran (RR 0.85; 95% CI [0.75-0.98]; p=0.02) and edoxaban (RR 0.84; 95% CI [0.75-0.95]; p=0.0051), but not apixaban (RR 0.89; 95% CI [0.89-1.02]; p=0.087). All DOACs showed superiority over VKA in efficacy, without an increased risk of major bleeding. Based on the SUCRA, rivaroxaban showed a favourable risk-benefit profile compared with the other anticoagulants. Conclusion This study showed that DOACs are superior to VKA in efficacy without increasing major bleeding risk, with rivaroxaban demonstrating the most balanced risk-benefit profile. Well-designed RCTs are needed to validate these findings.
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Affiliation(s)
- Ton Duy Mai
- Stroke Centre, Bach Mai HospitalHanoi, Vietnam
- Faculty of Stroke and Cerebrovascular Disease, VNU University of Medicine and PharmacyHanoi, Vietnam
- Department of Emergency and Critical Care Medicine, Hanoi Medical UniversityHanoi, Vietnam
| | | | - Sy Van Hoang
- Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh City, Vietnam
- Cardiovascular Department, Cho Ray HospitalHo Chi Minh City, Vietnam
| | - Hoai Thi Thu Nguyen
- Department of Internal Medicine, VNU University of Medicine and PharmacyHanoi, Vietnam
- Vietnam National Heart Institute, Bach Mai HospitalHanoi, Vietnam
| | - Jeyaraj Pandian
- Department of Neurology, Christian Medical CollegeLudhiana, India
| | - Tan Van Nguyen
- Department of Geriatrics and Gerontology, University of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh City, Vietnam
- Department of Interventional Cardiology, Thong Nhat HospitalHo Chi Minh City, Vietnam
| | - Khoa Tien Vu
- Medical Affairs Department, Bayer VietnamHo Chi Minh City, Vietnam
| | - Giang Song Tran
- Vietnam National Heart Institute, Bach Mai HospitalHanoi, Vietnam
| | - Viet Phuong Dao
- Stroke Centre, Bach Mai HospitalHanoi, Vietnam
- Faculty of Stroke and Cerebrovascular Disease, VNU University of Medicine and PharmacyHanoi, Vietnam
- Department of Emergency and Critical Care Medicine, Hanoi Medical UniversityHanoi, Vietnam
| | - Minh Cong Tran
- Nuffield Department of Clinical Neuroscience, University of OxfordOxford, UK
| | - Hung Manh Pham
- Department of Cardiology, Ha Noi Medical UniversityHanoi, Vietnam
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Atreja N, Dubey A, Kohli M, Jiang J, Hagan M, Aweh G, Adams S, Cheng D. Demographic and Socio-Economic Disparities in the Outcomes Among Patients with NVAF Treated with Oral Anticoagulants: A Real-World Evaluation of Medicare Beneficiaries. J Clin Med 2025; 14:3252. [PMID: 40364283 PMCID: PMC12072770 DOI: 10.3390/jcm14093252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2025] [Revised: 04/23/2025] [Accepted: 04/29/2025] [Indexed: 05/15/2025] Open
Abstract
Objectives: To assess the association between apixaban use and the risk of stroke/systemic embolism (SE) and major bleeding (MB) compared with other anticoagulants (OACs) across demographic and socio-economic subgroups in the treatment of nonvalvular atrial fibrillation (NVAF). Methods: The study included adult NVAF patients initiating OAC treatment between 2013 and 2019 in the Medicare database. Inverse probability treatment weighted Cox proportional hazard models were used to assess stroke/SE and MB outcomes across various subgroups. Results: Overall, the adjusted risks of stroke/SE and MB were lower for apixaban compared with warfarin (stroke/SE: HR, 0.69, [95% confidence interval (CI): 0.65-0.74], MB: 0.59 [95% CI: 0.57-0.60]), rivaroxaban (stroke/SE: 0.88 [95% CI: 0.84-0.92], MB: 0.60 [95% CI: 0.58-0.61]) and dabigatran (stroke/SE: 0.88 [95% CI: 0.80-0.95], MB: 0.76 [95% CI: 0.72-0.80]). Among the low socio-economic status (SES) group, apixaban was associated with lower risk vs. warfarin (stroke/SE: 0.73 [95% CI: 0.69-0.77], MB: 0.60 [95% CI: 0.57-0.62]) and rivaroxaban (stroke/SE: 0.88 [95% CI: 0.83-0.94], MB: 0.61 [95% CI: 0.59-0.63]). Among medium SES patients, apixaban was associated with lower risk vs. warfarin (stroke/SE: 0.67 [95% CI: 0.63-0.71] MB: 0.60 [95% CI: 0.58-0.63]), rivaroxaban (stroke/SE: 0.85 [95% CI: 0.79-0.91], MB: 0.59 [95% CI: 0.56-0.61]) and dabigatran (stroke/SE: 0.85 [95% CI: 0.73-0.99], MB: 0.77 [95% CI: 0.70-0.84]). Apixaban was also associated with lower risks of stroke/SE and MB compared with other OACs among most other demographic, socio-economic subgroups. Conclusions: Apixaban was associated with lower risk of stroke/SE and MB than warfarin, rivaroxaban, dabigatran across most demographic, socio-economic subgroups.
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Affiliation(s)
- Nipun Atreja
- Bristol Myers Squibb, Lawrenceville, NJ 08648, USA
| | | | | | - Jenny Jiang
- Bristol Myers Squibb, Lawrenceville, NJ 08648, USA
| | | | | | | | - Dong Cheng
- Bristol Myers Squibb, Lawrenceville, NJ 08648, USA
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20
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Lagrave J, Domingo L, Barceló-Vidal J, Comas M, Jimenez C, Ferrández O, Castells X, Sala M. Association between oral anticoagulant therapy and in-hospital complications and mortality. Br J Clin Pharmacol 2025. [PMID: 40331313 DOI: 10.1002/bcp.70087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 03/05/2025] [Accepted: 04/15/2025] [Indexed: 05/08/2025] Open
Abstract
AIMS This study aimed to identify patterns of direct oral anticoagulant (DOAC) and vitamin K antagonist (VKA) use in hospitalized patients and to examine their association with in-hospital haemorrhagic complications and mortality. METHODS An observational cross-sectional study was conducted among hospitalized patients ≥18 years from 2018 to 2022. Data on hospital discharges were obtained from the minimum data set and were matched with pharmacy records to identify patients treated with DOACs or VKAs. In-hospital haemorrhagic complications and mortality rates were calculated for study groups. Multivariate logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs), adjusting for age, sex and comorbidities. Analyses were stratified by medical and surgical profiles. Statistical significance was set at .05. RESULTS The study included 74 190 patients, with 4774 receiving DOACs and 1768 VKAs. During the study period, DOAC use increased by 45.11%. DOAC-treated patients had lower complication rates than those treated with VKAs (1.9 vs. 2.8%, respectively; P = .032). DOAC use was linked to a lower risk of haemorrhagic complications in surgical patients (OR = 0.65; 95%CI: 0.35-0.91), while in medical patients, the reduction in risk was not statistically significant (OR = 0.59; 95%CI: 0.33-1.10). No effect on mortality risk was observed among medical and surgical patients. CONCLUSIONS The increased use of DOACs among hospitalized patients showed a protective effect against haemorrhagic complications in surgical patients, supporting their increasing use in hospital settings.
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Affiliation(s)
- Juliana Lagrave
- Hospital del Mar Research Institute, Barcelona, Spain
- Department of Epidemiology and Evaluation, Hospital del Mar, Barcelona, Spain
| | - Laia Domingo
- Hospital del Mar Research Institute, Barcelona, Spain
- Department of Epidemiology and Evaluation, Hospital del Mar, Barcelona, Spain
- RICAPPS. Research Network on Chronicity, Primary Care, and Prevention and Health Promotion, Carlos III Health Institute, Madrid, Spain
| | - Jaime Barceló-Vidal
- Medicines Area and Pharmacy Service, Barcelona Territorial Management, Institut Català de la Salut, Barcelona, Spain
| | - Mercè Comas
- Hospital del Mar Research Institute, Barcelona, Spain
- Department of Epidemiology and Evaluation, Hospital del Mar, Barcelona, Spain
- RICAPPS. Research Network on Chronicity, Primary Care, and Prevention and Health Promotion, Carlos III Health Institute, Madrid, Spain
| | - Carmen Jimenez
- Hospital del Mar Research Institute, Barcelona, Spain
- Department of Hematology, Hospital del Mar, Barcelona, Spain
| | - Olivia Ferrández
- Hospital del Mar Research Institute, Barcelona, Spain
- Department of Pharmacy, Hospital del Mar, Barcelona, Spain
| | - Xavier Castells
- Hospital del Mar Research Institute, Barcelona, Spain
- Department of Epidemiology and Evaluation, Hospital del Mar, Barcelona, Spain
- RICAPPS. Research Network on Chronicity, Primary Care, and Prevention and Health Promotion, Carlos III Health Institute, Madrid, Spain
| | - Maria Sala
- Hospital del Mar Research Institute, Barcelona, Spain
- Department of Epidemiology and Evaluation, Hospital del Mar, Barcelona, Spain
- RICAPPS. Research Network on Chronicity, Primary Care, and Prevention and Health Promotion, Carlos III Health Institute, Madrid, Spain
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21
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Wong CK, Wong YK, Chan YH, Lin M, Hai JSH, Yiu KH, Lip GY, Lau KK, Tse HF. Concomitant Drug Interactions With Non-Vitamin K Oral Anticoagulants Are Associated With Bleeding and Mortality Risk in Patients With Nonvalvular Atrial Fibrillation. J Am Heart Assoc 2025; 14:e038668. [PMID: 40243197 DOI: 10.1161/jaha.124.038668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 02/26/2025] [Indexed: 04/18/2025]
Abstract
BACKGROUND Non-vitamin K oral anticoagulants prevent stroke and systemic embolism in patients with nonvalvular atrial fibrillation. However, potential drug interactions with concomitant medications may compromise their efficacy and escalate the risk of adverse effects. METHODS AND RESULTS We conducted a territory-wide retrospective cohort study in Hong Kong, focusing on nonvalvular atrial fibrillation prescribed non-vitamin K oral anticoagulants. The objective was to investigate the associated risk of gastrointestinal bleeding, intracranial hemorrhage, hospitalization for major bleeding, and all-cause mortality in relation to various concomitant medications. Our analysis included 22 568 patients with nonvalvular atrial fibrillation (aged 75.7 ± 10.8 years; 51.2% men) taking non-vitamin K oral anticoagulants from January 1, 2017, to December 31, 2020, totaling 40 317 patient-years. It was found that amiodarone (hazard ratio [HR], 1.53), digoxin (HR, 1.30), diltiazem (HR, 1.18), clarithromycin (HR, 4.98), and fluconazole (HR, 2.38) were associated with increased gastrointestinal bleeding, whereas amiodarone (HR, 2.20) and digoxin (HR, 1.61) were associated with increased intracranial hemorrhage. Furthermore, amiodarone (HR, 1.64), digoxin (HR, 1.35), clarithromycin (HR, 4.18), and fluconazole (HR, 2.40) were associated with increased hospitalization for major bleeding. Additionally, amiodarone (HR, 2.65), digoxin (HR, 1.85), diltiazem (HR, 1.44), verapamil (HR, 1.80), antidepressants (HR, 1.31), and fluconazole (HR, 3.27) were associated with increased all-cause mortality. Conversely, dronedarone (HR, 0.56) and atorvastatin (HR, 0.86) were associated with a significant reduction in all-cause mortality. CONCLUSIONS For patients with nonvalvular atrial fibrillation taking non-vitamin K oral anticoagulants, several concurrent medications were associated with increased risks of intracranial hemorrhage, major bleeding hospitalizations, and overall mortality.
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Affiliation(s)
- Chun-Ka Wong
- Department of Medicine, School of Clinical Medicine Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong SAR China
| | - Yuen-Kwun Wong
- Department of Medicine, School of Clinical Medicine Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong SAR China
| | - Yap-Hang Chan
- Department of Medicine, School of Clinical Medicine Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong SAR China
| | - Minqing Lin
- Department of Medicine, School of Clinical Medicine Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong SAR China
| | - Jojo Siu-Han Hai
- Department of Medicine, School of Clinical Medicine Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong SAR China
| | - Kai-Hang Yiu
- Department of Medicine, School of Clinical Medicine Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong SAR China
- Cardiac and Vascular Center The University of Hong Kong-Shenzhen Hospital Shenzhen China
| | - Gregory Yh Lip
- Liverpool Centre for Cardiovascular Science University of Liverpool and Liverpool Heart and Chest Hospital Liverpool UK
- Department of Clinical Medicine Aalborg University Aalborg Denmark
| | - Kui-Kai Lau
- Department of Medicine, School of Clinical Medicine Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong SAR China
| | - Hung-Fat Tse
- Department of Medicine, School of Clinical Medicine Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong SAR China
- Cardiac and Vascular Center The University of Hong Kong-Shenzhen Hospital Shenzhen China
- Hong Kong-Guangdong Stem Cell and Regenerative Medicine Research Centre The University of Hong Kong and Guangzhou Institutes of Biomedicine and Health Hong Kong SAR China
- Centre for Translational Stem Cell Biology Hong Kong SAR China
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22
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Mohan A, Chen H, Deshmukh AA, Wanat M, Essien EJ, Paranjpe R, Fatima B, Abughosh S. Marginal structural models to evaluate the association between adherence to direct oral anticoagulants and safety or efficacy outcomes among patients with atrial fibrillation. J Am Pharm Assoc (2003) 2025; 65:102355. [PMID: 39956296 DOI: 10.1016/j.japh.2025.102355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 11/27/2024] [Accepted: 02/11/2025] [Indexed: 02/18/2025]
Abstract
BACKGROUND Although the management of atrial fibrillation (AF) has improved over the years, suboptimal adherence to direct oral anticoagulants (DOACs) is a major health concern. Adherence and long-term persistence to DOACs decline over time resulting in increased risks of stroke, major bleeding, and death. OBJECTIVE This study aimed to evaluate the association between adherence to DOACs and composite or bleeding events using marginal structural models (MSMs). METHODS A retrospective study was conducted using the Medicare Advantage Plan from January 2016 to December 2020. Patients with AF prescribed any DOACs were identified. Adherence was calculated using the proportion of days covered (PDC). Patients with PDC ≥ 0.80 were considered adherent. Composite (stroke, systemic embolism, acute coronary syndrome) and bleeding (major and minor) events were calculated for each of the 4 time periods. An MSM was conducted to estimate the association between adherence and composite efficacy or bleeding events by controlling for time-dependent covariates and time-dependent exposure affected by the previous exposure. RESULTS A total of 1969 patients with AF were included in the study. Adherence was suboptimal during all the 5 time periods, and it ranged from 39.8% to 53.12%. This study did not find any significant association between adherence to DOACs and composite efficacy or bleeding events. The safety and efficacy outcomes were comparable among apixaban, rivaroxaban, and dabigatran. CONCLUSION This study revealed that adherence declined over time among old patients with AF. Future studies should explore the association between adherence to DOACs and health outcomes for a longer duration of follow-up using MSM.
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23
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Winstén AK, Langén V, Airaksinen KEJ, Teppo K. Net Benefit of Anticoagulation in Subclinical Device-Detected Atrial Fibrillation. JAMA Netw Open 2025; 8:e258461. [PMID: 40314955 PMCID: PMC12048845 DOI: 10.1001/jamanetworkopen.2025.8461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 03/02/2025] [Indexed: 05/03/2025] Open
Abstract
Importance The role of anticoagulation for stroke prevention in patients with device-detected atrial high-rate episodes, also known as subclinical atrial fibrillation (AF), is a subject of equipoise. Objective To assess the net benefit of nonvitamin K antagonist oral anticoagulants (NOACs) in patients with device-detected subclinical AF. Design, Setting, and Participants Decision analytical model run with 10 000 patients with anticoagulation and 10 000 patients without anticoagulation in a clinical scenario of deciding whether to start NOACs for stroke prevention in patients with subclinical AF. A Markov decision model was conducted on October 1, 2024, to estimate net outcomes of NOACs. The patients had stroke risk and bleeding risks similar to those of patients in randomized trials of anticoagulation in subclinical AF. Exposure Anticoagulation was modeled to decrease the risk of ischemic stroke by 32% and increase the risk of major bleeding by 62%. In probabilistic sensitivity analyses, the 95% CIs for treatment effect sizes were also considered. Main Outcomes and Measures The main outcome measure for overall net benefit was the cumulative quality-adjusted life-years (QALYs) during the simulation. The model considered the number and severity of ischemic strokes, hemorrhagic strokes, other intracranial bleeds, and extracranial bleeds, as well as the number of deaths during a 10-year simulation. Results When comparing the 2 cohorts of 10 000 patients (mean age, 77 years; 3700 [37%] women), those receiving NOAC therapy had 233 fewer ischemic strokes (21.7%), 55 fewer deaths (1.1%), and 453 more major bleeding events (37.3%) over a 10-year simulation period. Per patient, these differences translated to approximately 1 additional quality-adjusted week of life (0.024 QALYs) with NOAC treatment during the 10-year simulation. When the 95% CIs of treatment effect sizes were considered in probabilistic sensitivity analysis, there was a 65.8% probability that NOAC treatment leads to more QALYs than withholding treatment. Conclusions and Relevance In this analytical model study, initiating NOACs in patients with device-detected subclinical AF was associated with a minimal increase in QALYs. However, the benefits were uncertain, and the effect size of the overall net benefit does not appear to be clinically meaningful.
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Affiliation(s)
- Aleksi K. Winstén
- Department of Mathematics and Statistics, University of Turku, Turku, Finland
- Faculty of Medicine, University of Turku, Turku, Finland
| | - Ville Langén
- Division of Medicine, Turku University Hospital and University of Turku, Turku, Finland
| | | | - Konsta Teppo
- Heart Centre, Turku University Hospital, Turku, Finland
- Department of Life Technologies, University of Turku, Turku, Finland
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24
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Ibrahim A, Shalabi L, Zreigh S, Ramadan S, Mourad S, Eljadid G, Beshr M, Abdelaziz A, Elhadi M, Sabouret P, Mamas M. Comparative Efficacy and Safety of Low-Dose Direct Oral Anticoagulants Versus Dual Antiplatelet Therapy Following Left Atrial Appendage Occlusion in Patients With Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis. Catheter Cardiovasc Interv 2025; 105:1311-1319. [PMID: 39980323 DOI: 10.1002/ccd.31461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Revised: 02/04/2025] [Accepted: 02/09/2025] [Indexed: 02/22/2025]
Abstract
BACKGROUND Left atrial appendage occlusion (LAAO) is an alternative to chronic oral anticoagulation (OAT) for stroke prevention in nonvalvular atrial fibrillation (NVAF) patients with contraindications to OAT. Postprocedure antithrombotic therapy (ATT) is essential to reduce the risk of device-related thrombosis (DRT), but the optimal regimen remains uncertain. AIMS This study aims to compare the safety and efficacy of low-dose direct oral anticoagulants (DOACs) versus dual antiplatelet therapy (DAPT) following LAAO. METHODS A comprehensive search of PubMed, Scopus, Cochrane, and Web of Science was conducted in August 2024. Studies comparing low-dose DOACs and DAPT post-LAAO were included. The primary outcomes were a composite efficacy endpoint (DRT, strokes, and systemic embolism [SE]) and major bleeding events as the safety endpoint. Secondary outcomes included all bleeding events, all-cause mortality, and a composite of efficacy and safety endpoints. RESULTS Four studies with 727 patients were included. Low-dose DOACs were associated with lower rates of the primary composite efficacy endpoint compared to DAPT (OR = 0.36; 95% CI [0.16, 0.85], p = 0.01). No significant difference in major bleeding events was observed (OR = 0.36; 95% CI [0.11, 1.18]; p = 0.091; I² = 0%). Compared to DAPT, low-dose DOACs were also associated with lower rates of DRT events (OR = 0.36; 95% CI [0.16, 0.79], p = 0.011). CONCLUSION Low-dose DOACs effectively reduce thromboembolic events post-LAAO without increasing bleeding risk. These findings support their use as a viable ATT option, but larger trials are needed to confirm optimal regimens.
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Affiliation(s)
- Ahmed Ibrahim
- Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Laila Shalabi
- Faculty of Medicine, Gharyan University, Gharyan, Libya
| | - Sofian Zreigh
- Faculty of Medicine, Ankara Yıldırım Beyazıt University, Ankara, Turkey
| | | | - Sohaila Mourad
- Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | | | - Mohammed Beshr
- Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, Yemen
| | - Ali Abdelaziz
- Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Muhammed Elhadi
- Korea University College of Medicine, Seongbuk-gu, Seoul, Republic of Korea
| | - Pierre Sabouret
- National College of French Cardiologists, Paris, France
- ACTION Study Group, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
| | - Mamas Mamas
- Keele Cardiovascular Research Group, Keele University, Stoke-on-Trent, UK
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25
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Bulhões E, Antunes VLJ, Alexandre C, Defante MLR, Mazetto R, Oliveira VMR, Sousa PA, Guida C, Scanavacca MI, Darrieux F. Efficacy and safety of DOACs vs vitamin K antagonists in patients with atrial fibrillation and chronic kidney disease undergoing hemodialysis: A systematic review and meta-analysis of randomized controlled trials with trial sequential analysis. Heart Rhythm 2025; 22:1210-1217. [PMID: 39923948 DOI: 10.1016/j.hrthm.2025.02.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Revised: 01/15/2025] [Accepted: 02/01/2025] [Indexed: 02/11/2025]
Abstract
BACKGROUND Atrial fibrillation (AF) is a relatively prevalent arrhythmia in patients with kidney failure requiring dialysis who face a high risk of stroke and bleeding and for whom anticoagulation is a challenging decision. Although direct oral anticoagulants (DOACs) may offer advantages over vitamin K antagonists (VKAs), their use in this patient profile remains unclear. OBJECTIVE We conducted a systematic review and meta-analysis to compare DOACs and VKAs in patients with AF undergoing dialysis. METHODS PubMed, Embase, and Cochrane Central databases were analyzed. The outcomes analyzed were total stroke (a composite of ischemic and hemorrhagic stroke), ischemic stroke, all-cause death, cardiovascular death, myocardial infarction, major bleeding, clinically relevant nonmajor bleeding and gastrointestinal bleeding. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random effects model. R software version 4.3.2 R Studio for Statistical Computing, Vienna, Austria) was used for statistical analyses. Heterogeneity was assessed with I2 statistics. RESULTS The final analysis included 486 patients from 4 randomized controlled trial studies. The median follow-up ranged from 5.8 to 18 months. Although a reduction in total stroke was observed in the group receiving DOACs (RR 0.40; 95% CI 0.17-0.92; P = .031; I2 = 0%), no significant difference was found between the groups for ischemic stroke (RR 0.42; 95% CI 0.17-1.04; P = .062; I2 = 0%). In addition, a statistically significant reduction in major bleeding was noted in the DOAC group (RR 0.64; 95% CI 0.41-0.98; P = .044; I2 = 0%). However, no significant differences were observed among the groups for all-cause death (RR 0.88; 95% CI 0.57-1.35; P = .567; I2 = 47%), cardiovascular death (RR 1.13; 95% CI 0.60-2.10; P = .700; I2 = 0%), or clinically relevant nonmajor bleeding (RR 1.11; 95% CI 0.67-1.84; P = .669; I2 = 0%). CONCLUSION In this meta-analysis, DOACs were associated with a lower risk of total stroke and major bleeding. However, DOACs and VKA groups exhibited similar rates of ischemic stroke, all-cause and cardiovascular death, clinically relevant nonmajor bleeding, and gastrointestinal bleeding.
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Affiliation(s)
- Elísio Bulhões
- Faculty of Higher Superior of the Amazon Reunida, Medicine Department, Pará, Brazil.
| | - Vanio L J Antunes
- Federal University of Health Sciences of Porto Alegre, Medicine Department, Porto Alegre, Brazil
| | | | | | - Roberto Mazetto
- Amazonas State University, Medicine Department, Manaus, Brazil
| | | | | | - Camila Guida
- Dante Pazzanese Institute of Cardiology, Division of Cardiology, São Paulo, Brazil
| | | | - Francisco Darrieux
- Instituto do Coração (InCor), University of São Paulo, Arrhythmia Unit, São Paulo, Brazil
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Sukkha S, Chumnumwat S, Thongsoi P, Sonsiri R, Lohachatinante A, Kittikunkanyakit N, Chawanasuntharapot R, Kongwatcharapong J. Evaluation of DOAC Dosing Among Various Renal Equations in Patients With Kidney Impairment and Elderly in Thailand. Clin Transl Sci 2025; 18:e70238. [PMID: 40285384 PMCID: PMC12032188 DOI: 10.1111/cts.70238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 03/08/2025] [Accepted: 04/15/2025] [Indexed: 04/29/2025] Open
Abstract
The Thai Food and Drug Administration (TFDA) has approved direct oral anticoagulant (DOAC) dosing based on estimated creatinine clearance, eCrCl (Cockcroft-Gault equation). However, other renal function equations are often used in practice for patients with kidney disease, leading to potential discrepancies in DOAC dosing recommendations. The actual DOAC dosing patterns in resource-limited countries remain underreported. This cross-sectional study included patients with renal impairment who were treated at the outpatient department of Siriraj Hospital, Mahidol University, Thailand. Patients received their first DOAC for atrial fibrillation from January 2019 to December 2022. The primary objective was to evaluate the percentage of DOAC prescriptions compliant with TFDA guidelines using eCrCl. We also examined dosing agreement when substituting estimated glomerular filtration rate, eGFR (CKD-EPI) for eCrCl. Patient factors and the incidence of stroke and bleeding over a one-year follow-up were also assessed. A total of 326 patients and 1587 DOAC prescriptions were analyzed. The mean patient age was 79.1 ± 9.2 years, with a mean eGFR of 45.6 ± 9.9 mL/min/1.73 m2. TFDA-compliant dosing was observed in 68.2% of prescriptions. Dose disagreement between eGFR and eCrCl was 45%, with a trend toward overdosing using eGFR. An eGFR of less than 45 mL/min/1.73 m2 was associated with dose discrepancies. Stroke and bleeding incidences were low, with no differences across DOAC types. While most Thai patients received appropriate DOAC dosing, one-third did not comply with TFDA guidelines. Using eGFR instead of eCrCl may result in dosing differences, particularly in moderate to severe renal impairment.
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Affiliation(s)
- Sayamon Sukkha
- Clinical Pharmacy Division, Department of Pharmacy, Faculty of PharmacyMahidol UniversityBangkokThailand
| | - Supatat Chumnumwat
- Clinical Pharmacy Division, Department of Pharmacy, Faculty of PharmacyMahidol UniversityBangkokThailand
| | - Pattaranun Thongsoi
- Clinical Pharmacy Division, Department of Pharmacy, Faculty of PharmacyMahidol UniversityBangkokThailand
| | - Rawiphon Sonsiri
- Clinical Pharmacy Division, Department of Pharmacy, Faculty of PharmacyMahidol UniversityBangkokThailand
| | - Apisara Lohachatinante
- Clinical Pharmacy Division, Department of Pharmacy, Faculty of PharmacyMahidol UniversityBangkokThailand
| | - Nuttanun Kittikunkanyakit
- Clinical Pharmacy Division, Department of Pharmacy, Faculty of PharmacyMahidol UniversityBangkokThailand
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Luojus A, Lehto M, Halminen O, Lehtonen O, Niemi M, Teppo K, Kuoppala J, Haukka J, Putaala J, Linna M, Mustonen P, Aro A, Hartikainen J, Lip GYH, Airaksinen KEJ. Reduced dose direct oral anticoagulants and time-in-therapeutic-range defined warfarin in new-onset atrial fibrillation: a report from the nationwide FinACAF study. EUROPEAN HEART JOURNAL OPEN 2025; 5:oeaf046. [PMID: 40357260 PMCID: PMC12066950 DOI: 10.1093/ehjopen/oeaf046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Revised: 03/07/2025] [Accepted: 04/15/2025] [Indexed: 05/15/2025]
Abstract
Aims Direct oral anticoagulants (DOACs) at reduced dosage regimens are the first choice of ischaemic stroke (IS) prevention for patients with atrial fibrillation (AF) and elevated bleeding risk or renal insufficiency. We compared the outcomes of reduced dose DOACs and warfarin. Methods and results We included all new-onset patients with AF in Finland from 2011 to 2018. Adjusted hazard ratios (HRs) for IS, intracranial haemorrhage (ICH), bleeding, and mortality were calculated for dabigatran (n = 2 672), rivaroxaban (n = 1 866), apixaban (n = 3 936), and warfarin (n = 43 548). Patients on warfarin were grouped into quartiles by their individual time-in-therapeutic range (TTR), with the second best TTR quartile as a reference group for comparisons. Risk of IS was highest in the low TTR quartiles of warfarin, lowest in the best TTR quartile (0.65 95% confidence interval, 0.51-0.83), and did not differ for dabigatran, rivaroxaban, and apixaban compared with the second best TTR quartile. Risk of ICH was highest in low TTR quartiles of warfarin (HRs 7.20, 5.48-9.46 and 1.91, 1.44-2.55), and was not different in patients on dabigatran, rivaroxaban, and apixaban. Risk of all-cause death and bleeding were lowest in the two best TTR quartiles, and highest in the poorest TTR group. Mortality was higher for dabigatran, rivaroxaban, and apixaban, compared with the second best TTR quartile of warfarin. Conclusion DOACs with reduced doses are efficient and safe stroke prevention therapy in high-risk patients with AF when compared with warfarin therapy of sufficient TTR. In this comparison, warfarin therapy of excellent TTR-quality was associated with the lowest risk of bleeding and mortality.
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Affiliation(s)
- Alex Luojus
- Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Mika Lehto
- Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
- Department of Internal Medicine, Jorvi Hospital, Helsinki and Uusimaa Hospital District, Espoo, Finland
| | - Olli Halminen
- Aalto University, Espoo, Finland
- University of Eastern Finland, Kuopio, Finland
| | | | - Mikko Niemi
- Department of Clinical Pharmacology and Individualized Drug Therapy Research Program, University of Helsinki, Helsinki, Finland
- Department of Clinical Pharmacology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland
| | - Konsta Teppo
- Turku University Hospital and University of Turku, Finland
| | | | | | - Jukka Putaala
- Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Miika Linna
- Aalto University, Espoo, Finland
- University of Eastern Finland, Kuopio, Finland
| | - Pirjo Mustonen
- Turku University Hospital and University of Turku, Finland
| | - Aapo Aro
- Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | | | - Gregory Yoke Hong Lip
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK
- Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Medical University of Bialystok, Bialystok, Poland
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Zhang YT, Liu JP, Zhao ZN, Gu HQ, Na YF, Zhang TQ, Dong M, Wan YH, Zeng M, Sun N, Wu C, Yang J. Inappropriate dosing of direct oral anticoagulants among very older inpatients with atrial fibrillation. BMC Geriatr 2025; 25:292. [PMID: 40301761 PMCID: PMC12039067 DOI: 10.1186/s12877-025-05960-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Accepted: 04/17/2025] [Indexed: 05/01/2025] Open
Abstract
Among very older patients with atrial fibrillation (AF), the frequency of inappropriate direct oral anticoagulant (DOAC) dosing, associated factors, and temporal trends in practice are unknown.This retrospective study included consecutive inpatients aged 80 years or older with a discharge diagnosis of atrial fibrillation who were prescribed DOACs at discharge from Beijing Hospital between January 2018 and August 2023. Patients were stratified into underdosed, overdosed, or recommended dosing groups. Logistic regression analysis was performed to identify risk factors associated with inappropriate dosing, and temporal trends were evaluated using the Cochran-Mantel-Haenszel test.Among 676 inpatients aged ≥ 80 years with AF (mean age 84.4 ± 3.5 years; 53.1% female) who were prescribed a DOAC at hospital discharge (22.9% dabigatran, 62.3% rivaroxaban, 14.8% edoxaban), recommended dosing was observed in 338 patients (50.6%), underdosing in 308 (45.6%), and overdosing in 30 (4.4%). The overall rate of inappropriate dosing was 49.4%. Factors independently associated with underdosing included advanced age (OR = 1.98, 95% CI: 1.52-2.60, p < 0.001), lower creatinine clearance (OR = 0.98, 95% CI: 0.97-0.99, p = 0.01), and discharge from non-internal medicine wards (OR = 2.15, 95% CI: 1.33-3.45, p = 0.002). Overdosing was associated with younger age (OR = 0.38, 95% CI: 0.19-0.75, p = 0.005). Although the proportion of recommended dosing increased over the study period, and inappropriate dosing showed a declining trend, these changes did not reach statistical significance.Inappropriate DOAC dosing, especially underdosing, remains common in very older AF inpatients. This issue persists despite years passing, emphasizing the need for patient-focused, collaborative AF management and thorough prognostic studies.
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Affiliation(s)
- Ya-Tong Zhang
- Department of Pharmacy, Institute of Geriatric Medicine, Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application (Beijing Hospital), Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Jun-Peng Liu
- Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No.1, Da Hua Road, Dongcheng District, Beijing, 100730, China.
| | - Zi-Nan Zhao
- Department of Pharmacy, Institute of Geriatric Medicine, Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application (Beijing Hospital), Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Hong-Qiu Gu
- Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Capital Medical University, Beijing, China
| | - Yi-Fan Na
- Department of Pharmacy, Institute of Geriatric Medicine, Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application (Beijing Hospital), Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Tian-Qi Zhang
- Department of Pharmacy, Institute of Geriatric Medicine, Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application (Beijing Hospital), Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Min Dong
- Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No.1, Da Hua Road, Dongcheng District, Beijing, 100730, China
| | - Yu-Hao Wan
- Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No.1, Da Hua Road, Dongcheng District, Beijing, 100730, China
| | - Min Zeng
- Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No.1, Da Hua Road, Dongcheng District, Beijing, 100730, China
| | - Ning Sun
- Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No.1, Da Hua Road, Dongcheng District, Beijing, 100730, China
| | - Cheng Wu
- Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No.1, Da Hua Road, Dongcheng District, Beijing, 100730, China
| | - Jiefu Yang
- Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No.1, Da Hua Road, Dongcheng District, Beijing, 100730, China
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Zhao S, Dai H, Chen J, Ni M, Peng W, Li X, Li F, Chen B, Cai H, Liu Y, Du S. Prevalence, risk characteristics, and prediction of low-dose edoxaban treatment in hospitalized patients: a multicenter, observational cohort study. Front Pharmacol 2025; 16:1427634. [PMID: 40356968 PMCID: PMC12066837 DOI: 10.3389/fphar.2025.1427634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Accepted: 04/08/2025] [Indexed: 05/15/2025] Open
Abstract
Background Treatment with a low-dose non-vitamin K antagonist oral anticoagulant (NOAC) is common among hospitalized patients, and a model to predict the need for such treatment would support individualized interventions. This study evaluated the prevalence of low-dose edoxaban treatment and developed and evaluated a model to predict low-dose administration of edoxaban among hospitalized patients. Methods This study included 1208 inpatients with non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE) who were treated with edoxaban. Univariate and multivariate analyses identified variables significantly associated with low-dose edoxaban therapy. Least absolute shrinkage and selection operator (LASSO) regression was used for data dimension reduction and selection of the best variables. A nomogram was built based on the predictive variables for easy visualization. Model performance was evaluated, and the model was further validated internally with 1000 bootstrap resamples. Results The prevalence of low-dosing edoxaban treatment was 65.98% (797/1208). The predictors of edoxaban included in the final nomogram were age, weight, surgery or operation, anticoagulation indication, the use of antiarrhythmic drugs, anemia, and bleeding history. The model showed good discrimination with an area under the curve value of 0.792. The Hosmer‒Lemeshow test showed that the model had satisfactory goodness of fit (χ2 = 10.757, P = 0.2158). The calibration curve showed good agreement between predicted and actual probabilities. Conclusion The developed predictive model for low-dose edoxaban use among hospitalized patients was built using seven readily available variables and showed good performance. This study provides an empirical basis for early detection and intervention using a low-dose NOAC.
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Affiliation(s)
- Shujuan Zhao
- Department of Pharmacy, Henan Provincial People’s Hospital, School of Clinical Medicine, People’s Hospital of Zhengzhou University, Henan University, Zhengzhou, Henan, China
| | - Hengfen Dai
- Department of Pharmacy, Affiliated Fuzhou First Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Jiaxin Chen
- Department of Pharmacy, Ningde Municipal Hospital Affiliated to Ningde Normal University, Ningde, Fujian, China
| | - Ming Ni
- Department of Clinical Pharmacy, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan, China
| | - Wenxing Peng
- Department of Pharmacy, Beijing Anzhen Hospital of Capital Medical University, Beijing, China
| | - Xiaoyu Li
- Department of Pharmacy, Central’s Hospital of Xinxiang, Xinxiang, Henan, China
| | - Fen Li
- Department of Pharmacy, The First People’s Hospital of Xinxiang, Xinxiang, Henan, China
| | - Boya Chen
- Department of Pharmacy, Henan Provincial People’s Hospital, School of Clinical Medicine, People’s Hospital of Zhengzhou University, Henan University, Zhengzhou, Henan, China
| | - Haixia Cai
- Department of Pharmacy, Henan Provincial People’s Hospital, School of Clinical Medicine, People’s Hospital of Zhengzhou University, Henan University, Zhengzhou, Henan, China
| | - Yinping Liu
- Department of Pharmacy, Henan Provincial People’s Hospital, School of Clinical Medicine, People’s Hospital of Zhengzhou University, Henan University, Zhengzhou, Henan, China
| | - Song Du
- Department of Cardiovascular Medicine, Henan Provincial People’s Hospital, School of Clinical Medicine, People’s Hospital of Zhengzhou University, Henan University, Zhengzhou, Henan, China
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Sablot D, Gaillard N, Belahsen F, Lamelo SR, Dumitrana A, Plantard C, Daghmouri MA, Chaouch MA. Direct oral anticoagulation versus no therapy or antiplatelet for stroke prevention in patients with atrial fibrillation and history of intracranial hemorrhage: a systematic review and meta-analysis. Front Med (Lausanne) 2025; 12:1570809. [PMID: 40351471 PMCID: PMC12062129 DOI: 10.3389/fmed.2025.1570809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Accepted: 04/10/2025] [Indexed: 05/14/2025] Open
Abstract
Background Patients with atrial fibrillation and a history of intracranial hemorrhage (ICH) face a dilemma when resuming anticoagulation therapy due to the risk of ICH recurrence versus the need for Ischemic stroke (IS) prevention. This study aims to evaluate the safety and efficacy of direct oral anticoagulants (DOAC) compared to no therapy or antiplatelets in these patients. Methods We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. Electronic searches were performed in multiple databases (Cochrane, PubMed, Web of Science, Embase, Google Scholar, Scopus) up to March 1, 2024. We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs) involving patients with atrial fibrillation and prior ICH. Studies compared the group with no therapy or antiplatelets (no-DOAC group). Outcomes assessed included mortality, IS, ICH recurrence, and major bleeding events. Results Fifteen studies (8,318 patients) met the inclusion criteria, including 2,226 patients in the DOAC group and 5,936 in the no-OAC group. The major cardiovascular ischemic event was significantly lower in the DOAC group [OR = 0.11; CI 95% (0.03, 0.45); p = 0.002]. Ischemic stroke was lower in the DOAC group [OR = 0.53, 95% CI (0.39-0.72), p < 0.001]. There was no difference in ICH recurrence [OR = 1.25, 95% CI (0.28-5.71), p = 0.77] or major bleeding [OR = 0.63, 95% CI (0.23-1.72), p = 0.36]. Mortality rates were similar between groups [OR = 0.75, 95% CI (0.50-1.11), p = 0.15], while Heterogeneity was low for most outcomes. Conclusion DOACs appear to reduce the risk of IS without increasing mortality or major bleeding in patients with atrial fibrillation and prior ICH. However, the risk of ICH recurrence remains uncertain. These findings suggest a potential role for DOACs in this high-risk population, but further RCTs are needed to confirm these results. Systematic review registration Identifier CRD42024587511.
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Affiliation(s)
- Denis Sablot
- Neurology Department of Perpignan Hospital, Perpignan, France
- Commission of Clinical Research and Innovation, Perpignan, France
- Regional Health Agency of Occitanie, Montpellier, France
| | | | - Faouzi Belahsen
- Neurology Department, University Hospital Hassan II, University of Fes, Fes, Morocco
| | - Sara Rivas Lamelo
- Neurology Department of Perpignan Hospital, Perpignan, France
- Commission of Clinical Research and Innovation, Perpignan, France
| | | | - Carole Plantard
- Neurology Department of Perpignan Hospital, Perpignan, France
- Commission of Clinical Research and Innovation, Perpignan, France
| | | | - Mohamed Ali Chaouch
- Commission of Clinical Research and Innovation, Perpignan, France
- Department of Visceral and Digestive Surgery, Monastir University Hospital, University of Monastir, Monastir, Tunisia
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Miceli G, Ciaccio AM, Tuttolomondo A. Challenges and Opportunities of Direct Oral Anticoagulant (DOAC) Therapy in Complex Clinical Scenarios: A Comprehensive Review and Practical Guide. J Clin Med 2025; 14:2914. [PMID: 40363949 PMCID: PMC12072619 DOI: 10.3390/jcm14092914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2025] [Revised: 04/07/2025] [Accepted: 04/18/2025] [Indexed: 05/15/2025] Open
Abstract
Direct oral anticoagulants (DOACs) have emerged as a preferred alternative to vitamin K antagonists (VKAs) for the prevention and treatment of thromboembolic disorders, offering improved safety, predictable pharmacokinetics, and ease of administration. Despite these advantages, their use in complex clinical scenarios presents significant challenges that necessitate individualized therapeutic strategies. This comprehensive review explores the efficacy, safety, and limitations of DOAC therapy in special populations, including patients with renal or hepatic impairment, obesity, cancer-associated thrombosis, and antiphospholipid syndrome. Additionally, we examine their role in uncommon thrombotic conditions such as superficial venous thrombosis, embolic stroke of undetermined source, upper extremity vein thrombosis, inferior vena cava thrombosis, pelvic vein thrombosis, and cerebral vein thrombosis. The pharmacokinetic variability of DOACs in renal and hepatic dysfunction requires caution to balance the bleeding and thrombotic risks. In obesity, altered drug distribution and metabolism raise concerns regarding appropriate dosing and therapeutic efficacy. Cancer-associated thrombosis presents a complex interplay of prothrombotic mechanisms, necessitating careful selection of anticoagulant therapy. Furthermore, the use of DOACs in antiphospholipid syndrome remains controversial due to concerns about recurrent thrombotic events. Finally, in some unusual scenarios like inferior vena cava, pelvic vein, and cerebral vein thrombosis, the use of DOACs has scarce evidence. This review aims to guide clinicians in optimizing anticoagulation management in challenging patient populations by synthesizing current evidence and providing practical recommendations.
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Affiliation(s)
- Giuseppe Miceli
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE) Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90100 Palermo, Italy
| | - Anna Maria Ciaccio
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE) Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90100 Palermo, Italy
| | - Antonino Tuttolomondo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE) Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy
- Internal Medicine and Stroke Care Ward, University Hospital, Policlinico “P. Giaccone”, 90100 Palermo, Italy
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Wang X, Zhang C, Pan MM, Lin HW, Xue S, Xie B, Gu ZC. Design and rationale of the multicenter randomized clinical trial (REVERSE): Efficacy and safety of rivaroxaban in the early postoperative period for patients with bioprosthetic valve replacement or valve repair. Int J Cardiol 2025; 425:133023. [PMID: 39900192 DOI: 10.1016/j.ijcard.2025.133023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 01/09/2025] [Accepted: 01/28/2025] [Indexed: 02/05/2025]
Abstract
BACKGROUND Rivaroxaban, a Non-vitamin K oral anticoagulant (NOAC), is extensively employed for patients at heightened risk of thrombosis, including those with non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE). However, to date, there is a lack of robust clinical data to explore the efficacy and safety of rivaroxaban in thromboprophylaxis during the early postoperative period (<6 months) in patients following surgical bioprosthetic valve (BPV). METHODS The REVERSE trial is a prospective, multicenter, non-inferior, randomized controlled trial enrolling a planned 250 patients in China. Patients are randomly assigned 1:1 to receive rivaroxaban (20 mg once daily) or dose-adjusted warfarin (target international normalized ratio 2.0-3.0) for 6 months. The primary outcome is defined as the composite of all-cause death, major cardiovascular events, or major bleeding. The safety outcome is all bleeding events defined by the International Society on Thrombosis and Haemostasis (ISTH). CONCLUSIONS The REVERSE trial stands as the inaugural multicenter study dedicated to evaluating the efficacy and safety of rivaroxaban for early postoperative anticoagulation in BPV surgery patients. Its findings are anticipated to contribute pivotal evidence regarding the clinical advantages of NOACs. REGISTRATION URL: https://www. CLINICALTRIALS gov; Unique identifier: NCT06476301.
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Affiliation(s)
- Xin Wang
- Department of Pharmacy, Punan Branch of Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China; Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; College of Clinical Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
| | - Chi Zhang
- Department of Pharmacy, Punan Branch of Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China; Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; College of Clinical Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; School of Medicine, Tongji University, Shanghai 200092, China
| | - Mang-Mang Pan
- Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; College of Clinical Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
| | - Hou-Wen Lin
- Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; College of Clinical Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
| | - Song Xue
- Department of Cardiovascular Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
| | - Bo Xie
- Department of Cardiovascular Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
| | - Zhi-Chun Gu
- Department of Pharmacy, Punan Branch of Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China; Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; College of Clinical Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
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Vrtal J, Plasek J, Vaclavik J, Dodulik J, Sipula D. Anticoagulation in device-detected atrial fibrillation: Challenges in stroke prevention and heart failure management. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2025. [PMID: 40241616 DOI: 10.5507/bp.2025.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/18/2025] Open
Abstract
Atrial fibrillation (AF), the most common cardiac arrhythmia globally, contributes significantly to morbidity and mortality. With advancements in implantable devices like pacemakers, defibrillators, and loop recorders, incidental detection of AF as device-detected AF (DDAF) or subclinical AF (SCAF) has become common. This asymptomatic AF presents unique management challenges, particularly in anticoagulation decisions for stroke prevention. Evidence from recent trials, notably NOAH-AFNET 6 and ARTESiA, indicates a complex risk-benefit profile for anticoagulation in DDAF. In ARTESiA, anticoagulation modestly reduced stroke and systemic embolism rates, though this effect did not reach statistical significance. The NOAH-AFNET 6 trial found no significant reduction in a composite of cardiovascular death, stroke, or systemic embolism with anticoagulation compared to placebo. Both trials revealed an increased bleeding risk, underscoring the need to carefully weigh stroke prevention against bleeding risks in DDAF. The 2024 European Society of Cardiology guidelines reflect this nuanced approach by advocating a tailored, risk-based strategy. Emerging evidence also shows that AF burden impacts heart failure (HF) outcomes, with a five-fold increase in HF hospitalizations associated with higher AF burden. This highlights the importance of rhythm or rate control to reduce HF progression, particularly in patients with both AF and HF, where reducing AF burden is associated with better prognosis and fewer hospitalizations. Future research should focus on refining anticoagulation strategies, especially for patients with low AF burden, and exploring novel approaches like intermittent anticoagulation and advanced monitoring to support personalized DDAF management.
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Affiliation(s)
- Jiri Vrtal
- Department of Cardiology, University Hospital Ostrava, Ostrava, Czech Republic
| | - Jiri Plasek
- Department of Cardiology, University Hospital Ostrava, Ostrava, Czech Republic
- Research Center for Internal and Cardiovascular Diseases Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
| | - Jan Vaclavik
- Department of Cardiology, University Hospital Ostrava, Ostrava, Czech Republic
- Research Center for Internal and Cardiovascular Diseases Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
| | - Jozef Dodulik
- Department of Cardiology, University Hospital Ostrava, Ostrava, Czech Republic
| | - David Sipula
- Department of Cardiology, University Hospital Ostrava, Ostrava, Czech Republic
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Lenard A, Hermann SA, Stoll F, Burhenne J, Foerster KI, Czock D, Mikus G, Meid AD, Haefeli WE, Blank A. Effect of the frequently used antiepileptic drugs carbamazepine, gabapentin, and pregabalin on the pharmacokinetics of edoxaban and other oral factor xa inhibitors in healthy volunteers. Front Pharmacol 2025; 16:1542063. [PMID: 40290437 PMCID: PMC12022901 DOI: 10.3389/fphar.2025.1542063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 03/11/2025] [Indexed: 04/30/2025] Open
Abstract
Purpose Pregabalin, gabapentin, and carbamazepine, a potent inducer of cytochrome P450 (CYP) 3A4 and P-glycoprotein, are frequently used antiepileptic drugs that are often administered together with factor Xa inhibitors (FXaI). We aimed to investigate whether potentially clinically relevant drug-drug interactions occur with these combinations. Methods In an open-label fixed-sequence trial in 36 healthy volunteers, we evaluated the pharmacokinetics of 60 mg edoxaban and of a microdosed FXaI cocktail (25 µg apixaban, 50 µg edoxaban, and 25 µg rivaroxaban) before and during treatment with carbamazepine (12 evaluable volunteers, individually dosed to therapeutic concentrations), gabapentin (11 volunteers, titrated to 3 × 400 mg/d), and pregabalin (12 volunteers, titrated to 2 × 300 mg/d). The antiepileptics were dosed to steady-state and the CYP3A activity was evaluated by assessing the pharmacokinetics of microdosed midazolam (30 µg). Results Carbamazepine reduced the area under the plasma concentration-time curve (AUC ∞ ) of 60 mg edoxaban by a factor of 0.48 (geometric mean ratio (GMR) with 90% CI (0.41-0.56); p < 0.0001) and Cmax by a factor of 0.47 (0.34-0.66) and reduced the exposure of the edoxaban metabolite M-4 to a similar extent. Carbamazepine also decreased the exposure (AUC ∞ ) of microdosed apixaban, edoxaban, and rivaroxaban by a factor of 0.66, 0.59, and 0.56, respectively. Gabapentin and pregabalin did neither affect the exposure of 60 mg edoxaban nor the exposure of any microdosed FXaI. Conclusion Carbamazepine decreased FXaI exposure to a clinically relevant extent and dose adjustment may be required to maintain an adequate anticoagulant effect, whereas gabapentin and pregabalin do not require dose adjustment of FXaI.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Antje Blank
- Internal Medicine IX, Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University, Medical Faculty Heidelberg/Heidelberg University Hospital, Heidelberg, Germany
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Zhang H, Li M, Liu W, Yuan H. Dementia-related adverse events associated with direct oral anticoagulants use: a real-world, pharmacovigilance study based on the FAERS database. Expert Opin Drug Saf 2025:1-10. [PMID: 40207729 DOI: 10.1080/14740338.2025.2490847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Accepted: 03/05/2025] [Indexed: 04/11/2025]
Abstract
BACKGROUND Direct oral anticoagulants (DOACs) are commonly used to prevent and treat thromboembolic diseases. This study aimed to assess and compare dementia related adverse events (AEs) associated with DOACs. RESEARCH DESIGN AND METHODS AEs related to DOACs from January 2014 to June 2023 were extracted from the FDA Adverse Event Reporting System (FAERS) database. Disproportionality analysis methods, including reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Multi-Item Gamma Poisson Shrinker, were used to evaluate the association between DOACs and dementia-related AEs. RESULTS There were 12,692,968 AEs reported in FAERS after deduplication. Among these, 165, 206, 1574, and 12 dementia-related AEs that were attributed to dabigatran, rivaroxaban, apixaban, and edoxaban, respectively. Apixaban showed the strongest association with dementia-related AEs (ROR 7.66, 95% confidence interval (CI) 7.27-8.06), while rivaroxaban had the lowest ROR (0.95, 95%CI 0.83-1.09). Women exhibited higher RORs for all DOACs, with apixaban showing the most significant correlation. Subgroup analysis indicated a significant link between apixaban and dementia, dementia Alzheimer's type and senile dementia. CONCLUSIONS Apixaban appears most associated with dementia-related AEs among DOACs, whereas rivaroxaban poses a lower risk. Further research is needed to validate these findings through large-scale prospective studies.
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Affiliation(s)
- Hanxu Zhang
- Department of Pharmacy, Tianjin Medical University General Hospital, Tianjin, China
| | - Mengya Li
- Department of Pharmacy, Beijing You'an Hospital, Capital Medical University, Beijing, China
| | - Wei Liu
- Department of Pharmacy, Beijing You'an Hospital, Capital Medical University, Beijing, China
| | - Hengjie Yuan
- Department of Pharmacy, Tianjin Medical University General Hospital, Tianjin, China
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Qi F, Wu J, Xia Z, Xie S, Chen X, Zheng H, Li Z, Bao N, Li C, Xiao H. Clinical characteristics, adherence to anticoagulation therapy and prognosis in patients with atrial fibrillation: a real-life study. BMC Cardiovasc Disord 2025; 25:263. [PMID: 40189518 PMCID: PMC11974184 DOI: 10.1186/s12872-025-04703-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2025] [Accepted: 03/24/2025] [Indexed: 04/09/2025] Open
Abstract
BACKGROUND Atrial fibrillation (AF) is a prevalent tachyarrhythmia, and a comprehensive understanding of its clinical features is essential for optimizing therapeutic management. However, the unregulated use of anticoagulants in AF remains a concern, as their efficacy and safety profiles are not yet fully understood. METHODS Data from AF patients were collected in 2013, 2018, and 2023. First, cross-sectional data on AF patients were gathered during each period to longitudinally evaluate long-term trends in AF characteristics and the progression of anticoagulation therapy. Additionally, predictors of non-regulated dosing of oral anticoagulants (OAC) were analyzed. Second, patients with non-valvular atrial fibrillation (NVAF) were prospectively followed for 24 and 60 months with different NOAC doses to assess the risk of clinical outcome events and to analyze independent risk factors for clinical outcomes. RESULTS This study included 2825 AF patients, with 394 patients undergoing longitudinal follow-up. Paroxysmal AF (49.70%) and non-valvular atrial fibrillation (NVAF) (86.30%) were the most prevalent forms with advanced age being a prominent characteristic. Independent predictors of unregulated NOAC use included age, renal insufficiency, BMI, diabetes, hypertension, and bleeding risk. At the 24-month follow-up, patients who received overdosed NOAC exhibited a higher mortality rate compared to those who were inappropriately underdosed (18.75 vs.10.92 events/patient-year, P = 0.017). At the 60-month follow-up, both all-cause mortality (10.00 vs. 6.49 events per patient-year, P = 0.019; 10.00 vs. 6.21 events per patient-year, P = 0.005) and the composite endpoint event rate (12.50 vs. 9.61 events per patient-year, P = 0.017; 12.50 vs. 9.32 events per patient-year, P = 0.013) were significantly higher in the overdosing group compared to standard and underdosing groups. Age and anemia were identified as risk factors for all-cause mortality, while renal insufficiency was associated with an increased risk of composite endpoint events. CONCLUSION AF remains a major disease burden, especially in elderly patients. For Asians, NOAC underdosing was still effective in preventing stroke, but its efficacy and safety need to be further validated through larger-scale clinical trials. Meanwhile, overdosing of NOAC should be avoided. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Fenglin Qi
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - JiaCan Wu
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhen Xia
- Department of Cardiology, Chongqing Hechuan District People's Hospital, Chongqing, China
| | - Siyuan Xie
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xianya Chen
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Huanjie Zheng
- Department of Cardiology, Chengdu Second People's Hospital, Chengdu, China
| | - Zhuo Li
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Naiyue Bao
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Chengcheng Li
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hua Xiao
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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Atwater BD, Singh R, Parmar S, Ogbonnaya A, Kang A, Atreja N, Russ C, Cheng D, Hagan M, Deeba S, Hines DM. Geographic and Racial Variation in Oral Anticoagulant (OAC) Treatment Among Commercially Insured Patients with Non-valvular Atrial Fibrillation (NVAF) in the United States. Am J Cardiovasc Drugs 2025:10.1007/s40256-025-00728-x. [PMID: 40178719 DOI: 10.1007/s40256-025-00728-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/03/2025] [Indexed: 04/05/2025]
Abstract
BACKGROUND Oral anticoagulants (OACs) are recommended for stroke reduction in non-valvular atrial fibrillation (NVAF). OAC use has been studied in Medicare populations, but data for younger, commercially insured populations are limited. OBJECTIVE This retrospective study aimed to describe the geographic variation of OAC use among commercially insured patients with NVAF at high risk of stroke (CHA2DS2-VASc score ≥ 2) in the USA. METHODS Geographic variation was assessed by 3-digit zip code and race among patients identified from the Komodo Health commercial database with a diagnosis of NVAF between January 1, 2016, and August 31, 2021. Continuous health plan enrollment for ≥ 12 months before and 12 months after the NVAF diagnosis was required. RESULTS A total of 619,111 patients with NVAF at high risk for stroke were identified, of whom approximately 50% were not treated with OACs. Of the half who received OACs, almost 85% received direct OACs (DOACs) and 15% received warfarin therapy. Overall, the highest untreated rates were observed in the South and West US regions, followed by the Midwest, then the Northeast. The highest DOAC treatment rates were in the Northeast for White patients and in the North and South for Black patients. The highest warfarin treatment rates were in the upper Midwest for White patients and the Midwest for Black patients. CONCLUSIONS This study may help guide the identification of areas to target interventions to improve treatment rates and confirm prior findings of geographic and racial variations of OAC use in NVAF.
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Affiliation(s)
| | | | | | | | - Amiee Kang
- Bristol Myers Squibb, Lawrenceville, NJ, USA
| | | | | | - Dong Cheng
- Bristol Myers Squibb, Lawrenceville, NJ, USA
| | | | - Serina Deeba
- Pfizer, 66 Hudson Yards, New York, NY, 10001, USA
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Parry-Jones AR, Moullaali TJ, Sandset EC, Qureshi AI, Anderson CS, Steiner T. Importance of blood pressure lowering in patients with direct oral anticoagulant-associated intracerebral haemorrhage in the acute phase and for secondary prevention. Eur Stroke J 2025; 10:46-55. [PMID: 40401654 PMCID: PMC12099125 DOI: 10.1177/23969873231208544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 10/02/2023] [Indexed: 05/23/2025] Open
Abstract
PURPOSE Intracerebral haemorrhage (ICH) is an important complication of direct oral anticoagulation (DOAC) therapy, where risks and prognosis are potentially modified by effective blood pressure (BP) control, both in the acute phase and for secondary prevention. Herein, we review BP management in the context of general anticoagulation associated ICH and specifically in DOAC-ICH, considering current evidence and highlighting outstanding questions. METHOD Narrative review. FINDINGS Pooled analyses of major trials of BP lowering in acute ICH patients without anticoagulants demonstrate a reduction in the risk of haematoma expansion. As anticoagulant-associated ICH patients tend to be older, have more co-morbidities, and larger haematomas at baseline with a greater risk of expansion, the risks and benefits of intensive BP lowering treatment might both be higher. Small observational studies of DOAC-ICH patients suggest that lower achieved BP is associated with less expansion, lower mortality, and better functional outcomes. Care bundles including both anticoagulant reversal and intensive BP lowering might reduce the risk of death and disability in DOAC-ICH. Optimal control of BP in survivors of ICH reduces the risk of both ischaemic and haemorrhagic stroke but whether this modulates the risks and benefits of restarting a DOAC is unknown. DISCUSSION Limited evidence suggests that BP should be well managed in DOAC-ICH patients, in the same way as ICH patients not on anticoagulants, both in the hyperacute phase and for secondary prevention. Hypothetical differences in the effects of BP lowering treatment in DOAC-ICH need to be tested in clinical trials.
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Affiliation(s)
- Adrian R Parry-Jones
- Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance & University of Manchester, Manchester, UK
- Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Tom J Moullaali
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
- Department of Clinical Neurosciences, NHS Lothian, Edinburgh, UK
| | - Else C Sandset
- Department of Neurology, Stroke Unit, Oslo University Hospital, Oslo, Norway
- The Norwegian Air Ambulance Foundation, Oslo, Norway
| | - Adnan I Qureshi
- Zeenat Qureshi Stroke Institute and Department of Neurology, University of Missouri, Columbia, MO, USA
| | - Craig S Anderson
- The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia
- The George Institute China, Beijing, P.R. China
- Neurology Department, Royal Prince Alfred Hospital, Sydney Health Partners, Sydney, NSW, Australia
| | - Thorsten Steiner
- Departments of Neurology, Klinikum Frankfurt Höchst and Heidelberg University Hospital, Frankfurt, Germany
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Seiffge D, Polymeris A, Pfeilschifter W, Apostolaki-Hansson T, Ip B, Kristoffersen ES, Kuramatsu JB, Siepen BM. Reversal of anticoagulation in patients with intracerebral haemorrhage related to oral anticoagulants: State of the evidence. Eur Stroke J 2025; 10:14-23. [PMID: 40401655 PMCID: PMC12098327 DOI: 10.1177/23969873241281477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 08/13/2024] [Indexed: 05/23/2025] Open
Abstract
PURPOSE About 20%-25% of all intracerebral haemorrhages are associated with oral anticoagulation therapy. Reflecting changings prescription patterns in the general population, the spectrum of oral anticoagulation-associated intracerebral haemorrhage has substantially changed in the last decade. In many European countries, direct oral anticoagulant-associated intracerebral haemorrhage is now more frequent than vitamin K antagonist-associated intracerebral haemorrhage. Outcome in patients with anticoagulation-associated intracerebral haemorrhage is poor, likely mediated by a high incidence of haematoma expansion. Reversal of anticoagulation is an essential part of current care pathways for hyperacute treatment of intracerebral haemorrhage aiming to limit haematoma expansion and thereby improving outcome. METHODS In this review, we summarise the latest evidence regarding reversal therapy for vitamin K antagonist-, direct thrombin inhibitor- and factor Xa inhibitor-associated intracerebral haemorrhage. FINDINGS Two randomised controlled trials have shown that the use of prothrombin complex concentrate (compared to fresh frozen plasma) for reversing vitamin K antagonist-associated intracerebral haemorrhage and andexanet alfa (compared to usual care, mainly prothrombin complex concentrate) for factor Xa inhibitor-associated intracerebral haemorrhage had superior haemostatic efficacy. However, the incidence of thromboembolic complications was high in both trials. For reversal of Vitamin K antagonist-associated intracerebral haemorrhage, the overall rate was 18% but due to crossovers, it is impossible to determine the rate for any specific treatment. For factor-Xa inhibitor associated intracerebral haemorrhage, andexanet alfa led to an increase in the incidence of thromboembolic events. Moreover, these two randomised controlled trials were not powered to detect differences in mortality or functional outcomes and lacked long-term follow-up. Idarucizumab has shown promising results in a single-arm case series of patients with intracerebral haemorrhage associated with the direct thrombin inhibitor dabigatran, yet no randomised controlled trial is available to support these findings. CONCLUSION Given that haematoma expansion is strongly associated with poor outcome, current evidence underlines the importance of rapid, targeted and effective reversal of anticoagulation in patients with anticoagulation-associated intracerebral haemorrhage. While haematoma expansion is a key prognostic factor, no randomised controlled trial has demonstrated a clear improvement in functional outcome. Future research should weigh the advantages of preventing haematoma expansion against the risks of increased thromboembolic events, and aim to identify the patients who would derive the most benefit from reversal treatments.
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Affiliation(s)
- David Seiffge
- Department of Neurology, Inselspital University Hospital and University of Bern, Bern, Switzerland
| | - Alexandros Polymeris
- Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Waltraud Pfeilschifter
- Department of Neurology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
- Department of Neurology and Clinical Neurophysiology, Städtisches Klinikum Lüneburg, Lüneburg, Germany
| | | | - Bonaventure Ip
- Department of Medicine and Therapeutics, Faculty of Medicine, The Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR
- Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR
| | - Espen Saxhaug Kristoffersen
- Department of Neurology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway
- Department of General Practice, University of Oslo, Oslo, Norway
| | - Joji B Kuramatsu
- Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany
| | - Bernhard M Siepen
- Department of Neurology, Inselspital University Hospital and University of Bern, Bern, Switzerland
- Graduate School for Health Sciences, University of Bern, Bern, Switzerland
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40
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Christensen H, Casolla B, Frontera JA, Grundtvig J, Nielsen JD, Petersson J, Steiner T. Principles of reversal of anticoagulation in patients with intracerebral hemorrhage related to oral anticoagulants. Eur Stroke J 2025; 10:4-13. [PMID: 40401657 PMCID: PMC12098318 DOI: 10.1177/23969873231222393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 12/05/2023] [Indexed: 05/23/2025] Open
Abstract
The incidence of intracerebral hemorrhage (ICH) associated with oral anticoagulants (OAC) is about one in five cases of ICH and associated with severe clinical presentation, frequently rapid clinical deterioration, and 30-days mortality of app 50%. This narrative review gives an overview of presentation and acute treatment of OAC-ICH. Oral anticoagulants do not cause ICH but lead to prolongation of bleeding and higher risk of hematoma expansion (HE). Clinicoradiological characteristics of oral anticoagulant associated ICH are not different from ICH in general. The therapeutic principle of reversal is to prevent or limit HE. The mode of action of the reversal agents for vitamin K antagonists, direct oral thrombin inhibitor and direct oral factor Xa inhibitors are described in the main text. We also discuss the principles of blood pressure lowering in the setting of acute OAC-ICH as it may be the second driving force of HE. Stroke unit care is needed to prevent further complications. Data from randomized controlled trials and observational data from unselected patients are needed to make stronger and more precise recommendations on acute therapy.
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Affiliation(s)
- Hanne Christensen
- Department of Neurology, Bispebjerg-Frederiksberg University Hospital, Kobenhavn, Denmark
| | - Barbara Casolla
- Stroke Unit, CHU Pasteur 2, Université Cote d’Azur, UMR2CA URRIS), Nice, France
| | | | - Josefine Grundtvig
- Department of Neurology, Bispebjerg-Frederiksberg University Hospital, Kobenhavn, Denmark
| | - Jørn Dalsgaard Nielsen
- Centre for Excellence of Anticoagulant Therapy, Bispebjerg-Frederiksberg University Hospital, Frederiksberg, Denmark
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Mizuno K, Yokoyama J, Shibata O, Kojima Y, Kawata Y, Takahashi K, Tominaga K, Satoshi I, Kazunao H, Terai S. Safety of edoxaban for delayed bleeding in gastrointestinal endoscopic procedures with a high risk of bleeding. DEN OPEN 2025; 5:e70018. [PMID: 39372286 PMCID: PMC11450183 DOI: 10.1002/deo2.70018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 09/03/2024] [Accepted: 09/14/2024] [Indexed: 10/08/2024]
Abstract
Objectives There are limited reports on the safety of gastrointestinal endoscopic procedures in individuals taking edoxaban, one of the direct oral anticoagulants. We clarified the incidence of delayed bleeding in patients who were on edoxaban in the perioperative period of gastrointestinal endoscopic procedures with a high risk of bleeding. Methods This was an investigator-initiated, single-center, open-label, prospective, single-arm study. Patients on warfarin or edoxaban undergoing endoscopy with a high risk of bleeding were enrolled from June 2018 to September 2021. Warfarin was replaced with edoxaban in patients on warfarin. Patients taking other direct oral anticoagulants, and antiplatelet drugs, were excluded. The primary endpoint was severe delayed bleeding (Common Terminology Criteria for Adverse Events [CTCAE] grades III-V) and the secondary endpoints included thromboembolism, all adverse events, any delayed bleeding (CTCAE grades I or II), and hospital stay durations. Results Twenty-one patients on edoxaban underwent high-risk endoscopy. Three cases (14%) experienced CTCAE grade III delayed bleeding, requiring endoscopic hemostasis. No CTCAE grade I-II delayed bleeding or thromboembolic events occurred. Cholangitis and aspiration pneumonia (conservatively treated) occurred during the hospital stay. The median length of hospital stay was 8 days (range 3-24 days). Patients with delayed bleeding had higher systolic blood pressure at admission and longer hospital stays. Conclusions The delayed bleeding incidence in high-risk endoscopic procedures for patients on edoxaban was acceptable. Higher blood pressure may be associated with increased risk, but further research is needed.
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Affiliation(s)
- Ken‐ichi Mizuno
- Department of EndoscopyNiigata University Medical and Dental HospitalNiigataJapan
| | - Junji Yokoyama
- Department of GastroenterologySaiseikai Niigata HospitalNiigataJapan
| | - Osamu Shibata
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental ScienceNiigata UniversityNiigataJapan
| | - Yuichi Kojima
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental ScienceNiigata UniversityNiigataJapan
| | - Yuzo Kawata
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental ScienceNiigata UniversityNiigataJapan
| | - Kazuya Takahashi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental ScienceNiigata UniversityNiigataJapan
| | - Kentaro Tominaga
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental ScienceNiigata UniversityNiigataJapan
| | - Ikarasi Satoshi
- Department of EndoscopyNiigata University Medical and Dental HospitalNiigataJapan
| | - Hayashi Kazunao
- Department of EndoscopyNiigata University Medical and Dental HospitalNiigataJapan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental ScienceNiigata UniversityNiigataJapan
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Wolfes J, Ellermann C, Frommeyer G, Eckardt L. Comparison of the Latest ESC, ACC/AHA/ACCP/HRS, and CCS Guidelines on the Management of Atrial Fibrillation. JACC Clin Electrophysiol 2025; 11:836-849. [PMID: 39985521 DOI: 10.1016/j.jacep.2024.12.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 12/11/2024] [Accepted: 12/16/2024] [Indexed: 02/24/2025]
Abstract
The introduction of evidence-based and structured guidelines has undoubtedly improved the care of cardiologic patients and in many cases simplified decision-making for the treatment team. The European Society of Cardiology in collaboration with the European Association for Cardio-Thoracic Surgery, the American College of Cardiology, the American Heart Association, the American College of Clinical Pharmacy, and the Heart Rhythm Society, and the Canadian Cardiovascular Society/Canadian Heart Rhythm Society have developed guidelines for the management of patients with atrial fibrillation. Because all 3 guidelines refer to almost the same scientific data, their recommendations are undoubtedly largely in agreement. Nevertheless, there are some interesting differences based on different interpretations of the same study, different publication dates, or differences in local conditions and health care resources. The following article aims at lining out these similarities and differences.
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Affiliation(s)
- Julian Wolfes
- Department of Cardiology II (Electrophysiology), University Hospital Munster, Münster, Germany.
| | - Christian Ellermann
- Department of Cardiology II (Electrophysiology), University Hospital Munster, Münster, Germany
| | - Gerrit Frommeyer
- Department of Cardiology II (Electrophysiology), University Hospital Munster, Münster, Germany
| | - Lars Eckardt
- Department of Cardiology II (Electrophysiology), University Hospital Munster, Münster, Germany
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Yu CC, Peng YQ, Lin C, Chiang CH, Liu CM, Lin YJ, Lin LY, Lo MT. ECG-based machine learning model for AF identification in patients with first ischemic stroke. Int J Stroke 2025; 20:411-418. [PMID: 39533802 DOI: 10.1177/17474930241302272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
BACKGROUND The recurrence rate of strokes associated with atrial fibrillation (AF) can be substantially reduced through the administration of oral anticoagulants. However, previous studies have not demonstrated a clear benefit from the universal application of oral anticoagulants in patients with embolic stroke of undetermined source. Timely detection of AF remains a challenge in patients with stroke. AIM This study aims to develop a convolutional neural network (CNN) model to accurately identify patients with AF using a 12-lead sinus-rhythm electrocardiogram (ECG) recorded around the time of the first ischemic stroke. In addition, this study also evaluates the model's ability to predict future occurrence of AF. METHODS A CNN model was trained with ECG data from patients at Taipei Veterans General Hospital. External validation was performed on ischemic stroke patients from National Taiwan University Hospital. The model's performance was assessed for detecting AF at the stroke event and predicting future AF occurrences. RESULTS The model demonstrated an area under curve (AUC) of 0.91 for internal validation and 0.69 for external validation in identifying AF at the stroke event, with sensitivity and negative predictive value both achieving 97%. Kaplan-Meier survival analysis of patients without a prior diagnosis of AF revealed a significant increase in future AF incidence among the high-risk group identified by the model (adjusted hazard ratio: 4.06; 95% confidence interval: 2.74-6.00). CONCLUSIONS The CNN model effectively identifies AF in stroke patients using 12-lead ECGs and predicts future AF events, facilitating early anticoagulation therapy and potentially reducing recurrent stroke risk. Further prospective studies are warranted to confirm these findings.
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Affiliation(s)
- Chih-Chieh Yu
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei City
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei City
| | - Yu-Qi Peng
- Department of Biomedical Sciences and Engineering, National Central University, Taoyuan
| | - Chen Lin
- Department of Biomedical Sciences and Engineering, National Central University, Taoyuan
| | - Chia-Hsin Chiang
- Department of Biomedical Sciences and Engineering, National Central University, Taoyuan
- Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei City
- Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei City
| | - Chih-Min Liu
- Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei City
- Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei City
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei City
| | - Yenn-Jiang Lin
- Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei City
- Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei City
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei City
- Cardiovascular Center, Taichung Veterans General Hospital, Taichung
| | - Lian-Yu Lin
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei City
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei City
| | - Men-Tzung Lo
- Department of Biomedical Sciences and Engineering, National Central University, Taoyuan
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Fudim M, Lopes RD, Wojdyla DM, Mehran R, Khan MS, Granger CB, Goodman SG, Aronson R, Windecker S, Alexander JH. Apixaban Dose in Patients With Atrial Fibrillation and Acute Coronary Syndrome and/or Undergoing Percutaneous Coronary Intervention: Insights From AUGUSTUS. JACC. ADVANCES 2025; 4:101665. [PMID: 40117694 PMCID: PMC11976251 DOI: 10.1016/j.jacadv.2025.101665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 01/30/2025] [Accepted: 02/14/2025] [Indexed: 03/23/2025]
Abstract
BACKGROUND Studies have demonstrated the safety and efficacy of reducing the dose of apixaban from 5.0 mg to 2.5 mg twice daily in patients with atrial fibrillation (AF) and ≥2 dose-reduction criteria (age ≥80 years, body weight ≤60 kg, serum creatinine ≥1.5 mg/dL). However, data on reduced dose apixaban in patients with AF and acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI) are limited. OBJECTIVES The authors aimed to assess clinical outcomes, including bleeding and death/ischemic events, according to apixaban dose in AUGUSTUS. METHODS In AUGUSTUS, 4,614 patients with AF and/or recent ACS or PCI on a P2Y12 inhibitor were randomized to open-label apixaban or vitamin K antagonist (VKA) and blinded aspirin or placebo for 6 months. Apixaban dose was determined by investigators following the apixaban label. We assessed outcomes, including major/clinically relevant nonmajor bleeding and death/ischemic events, among patients who appropriately received reduced dose apixaban, inappropriately received reduced dose apixaban, and appropriately received standard dose apixaban compared with VKA. RESULTS Of 2,290 patients assigned apixaban, 229 (10%) received reduced dose apixaban and 98 (43%) of those met dose-reduction criteria. Among patients receiving appropriately reduced, inappropriately reduced, and standard dose apixaban, rates of major/clinically relevant nonmajor bleeding were 13.7%, 10.5%, and 11.0%; rates of death or ischemic events were 12.2%, 12.3%, and 5.7%. When comparing the risk of clinical outcomes in the 3 groups (appropriately reduced, inappropriately reduced, and standard dose apixaban) vs matched patients receiving VKA, we found that patients receiving apixaban had more favorable outcomes than those receiving VKA, without significant interaction (P > 0.20 across all 3 groups and all outcomes). CONCLUSIONS Of the ∼10% of patients in AUGUSTUS who received reduced dose apixaban, less than one-half met the dose-reduction criteria. In patients with AF and recent ACS or PCI, appropriately reduced dose apixaban was associated with a lower risk of bleeding and similar rates of ischemic outcomes compared with VKA, similar results were found with standard dose apixaban. (A Study of Apixaban in Patients With Atrial Fibrillation, Not Caused by a Heart Valve Problem, Who Are at Risk for Thrombosis [Blood Clots] Due to Having Had a Recent Coronary Event, Such as a Heart Attack or a Procedure to Open the Vessels of the Heart; NCT02415400).
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Affiliation(s)
- Marat Fudim
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
| | - Renato D Lopes
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA
| | - Daniel M Wojdyla
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA
| | - Roxana Mehran
- Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, and Cardiovascular Research Foundation, New York, New York, USA
| | - Muhammad Shahzeb Khan
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA
| | - Christopher B Granger
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA
| | - Shaun G Goodman
- Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada; Terrence Donnelly Heart Centre, St. Michael's Hospital, University of Toronto, Toronto, Canada
| | | | - Stephan Windecker
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA
| | - John H Alexander
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA
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Wuyts SCM, Moor JD, Jochmans K, Cortoos PJ, Vandervorst F, Steurbaut S, Dupont AG, Cornu P. Prescriptions of CYP3A4- and P-gp inducers for patients on direct oral anticoagulants: Bridging the gap between epidemiology and patient management for optimal thromboembolic event prevention. Br J Clin Pharmacol 2025; 91:1114-1131. [PMID: 39994875 DOI: 10.1002/bcp.70007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Revised: 01/15/2025] [Accepted: 01/28/2025] [Indexed: 02/26/2025] Open
Abstract
Direct oral anticoagulants (DOACs) are frequently used for the treatment and prevention of ischaemic stroke in patients with non-valvular atrial fibrillation. Compared to vitamin K antagonists, DOACs have significant advantages, although their drug-drug interaction (DDI) profile may complicate drug efficacy and safety. This narrative review addresses the clinical challenges posed by these DDIs and the potential pharmacological alternatives and monitoring strategies available. A PubMed search was conducted (1 January 2000-31 December 2023) including human DDI studies on DOAC use and CYP3A4/P-gp inducers in adult patients, evaluating patient outcome data and recommendations for DDI management. Twenty-two studies were included. Case reports (n = 6) indicated that antiepileptic drugs such as carbamazepine, phenobarbital and phenytoin may be associated with thromboembolic events. The nested case-control studies (n = 2) and cohort studies (n = 9) found that co-administration of DOACs and CYP3A4/P-gp inducers, particularly carbamazepine and phenytoin, increased the risk of thromboembolic events. Pharmacovigilance database analyses indicated a significant association between DOAC DDIs and increased reported stroke rates. Management recommendations in systematic reviews (n = 5) highlighted monitoring when DOACs were combined with inducers. Strategies included using alternative drugs with a weaker or preferentially absent inducing profile. Limited evidence suggests that edoxaban may be an acceptable option in case of DOAC and CYP3A4/P-gp inducer interactions; however, robust clinical data confirming safety are needed. Present literature indicates a higher thromboembolic risk in patients on DOAC treatment combining CYP3A4- and/or P-gp inducers. DOAC management should be tailored to the individual patient through collaboration between expert healthcare professionals.
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Affiliation(s)
- Stephanie C M Wuyts
- Pharmacy Department, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
- Research Centre for Digital Medicine, Vrije Universiteit Brussel (VUB), Brussels, Belgium
| | - Joris De Moor
- Department of Neurology, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
- NEUR Research Group, Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium
| | - Kristin Jochmans
- Department of Hematology, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
| | - Pieter-Jan Cortoos
- Pharmacy Department, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
- Vitality Research Group, Vrije Universiteit Brussel (VUB), Brussels, Belgium
| | - Fenne Vandervorst
- Department of Neurology, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
- NEUR Research Group, Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium
| | - Stephane Steurbaut
- Pharmacy Department, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
- Vitality Research Group, Vrije Universiteit Brussel (VUB), Brussels, Belgium
| | - Alain G Dupont
- Research Centre for Digital Medicine, Vrije Universiteit Brussel (VUB), Brussels, Belgium
| | - Pieter Cornu
- Research Centre for Digital Medicine, Vrije Universiteit Brussel (VUB), Brussels, Belgium
- Department of Information and Communication Technology, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
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Fácila L, Cordero A, Valverde Tavira A, Rilo Miranda I, Laskibar Asua A, Tirapu L, Montagud V, Sánchez-Serna J, Gómez-Mariscal E, Mainar L, Martín Dorado E, Lorenzo N, Pello Lázaro AM, Rodríguez-Mañero M. Characterization and anticoagulation treatment patterns of hospitalized patients with nonvalvular atrial fibrillation in Spain: The CARISMA registry. INTERNATIONAL JOURNAL OF CARDIOLOGY. HEART & VASCULATURE 2025; 57:101639. [PMID: 40104835 PMCID: PMC11914993 DOI: 10.1016/j.ijcha.2025.101639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 01/10/2025] [Accepted: 02/24/2025] [Indexed: 03/20/2025]
Abstract
Background This study described the clinical and demographic characteristics of hospitalized patients with nonvalvular atrial fibrillation (NVAF) and prescriptions for vitamin-K antagonists (VKA) and direct-acting oral anticoagulants (DOAC) in Spain. Methods This was an observational, multicentric, retrospective study of patients treated with DOAC or VKA due to NVAF at cardiology services of hospitals in Spain. A registry (CARISMA) included patients hospitalized for any reason and discharged before July 1st, 2021, with a prescription for DOAC or VKA. Data was collected on demographic and clinical characteristics and anticoagulant treatments prescribed. Analyses were descriptive. Results A total of 1,041 patients were included. Mean age (SD) was 77.2 (10.3) years and 57.6 % were men. The most frequent reason for hospital admission was heart failure (43.8 %) and arrhythmias (25.0 %). The mean (SD) CHA2DS2-VASc score was 4.0 (1.6). Prior to admission, 75.6 % of patients had been prescribed anticoagulant treatment for NVAF. Of these, 56.0 % had received VKA and 44.0 % DOAC. At discharge, 60 % had a DOAC prescription (of these, apixaban, 37.6 %; edoxaban, 26.4 %; rivaroxaban, 25.1 %; dabigatran, 10.9 %) and 40 % a VKA. DOAC prescriptions were off-label with respect to dosing in 19-34 % of cases. Patients with off-label dosing were older and with a higher proportion of women than those with on-label doses. During hospitalization, 12.1 % of patients changed treatment, usually VKA to DOAC. Conclusion Before hospitalization, a quarter of patients with NVAF were not receiving anticoagulation medication. Hospitalization increased the proportion of patients receiving DOAC, but about a quarter of patients had off-label dosing prescriptions.
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Affiliation(s)
- Lorenzo Fácila
- Department of Cardiology, Hospital General Universitario de Valencia, Valencia, Spain
- Faculty of Medicine, Universitat de Valencia, Valencia, Spain
| | | | | | - Irene Rilo Miranda
- Department of Cardiology, Hospital Universitario Donostia Nuestra Señora de Aranzazu, Donostia-San Sebastián, Spain
| | | | - Laia Tirapu
- Department of Cardiology, Hospital De Sant Joan Despí Moisés Broggi, Sant Joan Despí, Barcelona, Spain
| | - Vicente Montagud
- Department of Cardiology, Hospital General Universitario de Valencia, Valencia, Spain
| | - Juan Sánchez-Serna
- Department of Cardiology, Hospital de la Vega Lorenzo Guirao, Cieza, Murcia, Spain
| | - Eloy Gómez-Mariscal
- Department of Cardiology, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - Luis Mainar
- Department of Cardiology, Hospital de Manises, Valencia, Spain
| | | | - Natalia Lorenzo
- Department of Cardiology, Hospital Universitario Infanta Cristina, Madrid, Spain
| | | | - Moisés Rodríguez-Mañero
- Department of Cardiology, Complejo Hospital Universitario de Santiago, Santiago de Compostela, Spain
- Instituto de Investigación Sanitaria (IDIS), Universidad de Santiago de Compostela, Santiago de Compostela, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV CB16/11/00226-CB16/11/00420), Spain
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47
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Song J, Jaradeh M, Xu W, Deluna A, Sevak RJ, Wang C, Zhao SX. Pericardial Effusion Associated With Direct Oral Anticoagulant Use in a Single Center Experience. JACC. ADVANCES 2025; 4:101612. [PMID: 40280703 DOI: 10.1016/j.jacadv.2025.101612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 12/18/2024] [Accepted: 12/31/2024] [Indexed: 04/29/2025]
Abstract
BACKGROUND Pericardial effusion (PEff) has been described to occur in association with direct oral anticoagulant (DOAC). OBJECTIVES The purpose of this study was to assess the incidence, characteristics, and predisposing factors of PEff associated with DOACs. METHODS In this retrospective single center study, multivariable logistic regression analysis was used to identify factors associated with PEff in adult patients (age ≥18 years) in the Santa Clara Health System between 2013 and 2023. RESULTS Of the 456 patients with at least small to moderate PEff, 50 were on DOACs (DOAC PEff), 16 on warfarin (warfarin PEff), and 390 with no anticoagulation (NA PEff), with annual incidence 0.069%, 0.047%, and 0.001% for DOAC, warfarin, and NA PEff, respectively. Twenty-five (50%) of the DOAC PEff cases had moderately large or large PEff. Twenty-one cases underwent either percutaneous or surgical drainage. The DOAC PEff patients were significantly older and with more concurrent use of amiodarone. Logistic regression identified the following factors associated with moderately large or large PEff: DOAC (OR: 2.28; 95% CI: 1.19-4.37), warfarin (OR: 5.50; 95% CI: 1.88-16.06), concurrent use of amiodarone (OR: 4.32; 95% CI: 1.46-12.78), and presence of solid tumor (OR: 2.06; 95% CI: 1.25-3.39). CONCLUSIONS This is the largest single center case series of DOAC PEff, with annual incidence higher than previously reported. Future research is needed to study the pharmacokinetic interactions between DOACs and commonly co-prescribed drugs as well as the cost-effectiveness of enhanced surveillance of PEff in those with solid cancer while on DOACs.
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Affiliation(s)
- Jessica Song
- Department of Pharmacy Practice, University of the Pacific School of Pharmacy, PHS 299, Stockton, California, USA
| | - Mark Jaradeh
- Department of Medicine, Santa Clara Valley Medical Center, San Jose, California, USA
| | | | - Andres Deluna
- Division of Cardiology, Santa Clara Valley Medical Center, San Jose, California, USA
| | - Rajkumar J Sevak
- Department of Pharmacy Practice, University of the Pacific School of Pharmacy, PHS 299, Stockton, California, USA
| | - Clifford Wang
- Department of Medicine, Santa Clara Valley Medical Center, San Jose, California, USA
| | - Susan X Zhao
- Division of Cardiology, Santa Clara Valley Medical Center, San Jose, California, USA.
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48
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Carbone A, Bottino R, Attena E, Parisi V, Conte M, D'Andrea A, Imbalzano E, Alfredo C, Russo V. Oral Anticoagulation for Atrial Fibrillation in Octogenarians Across the Renal Function Spectrum. Cardiovasc Drugs Ther 2025; 39:317-324. [PMID: 38108919 DOI: 10.1007/s10557-023-07539-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/08/2023] [Indexed: 12/19/2023]
Abstract
PURPOSE Our study aimed to describe the efficacy and safety of oral anticoagulation (OAC) use in octogenarians with atrial fibrillation (AF) across the spectrum of renal function. METHODS Data for this study were sourced from AF Research Database (NCT03760874). AF patients aged ≥ 80 who received OAC treatment, both direct oral anticoagulant (DOAC) and vitamin K antagonist (VKA) were selected. Participants were categorized in 2 groups according to creatinine clearance (CrCl) ≥ 45 and < 45 ml/min/1.73 m2. The primary safety outcome was the occurrence major bleeding. The primary effectiveness outcome was the occurrence of thromboembolic events. RESULTS A total of 901 AF patients (median age 84 [4.9] years; 44% men) with age ≥ 80 years on treatment with DOACs (n: 629, 70%) and VKA (n: 272, 30%) were included in the study. 303 patients (34%) had CrCl < 45 ml/min/1.73m2 and 598 (66%) had CrCl ≥ 45 ml/min/1.73m2. No significant differences were shown in major bleedings, minor bleedings and thromboembolic events between patients on DOACs vs VKAs, both in the group with CrCl ≥ 45 than < 45 ml/min. In the group with CrCl < 45 ml/min/1.73 m2, a total of 72 patients (23%) died during the follow-up, with higher mortality in VKA group compared to DOACs (45% vs 15%; p < 0.001). At multivariate regression analysis, age [OR: 1.15; p = 0.001] and coronary artery disease (CAD) [OR: 1.74; p = 0.04] were independently associated with mortality; in contrast, the use of DOACs were inversely associated with mortality [OR = 0.26; p < 0.001]. In patients with CrCl ≥ 45 ml/min/1.73 m2, DOACs group experienced less intra-cranial hemorrhage (ICH) (0.2% vs 2.8%; p = 0.01) compared to VKAs. VKAs patients showed higher mortality compared to those on DOACs (29.1% vs 7.9%; p < 0.001). At multivariate regression analysis, chronic heart failure [OR = 2.14; p = 0.01] was independently associated with death, whereas male gender [OR: 0.45; p = 0.009] and the use of DOACs [OR: 0.29; p < 0.001] were associated with lower mortality. CONCLUSION DOACs seem to be safe and effective in octogenarians with chronic kidney disease at stage ≥ G3b. As compared with VKA administration, the use of DOACs was associated with lower mortality rates among AF octogenarians with renal dysfunction.
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Affiliation(s)
- Andreina Carbone
- Cardiology Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Napoli, Italy.
| | - Roberta Bottino
- Cardiology Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Napoli, Italy
| | - Emilio Attena
- Cardiology Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli" - Naples, Naples, Italy
| | - Valentina Parisi
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Maddalena Conte
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Antonello D'Andrea
- Unit of Cardiology and Intensive Coronary Care, Umberto I Hospital, Nocera Inferiore, Italy
| | - Egidio Imbalzano
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Caturano Alfredo
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Vincenzo Russo
- Cardiology Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli" - Naples, Naples, Italy
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49
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Carlin S, Chan N, Godoy A, Bhagirath V, Hirsh J, Eikelboom J. Choosing the optimal oral anticoagulant for stroke prevention in atrial fibrillation: direct oral anticoagulants vs vitamin K antagonists. J Thromb Haemost 2025; 23:1207-1214. [PMID: 39581233 DOI: 10.1016/j.jtha.2024.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 10/29/2024] [Accepted: 11/04/2024] [Indexed: 11/26/2024]
Abstract
Direct oral anticoagulants (DOACs) have replaced vitamin K antagonists (VKAs) for stroke prevention in many patients with atrial fibrillation, but VKAs may still be preferred in some situations. We use a case-based approach to present the evidence for the possible use of a VKA in preference to a DOAC in patients with atrial fibrillation and rheumatic mitral stenosis, high body mass index, frailty, and breakthrough stroke despite being prescribed a DOAC.
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Affiliation(s)
- Stephanie Carlin
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada.
| | - Noel Chan
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada; Population Health Research Institute, Hamilton, Ontario, Canada
| | - Alejandro Godoy
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Population Health Research Institute, Hamilton, Ontario, Canada
| | - Vinai Bhagirath
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada; Population Health Research Institute, Hamilton, Ontario, Canada
| | - Jack Hirsh
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - John Eikelboom
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Population Health Research Institute, Hamilton, Ontario, Canada
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50
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Izumi-Tamura T, Takano K, Nagao S, Tachi N, Sato S, Nakagawa M, Sone T, Takada K, Ogata H, Saito K, Kato S, Maekawa T, Yoshimi A, Kobayashi S, Kimura F. Proinflammatory and prothrombotic conditions in JAK2V617F-positive MPN: a case of Lemierre's syndrome in essential thrombocythemia. Ann Hematol 2025; 104:2563-2570. [PMID: 40107997 PMCID: PMC12053345 DOI: 10.1007/s00277-025-06234-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 01/27/2025] [Indexed: 03/22/2025]
Abstract
Lemierre's syndrome (LS) represents a rare yet potentially life-threatening systemic infection, characterized by thrombophlebitis of the internal jugular vein and abscess formation in distant organs. It typically follows episodes of tonsillitis or other infections of the oropharyngeal region. Pulmonary complications, including septic pulmonary emboli, are common. Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) sometimes associated with the JAK2V617F mutation, which predisposes patients to thrombotic events. A 66-year-old male with JAK2V617F-positive ET presented with severe pulsatile pain radiating from the right temporal region to the occipital area following a recent dental infection. Although pain management was administered, the pain continued to persist. Computed tomography of the chest revealed multiple subpleural nodules, raising suspicion for septic pulmonary emboli. Further investigation with gadolinium-enhanced magnetic resonance imaging identified a thrombus extending from the right sigmoid sinus into the internal jugular vein, consistent with cerebral venous thrombosis. The patient was diagnosed with LS, complicated by septic thrombosis. Blood cultures yielded alpha-hemolytic streptococcus. Empirical antimicrobial therapy combined with anticoagulation was initiated, resulting in a gradual improvement of symptoms, including the resolution of fever and pain. Follow-up imaging confirmed the resolution of both the infection and thrombosis. This is the first reported case of LS in a patient with JAK2V617F-positive ET. The coexistence of LS and JAK2V617F-positive MPN highlights the potential interplay between proinflammatory and prothrombotic conditions associated with the JAK2V617F mutation.
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Affiliation(s)
- Takuya Izumi-Tamura
- Division of Cancer RNA Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
- Division of Hematology, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
| | - Kosuke Takano
- Division of Hematology, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
- Division of Hematology, Jichi Medical University Saitama Medical Center, 1-847 Amanuma, Omiya-Ku, Saitama-Shi, Saitama, 330-8503, Japan
| | - Shigeki Nagao
- Division of Hematology, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
- Department of Palliative and Supportive Care, Yokohama Minami Kyosai Hospital, 1-21-1, Mutsuura-Higashi, Kanazawa, Yokohama, Kanagawa, 236-0037, Japan
| | - Noriaki Tachi
- Division of Hematology, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Sho Sato
- Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Masaya Nakagawa
- Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Takehiro Sone
- Division of Hematology, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Kohei Takada
- Division of Hematology, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Hiraku Ogata
- Division of Hematology, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Keita Saito
- Division of Hematology, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Shoichiro Kato
- Division of Hematology, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Takaaki Maekawa
- Division of Hematology, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
- Division of Palliative Care, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Akihide Yoshimi
- Division of Cancer RNA Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Shinichi Kobayashi
- Division of Hematology, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
| | - Fumihiko Kimura
- Division of Hematology, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
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