|
1
|
Subash R, Duan C, Shah A, Hines DM, Zhang M, Kongnakorn T, Dworatzek E, Kisser A, Hagan M. Decision model to evaluate the cost of clinical events associated with switching from apixaban to rivaroxaban among patients with non-valvular atrial fibrillation in the United States and Germany. J Med Econ 2025; 28:224-234. [PMID: 39819252 DOI: 10.1080/13696998.2025.2450933] [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: 10/30/2024] [Revised: 01/03/2025] [Accepted: 01/06/2025] [Indexed: 01/19/2025]
Abstract
AIMS Direct-acting oral anticoagulants (DOACs) have emerged as the preferred treatment for nonvalvular atrial fibrillation (NVAF). However, evidence concerning the economic outcomes of DOAC switching remains limited. This study aimed to assess the economic outcomes of DOAC switching in the US and Germany, two countries with a high AF prevalence and DOAC utilization. METHODS A decision model was developed to assess the incidence and cost of stroke/systemic embolism (SE) and major bleeding (MB) associated with switching from apixaban to rivaroxaban in patients with NVAF. The model compared two scenarios: continuers (patients continuing apixaban) and switchers (patients switching from apixaban to rivaroxaban). Model inputs on clinical event rates were sourced from a published real-world study, cost inputs were from a standard costing database and published literature. The analysis was conducted over a 1-year time horizon from US Medicare fee-for-service and German public healthcare payer perspectives. RESULTS Over one year, 47,036 patients among a hypothetical plan size of 1,000,000 US Medicare fee-for-service members and 1,019,079 patients among the German adult population size of 70,107,122 were estimated to be treated for NVAF with apixaban. Switching all patients from apixaban to rivaroxaban resulted in 1,498 and 32,447 additional clinical events (stroke/SE and MB) and deaths in the US and Germany, respectively, compared to continuing with apixaban. This led to a total incremental cost of $17.3 million and €153 million from Medicare fee-for-service and German public healthcare perspectives, respectively. LIMITATIONS The incidence and hazard ratios of clinical events informing this analysis were based on a US commercial and Medicare Advantage population and may not be generalizable to other populations. CONCLUSIONS Switching from apixaban to rivaroxaban was associated with increased clinical events, deaths, and higher medical care costs, potentially representing a less favorable strategy economically compared to continuing apixaban among patients with NVAF.
Collapse
Affiliation(s)
| | - Cecilia Duan
- Health Economics and Market Access, Evidera, London, UK
| | - Anshul Shah
- Health Economics and Market Access, Evidera, Mumbai, India
| | | | - Michelle Zhang
- Global HEOR, Bristol Myers Squibb Company, NJ, USA
- Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA
| | | | | | - Agnes Kisser
- Access and Value, Pfizer Pharma GmbH, Berlin, Germany
| | | |
Collapse
|
|
2
|
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.
Collapse
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
| |
Collapse
|
|
3
|
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.
Collapse
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
| | | |
Collapse
|
|
4
|
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.
Collapse
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.
| |
Collapse
|
|
5
|
Wu JY, Lai CC, Lin HJ, Lu KH, Hsu WH, Chu TY. Comparing the effectiveness and safety of direct oral anticoagulants and warfarin in patients with cerebral venous thrombosis: A real-world study. J Stroke Cerebrovasc Dis 2025; 34:108290. [PMID: 40090604 DOI: 10.1016/j.jstrokecerebrovasdis.2025.108290] [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: 10/23/2024] [Revised: 03/11/2025] [Accepted: 03/12/2025] [Indexed: 03/18/2025] Open
Abstract
BACKGROUND Cerebral venous thrombosis (CVT), a rare stroke variant, poses treatment challenges, especially in young individuals. While guidelines recommend heparin followed by warfarin, warfarin has limitations. Direct oral anticoagulants (DOACs) offer a potential alternative, but evidence on their use in CVT management is limited. The TriNetX study aimed to provide real-world insights into DOAC efficacy and safety for CVT. METHODS We conducted a retrospective cohort study utilizing data from TriNetX to identify patients with CVT. Propensity score matching (PSM) was used to balance the covariates between patients receiving DOACs and those receiving warfarin. The primary outcome was recurrent CVT, with secondary outcomes including intracerebral hemorrhage and all-cause mortality. RESULTS Among 1,507 patients with CVT, PSM generated 551 matched individuals in both the study and control groups. The study group that received DOACs exhibited a lower risk of CVT recurrence (Hazard Ratio [HR], 0.77; 95 % Confidence Interval [CI], 0.628-0.97) and a higher 360-day event-free survival rate (p < 0.001). Subgroup analyses revealed significantly reduced recurrent CVT risk in the study group, particularly among females (HR, 0.67; 95 % CI, 0.50-0.89), individuals aged 41-64 years (HR, 0.52; 95 % CI, 0.35-0.75), and patients with normal weight (HR, 0.65; 95 % CI, 0.50-0.84). Moreover, recipients of DOACs had a lower risk of intracerebral hemorrhage (HR, 0.62; 95 % CI, 0.43-0.91) and comparable all-cause mortality (HR, 1.03; 95 % CI, 0.67-1.59). CONCLUSIONS This study underscores the potential of DOACs as a promising treatment for CVT, demonstrating reduced recurrence and intracerebral hemorrhage risks with comparable all-cause mortality.
Collapse
Affiliation(s)
- Jheng-Yan Wu
- Department of Nutrition, Chi Mei Medical Center, Tainan, Taiwan; Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chih-Cheng Lai
- Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Huey-Juan Lin
- Department of Neurology, Chi Mei Medical Center, Tainan, Taiwan
| | - Kuan-Hsien Lu
- Department of Neurology, Chi Mei Medical Center, Tainan, Taiwan
| | - Wan-Hsuan Hsu
- Department of General Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Ting-Ying Chu
- Department of Neurology, Chi Mei Medical Center, Tainan, Taiwan.
| |
Collapse
|
|
6
|
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.
Collapse
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
| |
Collapse
|
|
7
|
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.
Collapse
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
| |
Collapse
|
|
8
|
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.
Collapse
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.
| |
Collapse
|
|
9
|
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.
Collapse
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
| |
Collapse
|
|
10
|
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.
Collapse
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.
| |
Collapse
|
|
11
|
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.
Collapse
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
| |
Collapse
|
|
12
|
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.
Collapse
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
| | | | | |
Collapse
|
|
13
|
Wang D, An Y, Zhou X, Chai H, Huo J, Li C, Du M, Dai D, Li C, Chen H. Relevance of selected pharmacogenetic polymorphisms to bleeding and thromboembolic risks in Chinese patients taking direct-acting oral anticoagulants. Br J Clin Pharmacol 2025. [PMID: 40400080 DOI: 10.1002/bcp.70078] [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: 02/25/2025] [Revised: 03/30/2025] [Accepted: 04/04/2025] [Indexed: 05/23/2025] Open
Abstract
AIMS Gene polymorphisms play a critical role in the variability of plasma concentrations of direct-acting oral anticoagulants (DOACs). In this study, we aimed to investigate the effects of genetic variants on the clinical outcomes of Chinese patients treated with DOACs. METHODS The retrospective study recruited 720 patients with nonvalvular atrial fibrillation who were receiving dabigatran, rivaroxaban or edoxaban. Cox regression models were employed to compare the clinical outcomes between carriers and noncarriers of the key single nucleotide polymorphisms. RESULTS Results revealed that the CES1 rs2244613 C allele significantly reduced bleeding events in patients treated with dabigatran (adjusted hazard ratio 0.33, 95% confidence interval 0.13-0.85, P = .021). The carriage of ABCB1 rs1045642 T allele was associated with a lower risk of thromboembolism in rivaroxaban users (adjusted hazard ratio 0.19, 95% confidence interval 0.07-0.57, P = .003). Additionally, a trend toward statistical significance (P = .052) was observed between the SLCO1B1 rs4149056 C allele and bleeding risk among the edoxaban users. CONCLUSIONS Our study showed that the CES1 rs2244613 and ABCB1 rs1045642 alleles were associated with outcome events in Chinese patients taking dabigatran and rivaroxaban, respectively. The findings could help predict clinical outcomes and develop personalized anticoagulation treatment strategies for Chinese patients taking DOACs.
Collapse
Affiliation(s)
- Dongxu Wang
- Cardiovascular Department, Beijing Hospital, National Center of Gerontology, Beijing, China
- Arrhythmia Center, Fuwai Hospital, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases, Beijing, China
| | - Yang An
- Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiaoyue Zhou
- Cardiovascular Department, Beijing Hospital, National Center of Gerontology, Beijing, China
| | - Huaru Chai
- Cardiovascular Department, Beijing Hospital, National Center of Gerontology, Beijing, China
| | - Jiani Huo
- Cardiovascular Department, Beijing Hospital, National Center of Gerontology, Beijing, China
| | - Chunrong Li
- Cardiovascular Department, Beijing Hospital, National Center of Gerontology, Beijing, China
| | - Minghui Du
- Cardiovascular Department, Beijing Hospital, National Center of Gerontology, Beijing, China
| | - Dapeng Dai
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China
| | - Chuanbao Li
- Department of Clinical Laboratory, Beijing Hospital, National Center of Gerontology, Beijing, China
| | - Hao Chen
- Cardiovascular Department, Beijing Hospital, National Center of Gerontology, Beijing, China
| |
Collapse
|
|
14
|
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.
Collapse
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
| |
Collapse
|
|
15
|
Providencia R, Ali H, Barra S, Creta A, Kukendra-Rajah K, Kanagaratnam P, Farkowski MM, Cappato R. Ablation of atrial fibrillation and risk of stroke: a Meta-analysis. Heart Rhythm 2025:S1547-5271(25)02445-2. [PMID: 40398548 DOI: 10.1016/j.hrthm.2025.05.021] [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: 02/03/2025] [Revised: 04/24/2025] [Accepted: 05/14/2025] [Indexed: 05/23/2025]
Abstract
BACKGROUND Despite treatment with anticoagulants, patients with atrial fibrillation (AF) remain exposed to a relevant residual risk of stroke. It remains to be proven if catheter ablation of AF can lead to an additional stroke protection benefit in these patients. OBJECTIVE Investigating a possible stroke protective benefit by catheter ablation in AF. METHODS Systematic review of contemporary randomized controlled trials comparing catheter ablation vs. medical treatment. We searched MEDLINE, EMBASE and CENTRAL in February 2025, pooled data through risk ratios (RRs) with 95% confidence intervals (CIs), and calculated the Number Needed to Treat (NNT). Quality of evidence was assessed using the GRADE framework. Sub-group and sensitivity analyses were performed for presence/absence of heart failure, CHA2DS2VASc≥2 or <2, paroxysmal/persistent AF, early ablation, studies allowing discontinuation of oral anticoagulation post-ablation, higher/lower quality, published ≤5 vs >5 years ago, and ≥12 vs < 12 months follow-up. RESULTS We identified 18 eligible randomized controlled trials, including 5877 patients. Catheter ablation was associated with a significant reduction in stroke (RR: 0.63, 95%CI 0.45 to 0.87, P=0.006; Quality of evidence: Moderate), with low heterogeneity observed (I2=0), and a NNT of 78.7 patients to prevent one stroke. Sub-group and sensitivity analyses yielded similar estimates with 30 to 40% relative risk reduction for all sub-analyses, except for trials with less than one year of follow-up. CONCLUSION Pooling of high-quality randomized controlled trial data suggests that catheter ablation may lead to significant stroke reduction. A confirmatory trial will be required to provide a conclusive answer to this matter.
Collapse
Affiliation(s)
- Rui Providencia
- Institute of Health Informatics Research, University College London, London, UK; Barts Heart Centre, St Bartholomew's Hospital, London, UK.
| | - Hussam Ali
- Arrhythmia and Clinical Electrophysiology Center, IRCCS, MultiMedica Group, Sesto San Giovanni, Milan, Italy
| | - Sérgio Barra
- Department of Cardiology, Hospital da Luz Arrábida, Vila Nova de Gaia, Portugal
| | - Antonio Creta
- Institute of Health Informatics Research, University College London, London, UK; Barts Heart Centre, St Bartholomew's Hospital, London, UK
| | - Kishore Kukendra-Rajah
- Institute of Health Informatics Research, University College London, London, UK; Barts Heart Centre, St Bartholomew's Hospital, London, UK
| | - Prapa Kanagaratnam
- Imperial College Healthcare NHS Trust, London, UK; Imperial College, London, UK
| | - Michal M Farkowski
- Department of Cardiology, Ministry of Interior and Administration National Medical Institute, Warsaw, Poland
| | - Riccardo Cappato
- Arrhythmia and Clinical Electrophysiology Center, IRCCS, MultiMedica Group, Sesto San Giovanni, Milan, Italy
| |
Collapse
|
|
16
|
Khan F, Mallick D, Wolman D, Torabi R, Moldovan K, Jayaraman M, Furie K, Yaghi S. Management of carotid artery web: a nationwide survey of vascular neurologists versus neurointerventionalists. J Neurointerv Surg 2025:jnis-2025-023232. [PMID: 40379476 DOI: 10.1136/jnis-2025-023232] [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: 02/08/2025] [Accepted: 04/10/2025] [Indexed: 05/19/2025]
Abstract
BACKGROUND Carotid artery web (CW) is an under-recognized cause of cryptogenic stroke, with variability in practice and controversy regarding its optimal management. Due to the lack of society guidelines, it is unclear how neurointerventional radiologists (NIRs) and vascular neurologists approach this condition. Therefore, we conducted a survey to understand practice patterns for the management of CW. METHODS A 10-question survey, including demographic data and clinical vignettes, was developed using REDCap (Research Electronic Data Capture) and sent to board-certified vascular neurologists and NIRs. Responses were categorized into binary outcomes (medical therapy vs carotid revascularization). Statistical analyses, including Chi-square, Fisher's exact, and Kruskal-Wallis, were used for group comparisons. RESULTS Of 1640 participants, 247 completed the survey, with 77% being vascular neurologists and 23% neurointerventionalists. Participants identified cryptogenic stroke (80.1%) and recurrent stroke (74.4%) as key factors considering CW as the underlying stroke etiology. For a cryptogenic ischemic stroke, neurointerventionalists were more likely than neurologists to favor carotid revascularization (52% vs 37%, p=0.035). In patients with ischemic stroke and competing mechanisms such as atrial fibrillation, nearly half of neurointerventionalists, but only one-third of neurologists, recommended revascularization for secondary prevention (48% vs 31%, p=0.021). NIRs, when compared with neurologists, had a strong preference for carotid artery stenting over carotid endarterectomy (86% vs 35%, p=0.002). CONCLUSIONS There is clinical equipoise regarding the management of CW and ischemic stroke. Randomized clinical trials are needed to minimize variability in treatment approaches.
Collapse
Affiliation(s)
- Farhan Khan
- Neurology, Brown University, Providence, Rhode Island, USA
| | - Dania Mallick
- Neurology, Brown University, Providence, Rhode Island, USA
| | - Dylan Wolman
- Radiology, Brown University, Providence, Rhode Island, USA
| | - Radmehr Torabi
- Neurosurgery, Brown University, Providence, Rhode Island, USA
| | | | | | - Karen Furie
- Neurology, Brown University, Providence, Rhode Island, USA
| | - Shadi Yaghi
- Neurology, Brown University, Providence, Rhode Island, USA
| |
Collapse
|
|
17
|
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
| |
Collapse
|
|
18
|
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.
Collapse
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.
| |
Collapse
|
|
19
|
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.
Collapse
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
| |
Collapse
|
|
20
|
AlTuraiki AM, AlMalag HM, AlShehri SM, AlKendi JM, AlAnazi AM, AlAbdulkarim DA, AlAujan SS. Pattern of anticoagulation prescription for elderly atrial fibrillation patients with or without severe dementia: A retrospective analysis of patient data. Medicine (Baltimore) 2025; 104:e42343. [PMID: 40355244 PMCID: PMC12074037 DOI: 10.1097/md.0000000000042343] [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] [Received: 10/22/2024] [Accepted: 04/17/2025] [Indexed: 05/14/2025] Open
Abstract
Atrial fibrillation (AF) is a very common type of cardiac arrhythmia. Use of an anticoagulant is highly recommended. We aimed to identify the pattern of prescribing of an oral anticoagulant (OA) in patients with AF and severe dementia or patients with AF aged > 80 years. A retrospective review of medical charts was conducted in 2 tertiary care centers in Riyadh, Saudi Arabia: King Saud University Medical City and King Abdulaziz Medical City. Data for people with AF retrieved between January 2016 and December 2020 from hospital information systems. Collected data included demographics, medical history, medication history (including use of an OA or antiplatelet agent), stroke and major bleeding history. Adjusted binary logistic regression was used to predict the odds ratio (OR) of the primary outcome and secondary outcomes. The data of 620 patients were assessed. Most (60%) were women. The average age of study cohort was 79 ± 6.1 years. Most patients (88.2%) were prescribed an OA. The most commonly prescribed OA was a direct inhibitor of factor Xa (DIFXa; 48%), followed by a coumarin derivative (36%), and direct inhibitor of thrombin (16%). Patients using a coumarin derivative carried higher OR of developing severe dementia (adjusted OR = 2.687, 95%CI = 1.795-4.021, P-value < .001). Most patients suffering from AF were prescribed an OA. A DIFXa inhibitor was the most prescribed OA. Use of a coumarin derivative carried a high prevalence of dementia among our study cohort.
Collapse
Affiliation(s)
- Abdulrahman M. AlTuraiki
- Department of Pharmaceutical Care, Ministry of the National Guard – Health Affairs, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Haya M. AlMalag
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Shahad M. AlShehri
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Jumanah M. AlKendi
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Alanoud M. AlAnazi
- Department of Pharmaceutical Care, Ministry of the National Guard – Health Affairs, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Dalal A. AlAbdulkarim
- Department of Pharmaceutical Care, Ministry of the National Guard – Health Affairs, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Shiekha S. AlAujan
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| |
Collapse
|
|
21
|
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.
Collapse
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
| |
Collapse
|
|
22
|
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.
Collapse
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
| |
Collapse
|
|
23
|
Ahmed SR, Zeinhom MG, Ebied AAMK, Kamel IFM, Almoataz MA, Daabis AMA, Akl AZO, Mahmoud ELA, Alkhalefeh AG, Ouf SG, Mosbah SAA, Sirag IMI, Abouelnaga M, Khalil MFE. A multi-center study on the predictors of different subtypes of hemorrhagic transformation of brain infarction after thrombolysis in atrial fibrillation patients presented with embolic stroke. Sci Rep 2025; 15:15655. [PMID: 40325067 PMCID: PMC12053602 DOI: 10.1038/s41598-025-97968-3] [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: 12/23/2024] [Accepted: 04/08/2025] [Indexed: 05/07/2025] Open
Abstract
Embolic stroke is connected to a higher risk of hemorrhagic transformation (HT), functional disability, and mortality. Although, AF and HT are not one entity; no such study evaluated the factors, including AF types and treatment, which could predict the different types of HT in AF patients presenting with embolic stroke and administered alteplase. We aimed to assess the predictors of HT in general and predictors of different ECASS-based subtypes of post-alteplase HT in AF patients who experienced first-ever embolic ischemic stroke. Our study included 716 AF patients who presented with acute embolic stroke and received the full recommended dose of alteplase. The study comprised six parallel groups. The first group consisted of 509 patients who did not experience haemorrhagic transformation. The second group comprised 207 patients who had any HT. The third group comprised 87 patients with haemorrhagic infarction (HI)1. The fourth group comprised 62 patients with HI2. The fifth group comprised 33 patients with parenchymal hematoma (PH) 1, and the sixth group comprised 25 patients with PH 2. We evaluated the ability of different baseline characters and risk factors to predict the occurrence of HT in general and the predictors of occurrence of different ECASS-based HT subtypes. HT was detected in 207 patients (28.9%), older age, higher NIHSS, sustained AF, warfarin use, and higher HAS-BLED score were independent predictors of all ECASS-based subtypes of hemorrhagic transformation; moreover, anterior-circulation stroke was an independent predictor of PH 1 and PH 2. In atrial fibrillation patients presented with first-ever embolic stroke and received alteplase in Egypt and the United Arab Emirates, older age, higher NIHSS, sustained AF, warfarin use, and higher HAS-BLED score were independent predictors of all ECASS-based subtypes of haemorrhagic infarction; in addition, anterior-circulation stroke was an independent predictor of PH 1 and PH 2.Trial registration (clinicaltrials.gov NCT06653946), retrospectively registered on 23/10/2024.
Collapse
Affiliation(s)
- Sherihan Rezk Ahmed
- Neurology Department, Faculty of Medicine, Kafr El-Sheikh University, Elgeish Street, Kafr El-Sheikh, Egypt
| | - Mohamed G Zeinhom
- Neurology Department, Faculty of Medicine, Kafr El-Sheikh University, Elgeish Street, Kafr El-Sheikh, Egypt.
| | | | | | | | | | - Ahmed Zaki Omar Akl
- Neurology Department, Faculty of Medicine, Ain Shams University, Al Khalifa Elmamon St., Cairo, Egypt
| | | | | | - Shady G Ouf
- Cardiology Department, Phoenix Hospital, Abu Dhabi, United Arab Emirates
| | | | | | - Mohamed Abouelnaga
- Neurology Department, Faculty of Medicine, Alexandria University, Elgomhorea St., Alexandria, Egypt
| | | |
Collapse
|
|
24
|
Loggini A, Saleh Velez FG, Towner JE, Hornik J, Wallery Md SS, Battaglini D, Schwertman A, Nomani S, Hornik A, Qureshi AI, Del Brutto VJ. Two decades of trends in nontraumatic intracerebral hemorrhage care: A nationwide analysis. J Clin Neurosci 2025; 137:111300. [PMID: 40327920 DOI: 10.1016/j.jocn.2025.111300] [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: 03/10/2025] [Revised: 04/29/2025] [Accepted: 04/29/2025] [Indexed: 05/08/2025]
Abstract
PURPOSE This study aims to analyze the temporal trends of comorbidities, complications, and in-hospital mortality of non-traumatic intracerebral hemorrhages (ICH) over the past two decades using a nationwide inpatient sample. METHODS The National Inpatient Sample database was screened to identify patients hospitalized with ICH from 2002 to 2022. Socio-demographic characteristics, comorbidities, complications (including ischemic stroke, seizures, aspiration pneumonia, and deep vein thrombosis/pulmonary embolism DVT/PE), neurosurgical procedures, tracheostomy, and percutaneous gastrostomy placement were reviewed. Length of hospital stay and in-hospital mortality were analyzed. Temporal trends were determined using linear logistic regression models for each predetermined variable. For dichotomous variables, the natural logarithm was calculated to achieve a harmonic linear trend. Pairwise comparison was used for subgroup analyses. RESULTS A total of 467,117 patients with ICH were included in the study. From 2002 to 2022, there was a significant increase in comorbidities, including hypertension, diabetes, chronic kidney disease, obesity, and anticoagulant use, p < 0.01 for all. Patients' age progressively decreased over time (β:-0.104, 95 %CI: -0.124-0.085, p < 0.01). Notably, a temporal increase in ischemic stroke (β:0.081, 95 %CI: 0.069-0.092, p < 0.01) and seizures (β:0.012, 95 %CI: 0.001-0.008, p < 0.01) was noted. Clot removal/decompression declined over the years (β:-0.039, 95 %CI: -0.057-0.022, p < 0.01) while EVD/VPS placement increased (β:, 95 %CI: -0.057-0.022, p < 0.01). Length of hospital stay increased yearly by 0.07 days (95 %CI: 0.04-0.08, p < 0.01). The average annual mortality rate significantly decreased by 2.43 % per year (95 %CI: -2.21 %-2.65 %, p < 0.01). In-hospital mortality rates declined more rapidly in urban areas compared to rural areas (0.99 % difference, 95 %CI: 0.5 %-1.48 %, p < 0.01). No statistical difference was observed among sex, racial or income groups; however, there was a trend toward a slower decline in in-hospital mortality among lower-income compared to higher-income groups. CONCLUSION Despite increasing patient complexity, in-hospital mortality has steadily decreased in ICH patients over the last two decades. These improvements have come at the cost of longer hospital stays. Profound inequities remain in the mortality rate in rural areas.
Collapse
Affiliation(s)
- Andrea Loggini
- Brain and Spine Institute. Southern Illinois Healthcare, Carbondale, IL, USA; Southern Illinois University School of Medicine, Carbondale, IL, USA.
| | - Faddi G Saleh Velez
- Brain Stimulation and Neurorehabilitation Laboratory, Department of Neurology. University of Oklahoma Health Sciences Center, Oklahoma City. OK, USA
| | - James E Towner
- Brain and Spine Institute. Southern Illinois Healthcare, Carbondale, IL, USA; Department of Neurosurgery, John Stroger Hospital of Cook County, Chicago, IL, USA
| | - Jonatan Hornik
- Brain and Spine Institute. Southern Illinois Healthcare, Carbondale, IL, USA; Southern Illinois University School of Medicine, Carbondale, IL, USA
| | - Shawn S Wallery Md
- Brain and Spine Institute. Southern Illinois Healthcare, Carbondale, IL, USA; Department of Neurology University of Illinois, Rockford, IL, USA
| | - Denise Battaglini
- Anesthesia and Intensive Care, IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Italy
| | - Amber Schwertman
- Southern Illinois University School of Medicine, Carbondale, IL, USA
| | - Sarmad Nomani
- Brain and Spine Institute. Southern Illinois Healthcare, Carbondale, IL, USA
| | - Alejandro Hornik
- Brain and Spine Institute. Southern Illinois Healthcare, Carbondale, IL, USA; Southern Illinois University School of Medicine, Carbondale, IL, USA
| | - Adnan I Qureshi
- Zeenat Qureshi Stroke Institutes and Department of Neurology, University of Missouri, Columbia, MO, USA
| | - Victor J Del Brutto
- Department of Neurology, University of Miami, Miller School of Medicine, Miami, FL, USA
| |
Collapse
|
|
25
|
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.
Collapse
|
|
26
|
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.
Collapse
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
| |
Collapse
|
|
27
|
Attelind S, Eriksson N, Wadelius M, Hallberg P. Genome-wide association study of direct oral anticoagulants and their relation to bleeding. Eur J Clin Pharmacol 2025; 81:771-783. [PMID: 40116934 PMCID: PMC12003525 DOI: 10.1007/s00228-025-03821-x] [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: 11/29/2024] [Accepted: 03/03/2025] [Indexed: 03/23/2025]
Abstract
PURPOSE Direct oral anticoagulants (DOACs) are used to prevent and treat thromboembolic events in adults. We aimed to investigate whether pharmacogenomic variation contributes to the risk of bleeding during DOAC treatment. METHODS Cases were recruited from reports of bleeding sent to the Swedish Medical Products Agency (n = 129, 60% men, 93% Swedish, 89% on factor Xa inhibitors) and compared with population controls (n = 4891) and a subset matched for exposure to DOACs (n = 353). We performed a genome-wide association study, with analyses of candidate single nucleotide polymorphisms (SNPs) and candidate gene set analyses. RESULTS Forty-four cases had major, 37 minor, and 48 clinically relevant non-major (CRNM) bleeding. When cases were compared with matched controls, BAIAP2L2 rs142001534 was significantly associated with any bleeding and major/CRNM bleeding (P = 4.66 × 10-8 and P = 3.28 × 10-8, respectively). The candidate SNP CYP3A5 rs776746 was significantly associated with major and major/CRNM bleeding (P = 0.00020 and P = 0.00025, respectively), and ABCG2 rs2231142 was nominally associated with any bleeding (P = 0.01499). Rare coding variants in the candidate gene VWF were significantly associated with any bleeding (P = 0.00296). CONCLUSION BAIAP2L2, CYP3A5, ABCG2, and VWF may be associated with bleeding in DOAC-treated patients. The risk estimates of the candidate variants in CYP3A5 and ABCG2 were in the same direction as in previous studies. The Von Willebrand Factor gene (VWF) is linked to hereditary bleeding disorders, while there is no previous evidence of bleeding associated with BAIAP2L2.
Collapse
Affiliation(s)
- Sofia Attelind
- Department of Medical Sciences, Clinical Pharmacogenomics, Uppsala University, Uppsala, Sweden.
- Department of Drug Safety, Swedish Medical Products Agency, Uppsala, Sweden.
| | - Niclas Eriksson
- Department of Medical Sciences, Clinical Pharmacogenomics, Uppsala University, Uppsala, Sweden
- Uppsala Clinical Research Center, Uppsala University Hospital, Uppsala, Sweden
| | - Mia Wadelius
- Department of Medical Sciences, Clinical Pharmacogenomics, Uppsala University, Uppsala, Sweden
| | - Pär Hallberg
- Department of Medical Sciences, Clinical Pharmacogenomics, Uppsala University, Uppsala, Sweden
| |
Collapse
|
|
28
|
Harel Z, Smyth B, Badve SV, Blum D, Beaubien-Souligny W, Silver SA, Clark E, Suri R, Mavrakanas TA, Sasal J, Prasad B, Eikelboom J, Tennankore K, Rigatto C, Prce I, Madore F, Mac-Way F, Steele A, Zeng Y, Sholzberg M, Dorian P, Yan AT, Sood MM, Gladstone DJ, Tseng E, Kitchlu A, Walsh M, Sapir D, Oliver MJ, Krishnan M, Kiaii M, Wong N, Kotwal S, Battistella M, Acedillo R, Lok C, Weir M, Wald R. Anticoagulation for Patients with Atrial Fibrillation Receiving Dialysis: A Pilot Randomized Controlled Trial. J Am Soc Nephrol 2025; 36:901-910. [PMID: 39495569 PMCID: PMC12059112 DOI: 10.1681/asn.0000000000000495] [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: 06/07/2024] [Accepted: 10/29/2024] [Indexed: 11/06/2024] Open
Abstract
Key Points Is performing a large definitive trial to establish the optimal anticoagulation strategy in dialysis recipients with atrial fibrillation feasible? One hundred fifty-one patients at 28 dialysis centers were enrolled and randomized to apixaban (n =51), warfarin (n =52), or no oral anticoagulation (n =48). Despite coronavirus disease–related pauses, recruitment was completed in 30 months, with 83% of participants completing follow-up in their assigned treatment arm. Background Atrial fibrillation is common in individuals receiving dialysis. The role of oral anticoagulation in this population is uncertain given its exclusion from previous seminal clinical trials. Our objective was to determine the feasibility of performing a large definitive trial to establish the optimal anticoagulation strategy in individuals with atrial fibrillation receiving dialysis. Methods The Strategies for the Management of Atrial Fibrillation in Patients Receiving Dialysis trial was a parallel-group, open-label, allocation-concealed, pilot randomized control trial that took place at 28 centers in Canada and Australia. The trial included adults (18 years or older) undergoing dialysis with a history of nonvalvular atrial fibrillation who met the CHADS-65 criteria. Participants were randomized 1:1:1 to receive dose-adjusted warfarin, apixaban 5 mg twice daily, or no oral anticoagulation and followed for 26 weeks. The primary outcomes evaluated the following measures of feasibility: (1 ) recruitment of the target population within 2 years from the start of the trial and (2 ) adherence of >80% of randomized patients to the allocated treatment strategy at the conclusion of follow-up. Secondary outcomes included stroke and bleeding. Results From December 2019 to June 2022, 151 patients were enrolled and randomized to apixaban (n =51), warfarin (n =52), or no oral anticoagulation (n =48). Allowing for pauses related to the coronavirus disease pandemic, recruitment was completed in 30 months, and 123 (83%) of participants completed follow-up in their allocated treatment arm. There was one adjudicated stroke event. Eight participants had a major bleeding event (four warfarin, two apixaban, two no oral anticoagulation). Death occurred in 15 participants (nine warfarin, two apixaban, four no oral anticoagulation). Time in the therapeutic range for warfarin recipients was 58% (interquartile range, 47%–70%). Conclusions We have demonstrated the feasibility of recruitment and adherence in a trial that compared different anticoagulation strategies in patients with atrial fibrillation receiving dialysis. Clinical Trial registry name and registration number: Strategies for the Management of Atrial Fibrillation in Patients Receiving Dialysis (SAFE-D), NCT03987711 . Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2025_04_09_ASN0000000000000495.mp3
Collapse
Affiliation(s)
- Ziv Harel
- Division of Nephrology, Department of Medicine, St. Michael's Hospital, Toronto, Ontario, Canada
| | - Brendan Smyth
- Department of Nephrology, St. George Hospital, Kogarah, New South Wales, Australia
| | - Sunil V. Badve
- Department of Nephrology, St. George Hospital, Kogarah, New South Wales, Australia
| | - Daniel Blum
- Division of Nephrology, McGill University, Montreal, Quebec, Canada
| | | | - Samuel A. Silver
- Division of Nephrology, Queen's University, Kingston, Ontario, Canada
| | - Edward Clark
- Division of Nephrology, Department of Medicine, The Ottawa Hospital, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Rita Suri
- Division of Nephrology, McGill University, Montreal, Quebec, Canada
| | | | - Joanna Sasal
- Division of Nephrology, St. Joseph's Hospital, Toronto, Ontario, Canada
| | - Bhanu Prasad
- Division of Nephrology, University of Saskatchewan, Regina, Saskatchewan, Canada
| | - John Eikelboom
- Division of Hematology, McMaster University, Hamilton, Ontario, Canada
| | - Karthik Tennankore
- Division of Nephrology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Claudio Rigatto
- Division of Nephrology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Ivana Prce
- Division of Nephrology, St. Michael's Hospital, Toronto, Ontario, Canada
| | - Francois Madore
- Department of Medecine, Université de Montréal, Montréal, Quebec, Canada
| | - Fabrice Mac-Way
- Division of Nephrology, Laval University, Laval, Quebec, Canada
| | - Andrew Steele
- Division of Nephrology, Lakeridge Hospital, Oshawa, Ontario, Canada
| | - Yangmin Zeng
- Division of Nephrology, University of British Columbia, Surrey, British Columbia, Canada
| | - Michelle Sholzberg
- Division of Hematology/Oncology, Departments of Medicine and, Laboratory Medicine and Pathobiology, St. Michael's Hospital, Li Ka Shing Knowledge Institute, University of Toronto, Toronto, Ontario, Canada
| | - Paul Dorian
- Division of Cardiology, Department of Medicine, St. Michael's Hospital Health, University of Toronto, Toronto, Ontario, Canada
| | - Andrew T. Yan
- Division of Cardiology, Department of Medicine, St. Michael's Hospital Health, University of Toronto, Toronto, Ontario, Canada
| | - Manish M. Sood
- Division of Nephrology, Department of Medicine, The Ottawa Hospital, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - David J. Gladstone
- Division of Neurology, Department of Medicine, Sunnybrook Research Institute, Hurvitz Brain Sciences Program, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
| | - Eric Tseng
- Division of Hematology/Oncology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Abhijat Kitchlu
- Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Michael Walsh
- Division of Nephrology, McMaster University, Hamilton, Ontario, Canada
| | - Danny Sapir
- Division of Nephrology, Oakville Trafalgar Hospital, Oakville, Ontario, Canada
| | - Matthew J. Oliver
- Division of Nephrology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Murali Krishnan
- Division of Nephrology, Royal Victoria Regional Health Centre, Barrie, Ontario, Canada
| | - Mercedeh Kiaii
- Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada
| | - Nikki Wong
- Division of Nephrology, Nepean Hospital, Sydney, New South Wales, Australia
| | - Sradha Kotwal
- Department of Nephrology, Prince of Wales Hospital, Australia The George Institute for Global Health, UNSW, Sydney, New South Wales, Australia
| | - Marisa Battistella
- Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Rey Acedillo
- Division of Nephrology, Thunder Bay Health Sciences Centre, Thunder Bay, Ontario, Canada
| | - Charmaine Lok
- Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Matthew Weir
- Division of Nephrology, Western University, London, Ontario, Canada
| | - Ron Wald
- Division of Nephrology, Department of Medicine, St. Michael's Hospital, Toronto, Ontario, Canada
| |
Collapse
|
|
29
|
Rogovoy NM, Kearing S, Zhou W, Freeman JV, Piccini JP, Al-Khatib SM, Zeitler EP. Incidence, Prevalence, and Trends in Mortality and Stroke Among Medicare Beneficiaries With Atrial Fibrillation: 2013 to 2019. Circ Cardiovasc Qual Outcomes 2025; 18:e011365. [PMID: 40184151 DOI: 10.1161/circoutcomes.124.011365] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 01/31/2025] [Indexed: 04/05/2025]
Abstract
BACKGROUND Atrial fibrillation (AF) is known to be associated with increased risks of stroke and death, but contemporary studies of this association are lacking. We evaluated trends in stroke and death among Medicare beneficiaries with AF between 2013 and 2019. METHODS Medicare fee-for-service beneficiaries >65 years old (2011-2019) were included. AF incidence and prevalence were calculated overall and by age group, sex, race, and rurality. Within incident cohorts, the 1-year stroke rate was assessed. Age- and sex-adjusted mortality at 30 days, 1 year, and 3 years was calculated in each incident cohort. RESULTS The mean number of Medicare beneficiaries with incident AF per year was 572 630 from 2013 to 2019 (30.44 per 1000 patient-years). The study cohort on average was 79±7.7 years old, 52% female, 88% white, and 83% urban dwelling. Incidence and prevalence of AF increased with age and was highest among White beneficiaries; the incidence was greater in male compared with female beneficiaries. Differences by rurality were not seen. Overall AF prevalence per 1000 beneficiaries increased minimally but steadily from 2013 to 2019 reflecting an increase among male (104-109 per 1000) but not female beneficiaries (82.5 per 1000). The 1-year rate of stroke after incident AF peaked in the 2015 cohort (50.5 per 1000); the rate was at its lowest among the 2018 cohort (41.89 per 1000). Incident AF was associated with mortality that was 3.2× greater than expected at 1 year, but overall mortality and the magnitude of the AF-related mortality risk decreased steadily over time from 22% to 20%. CONCLUSIONS From 2013 to 2019, AF incidence and prevalence among Medicare beneficiaries were relatively stable but have varied by important demographic subgroups with age and sex remaining powerful risk factors. In contrast, mortality and stroke after incident AF have decreased significantly throughout this era.
Collapse
Affiliation(s)
- Nichole M Rogovoy
- Department of Medicine & Heart and Vascular Center, Division of Cardiovascular Medicine, Dartmouth-Hitchcock Medical Center, Dartmouth Health, Lebanon NH (N.M.R., S.K., W.Z., E.P.Z.)
| | - Stephen Kearing
- Department of Medicine & Heart and Vascular Center, Division of Cardiovascular Medicine, Dartmouth-Hitchcock Medical Center, Dartmouth Health, Lebanon NH (N.M.R., S.K., W.Z., E.P.Z.)
| | - Weiping Zhou
- Department of Medicine & Heart and Vascular Center, Division of Cardiovascular Medicine, Dartmouth-Hitchcock Medical Center, Dartmouth Health, Lebanon NH (N.M.R., S.K., W.Z., E.P.Z.)
| | - James V Freeman
- Department of Medicine, Yale School of Medicine, New Haven, CT (J.V.F.)
| | - Jonathan P Piccini
- Department of Medicine, Duke University Medical Center and Duke Clinical Research Institute, Durham, NC (J.P.P., S.M.A.-K.)
| | - Sana M Al-Khatib
- Department of Medicine, Duke University Medical Center and Duke Clinical Research Institute, Durham, NC (J.P.P., S.M.A.-K.)
| | - Emily P Zeitler
- Department of Medicine & Heart and Vascular Center, Division of Cardiovascular Medicine, Dartmouth-Hitchcock Medical Center, Dartmouth Health, Lebanon NH (N.M.R., S.K., W.Z., E.P.Z.)
- The Dartmouth Institute, Lebanon, NH; and Geisel School of Medicine at Dartmouth, Hanover, NH (E.P.Z.)
| |
Collapse
|
|
30
|
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.
Collapse
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
| |
Collapse
|
|
31
|
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.
Collapse
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
| | | | | |
Collapse
|
|
32
|
Dobesh PP, Volkl AA, Pap ÁF, Damaraju CV, Levitan B, Yuan Z, Amin AN. Benefit-Risk Assessment of Rivaroxaban in Older Patients With Nonvalvular Atrial Fibrillation or Venous Thromboembolism. Drugs Aging 2025; 42:469-484. [PMID: 40163217 PMCID: PMC12053352 DOI: 10.1007/s40266-025-01192-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/17/2025] [Indexed: 04/02/2025]
Abstract
BACKGROUND Both bleeding and adverse ischemic events increase with age, compounding the benefit-risk balance of anticoagulants in older patients. We present analyses using benefit-risk methods to better understand the age-dependence of the benefit-risk profile of rivaroxaban in patients with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). METHODS Randomized controlled trial data from the ROCKET-AF (NVAF) and EINSTEIN DVT, EINSTEIN PE, EINSTEIN-Extension, and EINSTEIN CHOICE in (VTE) were used. For ROCKET-AF, benefits and risks were assessed with incidence rates for key thrombotic and bleeding endpoints and a net clinical benefit (NCB) measure. Cumulative incidences (estimated by the Kaplan-Meier method) were estimated at day 185 for EINSTEIN and EINSTEIN Extension and 1 year for EINSTEIN CHOICE. Incidence differences were calculated for the overall population and age subgroups of < 65, 65-75, and > 75 years. RESULTS In ROCKET-AF, rate differences in the composite NCB outcome (vascular death, stroke, myocardial infarction, fatal bleeding, critical organ bleeding, and non-CNS systemic embolism) favored rivaroxaban overall and by age < 65, 65-75, and > 75 years (-84, -25, -61, and -150 cases per 10,000 patient-years, respectively). In the pooled EINSTEIN DVT and EINSTEIN PE studies, cumulative incidence differences for the composite NCB outcome (recurrent VTE and major bleeding) were -103, 3, -105, and -544 per 10,000 patients, respectively. For extended VTE treatment with rivaroxaban versus placebo in EINSTEIN-Extension, NCB results were -536, -492, -556, and -601 per 10,000 patients, respectively. In the EINSTEIN CHOICE analysis, NCB favored rivaroxaban 20 mg versus aspirin (-284, -255, -339, and -338, respectively) and rivaroxaban 10 mg versus aspirin (-339, -328, -485, and -80, respectively). CONCLUSIONS This analysis demonstrated a positive benefit-risk profile with rivaroxaban versus trial comparators in older patients with NVAF or VTE, with benefit-risk increasingly favoring rivaroxaban with increasing age. CLINICAL TRIAL REGISTRATION http://ClinicalTrials.gov , identifiers: NCT00403767 (ROCKET-AF), NCT00440193 (EINSTEIN DVT), NCT00439777 (EINSTEIN PE), NCT00439725 (EINSTEIN Extension), and NCT02064439 (EINSTEIN CHOICE).
Collapse
Affiliation(s)
- Paul P Dobesh
- University of Nebraska Medical Center College of Pharmacy, 986120 Nebraska Medical Center, Omaha, NE, 68198-6120, USA.
| | | | | | | | | | | | - Alpesh N Amin
- Irvine Department of Medicine, Division of Hospital Medicine and Palliative Medicine, School of Medicine, University of California, Irvine, CA, USA
| |
Collapse
|
|
33
|
Zolio L, Cohen H, Isenberg D. Challenges of anticoagulation in patients with systemic lupus erythematosus. Expert Opin Pharmacother 2025; 26:849-862. [PMID: 40253682 DOI: 10.1080/14656566.2025.2491509] [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: 12/30/2024] [Revised: 04/06/2025] [Accepted: 04/07/2025] [Indexed: 04/22/2025]
Abstract
INTRODUCTION Anticoagulation is frequently required for patients with systemic lupus erythematosus (SLE), given their high prevalence of cardiovascular disease and thrombosis, due to the complexity of disease pathophysiology, some overlap with antiphospholipid syndrome (APS), comorbidities, prevalent cardiovascular risk factors and treatment complications. AREAS COVERED This article outlines the epidemiology and pathophysiology of cardiovascular disease and arterial and/or venous thrombosis in SLE, with/without APS. We discuss common cardiovascular comorbidities and thrombotic disorders that may present as a complication of SLE and/or APS and highlight recommendations in current guidelines for anticoagulation management, alongside relevant disease-specific considerations. We specifically comment on the use of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) in these patients. EXPERT OPINION Assessment of cardiovascular risk and aPL profile is paramount in SLE patients. While warfarin is preferred in high-risk APS patients, DOACs can be used in a selected group of SLE and/or APS patients with VTE and no prior history of arterial thrombosis. Initiating anticoagulation in the setting of Catastrophic APS (CAPS) can be extremely challenging. Knowledge gaps remain regarding the management of patients with recurrent arterial and/or venous thrombosis despite anticoagulation. Research is needed to optimize strategies to reduce thrombotic events in APS patients.
Collapse
Affiliation(s)
- Luigi Zolio
- Department of Ageing, Rheumatology and Regenerative Medicine, Division of Medicine, University College London, London, UK
- Department of Medicine, University of Melbourne at St Vincent's Hospital, Fitzroy, Australia
| | - Hannah Cohen
- Department of Haematology, University College London Hospitals NHS Foundation Trust and University College London, London, UK
| | - David Isenberg
- Department of Ageing, Rheumatology and Regenerative Medicine, Division of Medicine, University College London, London, UK
| |
Collapse
|
|
34
|
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.
Collapse
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
| | | |
Collapse
|
|
35
|
Eshmatov OR, Batalov RE, Khlynin MS, Archakov EA. Results of the Registry of Patients With Atrial Tachyarhythmias After Interventional Treatment (RPATIT). KARDIOLOGIIA 2025; 65:37-41. [PMID: 40331649 DOI: 10.18087/cardio.2025.4.n2803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 01/24/2025] [Indexed: 05/08/2025]
Abstract
Aim To study the long-term clinical profile of safety and efficacy of anticoagulant therapy (ACT) in patients with atrial tachyarrhythmias (AT) after interventional treatment.Material and methods A total of 5,611 medical records of patients managed in the Department of Surgical Treatment of Complex Heart Rhythm Disorders and Electrical Pacing of the Cardiology Research Institute of Tomsk National Research Medical Center (TNRMC) from 01.01.2017 through 31.12.2019 was analyzed. The study included 1,342 of the patients with various forms of AT who underwent the catheter treatment for heart rhythm disorders.Results The administration of ACT to patients with AT after the interventional treatment is safe, since the combined use of an invasive strategy and ACT does not increase the risk of major and minor bleeding. The effective intervention allows significantly reducing the risk of ischemic stroke in patients with paroxysmal and persistent atrial fibrillation and virtually completely excluding the likelihood of other thromboembolic complications.Conclusion Successful radiofrequency ablation/cryoballoon ablation of atrial fibrillation foci significantly reduces the risk of ischemic stroke, while the invasive strategy does not increase the risk of major and minor bleeding.
Collapse
Affiliation(s)
- O R Eshmatov
- Cardiology Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk
| | - R E Batalov
- Cardiology Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk
| | - M S Khlynin
- Cardiology Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk
| | - E A Archakov
- Cardiology Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk
| |
Collapse
|
|
36
|
Wang F, Li Z, Huang Y, Liu Q, Zhao L, Wang H, Gao H, Chen M, Lin Y, Li X, Chen M. Effect of ABCB1 SNP polymorphisms on the plasma concentrations and clinical outcomes of rivaroxaban in Chinese NVAF patients: a population pharmacokinetic-based study. Front Pharmacol 2025; 16:1574949. [PMID: 40365305 PMCID: PMC12069994 DOI: 10.3389/fphar.2025.1574949] [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: 02/11/2025] [Accepted: 04/08/2025] [Indexed: 05/15/2025] Open
Abstract
Background This study utilized a population pharmacokinetic (PPK) approach to assess the influence of ABCB1 genetic polymorphisms on the plasma concentrations and clinical outcomes of rivaroxaban. Methods The PPK model for rivaroxaban was developed using the nonlinear mixed-effects modelling approach and Monte Carlo simulations were employed to derive peak concentration (Cmax) and trough concentration (Ctrough). ABCB1 genetic variants were analyzed for their impact on the plasma concentrations and clinical outcomes. Results Analysis of 287 rivaroxaban plasma concentrations from 228 non-valvular atrial fibrillation (NVAF) patients revealed significant associations between AST (aspartate aminotransferase)/ALT (alanine aminotransferase) ratios and the apparent clearance (CL/F), the apparent volume of distribution (V/F). ABCB1 1236C>T TT and ABCB1 c.2482-2236C>T CC genotypes exhibited higher dose-adjusted Cmax (Cmax/D) compared to other relevant genotypes. Additionally, the ABCB1 3435C>T TT genotype showed lower dose-adjusted Ctrough (Ctrough/D) compared to CC or CT genotypes. For clinical outcomes, the ABCB1 c.2482-2236C>T CC genotype had a higher bleeding risk compared to TT (RR = 1.99, 95% CI 1.08-3.69) or CT genotypes (RR = 1.42, 95% CI 1.04-1.92), and ABCB1 3435C>T TT genotype showed a higher thromboembolic risk compared to CC genotype (RR = 3.48, 95% CI 1.02-11.85). Conclusion The PPK model incorporated CL/F and V/F with the covariate AST/ALT. Model-based simulations revealed that ABCB1 1236C>T, ABCB1 c.2482-2236C>T, and ABCB1 3435C>T genotypes had significant impacts on the plasma concentrations of rivaroxaban. Specifically, ABCB1 c.2482-2236C>T and ABCB1 3435C>T genotypes were associated with bleeding events and thromboembolic events, respectively.
Collapse
Affiliation(s)
- Fei Wang
- Department of Pharmacy, Fujian Provincial Geriatric Hospital, Clinical College of Fujian Medical University, Fuzhou, China
| | - Ze Li
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Youqi Huang
- Shengli Clinical College of Fujian Medical University, School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Qin Liu
- Department of Pharmacy, Fujian Provincial Geriatric Hospital, Clinical College of Fujian Medical University, Fuzhou, China
| | - Libin Zhao
- Department of Intensive Care Unit, Fujian Provincial Geriatric Hospital, Clinical College of Fujian Medical University, Fuzhou, China
| | - Honghong Wang
- Department of Pharmacy, Liuzhou Maternity and Child Healthcare Hospital, Affiliated Maternity Hospital, Liuzhou, China
- Department of Pharmacy, Liuzhou Hospital of Guangzhou Women and Children’s Medical Center, Liuzhou, China
| | - Hongjin Gao
- Shengli Clinical College of Fujian Medical University, Department of Pharmacy, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China
| | - Mingyu Chen
- Shengli Clinical College of Fujian Medical University, School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Yuze Lin
- Shengli Clinical College of Fujian Medical University, School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Xingang Li
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Min Chen
- Shengli Clinical College of Fujian Medical University, Department of Pharmacy, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China
| |
Collapse
|
|
37
|
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.
Collapse
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
| |
Collapse
|
|
38
|
Sohail MU, Ibrahim ZS, Waqas SA, Saad M, Hassan IN, Hameed I, Sohail MO, Ahmed R, Kumar V, Mohan A, Alraies C. A silent surge: Increasing stroke deaths among older adults with atrial fibrillation in the United States (1999-2020). J Stroke Cerebrovasc Dis 2025; 34:108328. [PMID: 40306391 DOI: 10.1016/j.jstrokecerebrovasdis.2025.108328] [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: 11/11/2024] [Revised: 02/20/2025] [Accepted: 04/21/2025] [Indexed: 05/02/2025] Open
Abstract
BACKGROUND Atrial fibrillation (AF) significantly increases stroke risk, particularly among older adults, leading to severe outcomes and elevated mortality. This study investigates trends and disparities in AF-related stroke mortality among U.S. adults aged 65 and older from 1999 to 2020. METHODS Mortality data from the CDC WONDER database were analyzed, identifying stroke as the underlying cause of death (ICD-10 codes I60-I69) with AF as a contributing cause (ICD-10 code I48). Age-adjusted mortality rates (AAMRs) per 100,000 persons were calculated. Annual percentage change (APC) and average annual percentage change (AAPC) were used to assess trends over time using Joinpoint regression. RESULTS A total of 197,453 deaths were recorded between 1999 and 2020. The AAMR increased from 20.85 in 1999 to 24.09 in 2020, reflecting an AAPC of 0.55 % (95 % CI: 0.19-0.95). Women had a slightly higher overall AAMR (21.69) compared to men (20.38). AAMR for Non-Hispanic (NH) Whites (22.15) was 1.5 times higher than that for Hispanics (14.17). Nonmetropolitan areas reported a higher AAMR (22.68) compared to metropolitan areas (21.03). The West had the highest regional overall AAMR (26.57). States in the top 90th percentile reported nearly double the rates of the lowest 10th percentile states. CONCLUSION AF-related stroke mortality in older adults has risen over the past two decades, with disparities across gender, race, and geography. Targeted interventions are essential to address these disparities and reduce the burden of AF-related stroke mortality.
Collapse
Affiliation(s)
| | | | - Saad Ahmed Waqas
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Muhammad Saad
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | | | | | | | - Raheel Ahmed
- National Heart and Lung Institute, Imperial College London, London, United Kingdom.
| | | | - Anmol Mohan
- Department of Medicine, Mayo Clinic, Rochester, USA
| | - Chadi Alraies
- Cardiovascular Institute, Detroit Medical Center, DMC Heart Hospital, Detroit, MI, USA
| |
Collapse
|
|
39
|
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.
Collapse
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
| |
Collapse
|
|
40
|
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.
Collapse
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
| |
Collapse
|
|
41
|
Yilmaz Kars M, Onal A, Turgut ZI, Akkar I, Cicek O, Dogan MH, Kizilarslanoglu MC. Comment on: Venous Thromboembolism in Patients Aged ≥ 90 Years: Trends in Clinical Features, Treatment, and Outcomes-RIETE Registry. J Am Geriatr Soc 2025. [PMID: 40260929 DOI: 10.1111/jgs.19483] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2025] [Revised: 03/11/2025] [Accepted: 03/17/2025] [Indexed: 04/24/2025]
Affiliation(s)
- Merve Yilmaz Kars
- Department of Internal Medicine, Division of Geriatrics, University of Health Sciences Türkiye, Hamidiye School of Medicine, Konya City Hospital, Konya, Türkiye
| | - Ahmet Onal
- Department of Internal Medicine, Division of Geriatrics, University of Health Sciences Türkiye, Hamidiye School of Medicine, Konya City Hospital, Konya, Türkiye
| | - Zeynep Iclal Turgut
- Department of Internal Medicine, Division of Geriatrics, University of Health Sciences Türkiye, Hamidiye School of Medicine, Konya City Hospital, Konya, Türkiye
| | - Ilyas Akkar
- Department of Internal Medicine, Division of Geriatrics, University of Health Sciences Türkiye, Hamidiye School of Medicine, Konya City Hospital, Konya, Türkiye
| | - Orhan Cicek
- Department of Internal Medicine, Division of Geriatrics, University of Health Sciences Türkiye, Hamidiye School of Medicine, Konya City Hospital, Konya, Türkiye
| | - Mustafa Hakan Dogan
- Department of Internal Medicine, Division of Geriatrics, University of Health Sciences Türkiye, Hamidiye School of Medicine, Konya City Hospital, Konya, Türkiye
| | - Muhammet Cemal Kizilarslanoglu
- Department of Internal Medicine, Division of Geriatrics, University of Health Sciences Türkiye, Hamidiye School of Medicine, Konya City Hospital, Konya, Türkiye
| |
Collapse
|
|
42
|
Abdel-Qadir H, Gunn M, Fang J, Odugbemi T, Jeong I, Austin PC, Dorian P, Jackevicius CA, Lee DS, Singh SM, Tu K, Ko DT. Risk for Stroke After Newly Diagnosed Atrial Fibrillation During Hospitalization for Other Primary Diagnoses : A Retrospective Cohort Study. Ann Intern Med 2025. [PMID: 40258280 DOI: 10.7326/annals-24-01967] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/23/2025] Open
Abstract
BACKGROUND Atrial fibrillation (AF) that is first diagnosed during hospitalization for other causes can subside with resolution of the inciting stressor. OBJECTIVE To describe the risk for stroke after newly diagnosed AF during hospitalization for other causes. DESIGN Population-based retrospective cohort study. SETTING Ontario, Canada. PARTICIPANTS Patients aged 66 years or older discharged alive from the hospital between April 2013 and March 2023 with a first diagnosis of AF. INTERVENTION Newly diagnosed AF during hospitalization for other causes, categorized into cardiac medical, noncardiac medical, cardiac surgical, and noncardiac surgical. MEASUREMENTS The primary outcome was hospitalization for stroke. The cumulative incidence function was used to estimate crude incidence, censoring on anticoagulant dispensation. Inverse probability of censoring weights were used to account for informative censoring. RESULTS Atrial fibrillation was diagnosed in 20 639 patients (mean age, 77.1 years; 58.1% male) while hospitalized for other causes: 8340 (40.4%) for noncardiac medical, 7097 (34.4%) for cardiac surgical, 3553 (17.2%) for noncardiac surgical, and 1649 (8.0%) for cardiac medical diagnoses. At 1 year, anticoagulants were being dispensed to 26.4% of patients with CHA2DS2-VA scores of 1 to 4 and 35.2% of those with CHA2DS2-VA scores of 5 to 8. The 1-year risk for stroke without anticoagulation was 1.3% (95% CI, 0.7% to 2.3%) for cardiac medical, 1.2% (CI, 0.9% to 1.5%) for noncardiac medical, 1.1% (CI, 0.8% to 1.7%) for noncardiac surgical, and 1.0% (CI, 0.7% to 1.3%) for cardiac surgical patients. Patients with CHA2DS2-VA scores of 1 to 4 had a 1-year stroke risk of 0.7% (CI, 0.6% to 1.0%) without anticoagulation, compared with 1.8% (CI, 1.4% to 2.2%) at CHA2DS2-VA scores of 5 to 8. LIMITATION Long-standing AF may have been misclassified as newly diagnosed, leading to overestimation of stroke risk. CONCLUSION Among patients with newly diagnosed AF during hospitalization for other causes, a substantial proportion with low CHA2DS2-VA scores receive anticoagulation, with modest increases in this proportion at higher scores. The stroke risk in patients with CHA2DS2-VA scores greater than 4 approximated the 2% threshold commonly used to initiate anticoagulation in AF. PRIMARY FUNDING SOURCE Canadian Cardiovascular Society.
Collapse
Affiliation(s)
- Husam Abdel-Qadir
- Women's College Hospital; University Health Network; ICES; Institute of Health Policy, Management and Evaluation, University of Toronto; and Department of Medicine, University of Toronto, Toronto, Ontario, Canada (H.A.-Q.)
| | - Madison Gunn
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada (M.G.)
| | - Jiming Fang
- ICES, Toronto, Ontario, Canada (J.F., T.O., I.J.)
| | | | - Irene Jeong
- ICES, Toronto, Ontario, Canada (J.F., T.O., I.J.)
| | - Peter C Austin
- ICES and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada (P.C.A.)
| | - Paul Dorian
- Department of Medicine, University of Toronto, and Division of Cardiology, Unity Health, Toronto, Ontario, Canada (P.D.)
| | - Cynthia A Jackevicius
- University Health Network; ICES; Institute of Health Policy, Management and Evaluation, University of Toronto; and College of Pharmacy, Western University of Health Sciences, Toronto, Ontario, Canada (C.A.J.)
| | - Douglas S Lee
- University Health Network; ICES; Institute of Health Policy, Management and Evaluation, University of Toronto; and Department of Medicine, University of Toronto, Toronto, Ontario, Canada (D.S.L.)
| | - Sheldon M Singh
- Department of Medicine, University of Toronto, and Schulich Heart Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (S.M.S.)
| | - Karen Tu
- University Health Network; Institute of Health Policy, Management and Evaluation, University of Toronto; North York General Hospital; and Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada (K.T.)
| | - Dennis T Ko
- ICES; Institute of Health Policy, Management and Evaluation, University of Toronto; Department of Medicine, University of Toronto; and Schulich Heart Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (D.T.K.)
| |
Collapse
|
|
43
|
Adetunji AO, Price J, Owusu H, Adewale EF, Adesina PA, Saliu TP, Zhu Z, Xedzro C, Asiamah E, Islam S. Mechanisms by which phytogenic extracts enhance livestock reproductive health: current insights and future directions. Front Vet Sci 2025; 12:1568577. [PMID: 40308693 PMCID: PMC12042781 DOI: 10.3389/fvets.2025.1568577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Accepted: 03/31/2025] [Indexed: 05/02/2025] Open
Abstract
Reproductive health is a critical determinant of livestock productivity and economic sustainability. However, it is often compromised by infectious diseases, environmental stressors, and nutritional deficits. Phytogenic extracts-bioactive compounds derived from medicinal plants-have emerged as sustainable alternatives to synthetic antibiotics and hormones, exhibiting antimicrobial, antioxidant, and immunomodulatory properties. These extracts influence key reproductive processes such as follicular development, oocyte maturation, and endometrial health while mitigating the detrimental effects of oxidative stress and pathogenic infections. Recent findings suggest that phytogenic extract can enhance reproductive performance, improve oocyte quality, and support pregnancy outcomes. Despite the growing body of evidence, optimal application strategies and the full breadth of their biological effects remain insufficiently explored. This review focuses on the molecular mechanisms modulated by phytogenic extracts, particularly in the context of hormone regulation, immune modulation, and oxidative stress mitigation. We also identify critical knowledge gaps and propose future research directions to optimize the use of phytogenic extracts as a sustainable approach to enhancing livestock reproductive health.
Collapse
Affiliation(s)
- Adedeji O. Adetunji
- Department of Agriculture, University of Arkansas at Pine Bluff, Pine Bluff, AR, United States
| | - Jacqueline Price
- Department of Agriculture, University of Arkansas at Pine Bluff, Pine Bluff, AR, United States
| | - Henrietta Owusu
- Department of Agriculture, University of Arkansas at Pine Bluff, Pine Bluff, AR, United States
| | - Esiosa F. Adewale
- Department of Biology, University of Louisville, Louisville, KY, United States
| | - Precious Adedayo Adesina
- National Center for Advancing Translational Sciences, Division for Pre-Clinical Innovation, National Institutes of Health, Bethesda, MD, United States
| | - Tolulope Peter Saliu
- Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, United States
| | - Zhendong Zhu
- College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, China
| | - Christian Xedzro
- Laboratory of Food Microbiology and Hygiene, Hiroshima University, Higashihiroshima, Japan
| | - Emmanuel Asiamah
- Department of Agriculture, University of Arkansas at Pine Bluff, Pine Bluff, AR, United States
| | - Shahidul Islam
- Department of Agriculture, University of Arkansas at Pine Bluff, Pine Bluff, AR, United States
| |
Collapse
|
|
44
|
Schaefer JK, Errickson J, Kong X, Ali MA, Chipalkatti N, Haymart B, Kaatz S, Krol GD, Sood SL, Froehlich JB, Barnes GD. A Comparison of Outcomes With Apixaban, Rivaroxaban, and Warfarin for Atrial Fibrillation and/or Venous Thromboembolism. JACC. ADVANCES 2025; 4:101714. [PMID: 40286370 DOI: 10.1016/j.jacadv.2025.101714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 01/20/2025] [Accepted: 02/27/2025] [Indexed: 04/29/2025]
Abstract
BACKGROUND Apixaban and rivaroxaban are commonly used direct oral anticoagulants for atrial fibrillation (AF) and venous thromboembolism (VTE). Both have been compared to warfarin, but there are insufficient comparative outcome data. OBJECTIVES The purpose of this study was to assess outcomes of apixaban, rivaroxaban, and warfarin. METHODS This is a registry-based cohort study with data from 6 centers in Michigan, 2009 to 2023. Patients were adults with AF and/or VTE with at least 3 months of follow-up. Outcomes included rates of bleeding, thrombosis, healthcare utilization, and death. RESULTS A total of 13,435 patients met the study inclusion criteria (average age 66.7 years, 58.0% on anticoagulation for AF, average follow-up 28.2 months). After matching, 2 groups of 3,527 patients on apixaban and warfarin were compared. Any bleeding was similar between groups, but major bleeding was less with apixaban. Thrombotic event rates were higher with apixaban. Mortality, rates of emergency room visits, and hospitalizations for bleeding were higher with warfarin. After matching, 1,395 patients on rivaroxaban were compared to 4,185 patients on warfarin. Any bleeding and major bleeding were higher with rivaroxaban. Thrombotic event rates were similar, aside from a higher rate of "other" thrombosis with rivaroxaban. After matching, 2 groups of 1,395 patients on apixaban and rivaroxaban were compared. Any bleeding, major bleeding, and mortality were higher with rivaroxaban. Thrombotic event rates were similar. CONCLUSIONS For patients with AF and/or VTE, we observed that bleeding was highest with rivaroxaban, followed by warfarin, and then apixaban. Rates of thrombosis were higher with apixaban than with warfarin, largely driven by "other" thrombotic events.
Collapse
Affiliation(s)
- Jordan K Schaefer
- Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
| | - Josh Errickson
- Consulting for Statistics, Computing, & Analytics Research, University of Michigan, Ann Arbor, Michigan, USA
| | - Xiaowen Kong
- Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Mona A Ali
- Department of Heart and Vascular Services, Corewell Health William Beaumont University Hospital, Royal Oak, Michigan, USA
| | - Naina Chipalkatti
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Brian Haymart
- Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Scott Kaatz
- Division of Hospital Medicine, Henry Ford Health, Detroit, Michigan, USA
| | - Gregory D Krol
- Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan, USA
| | - Suman L Sood
- Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - James B Froehlich
- Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Geoffrey D Barnes
- Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| |
Collapse
|
|
45
|
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.
Collapse
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.
| |
Collapse
|
|
46
|
Musialek P, Bonati LH, Bulbulia R, Halliday A, Bock B, Capoccia L, Eckstein HH, Grunwald IQ, Lip PL, Monteiro A, Paraskevas KI, Podlasek A, Rantner B, Rosenfield K, Siddiqui AH, Sillesen H, Van Herzeele I, Guzik TJ, Mazzolai L, Aboyans V, Lip GYH. Stroke risk management in carotid atherosclerotic disease: a clinical consensus statement of the ESC Council on Stroke and the ESC Working Group on Aorta and Peripheral Vascular Diseases. Cardiovasc Res 2025; 121:13-43. [PMID: 37632337 DOI: 10.1093/cvr/cvad135] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 08/20/2023] [Accepted: 08/21/2023] [Indexed: 08/28/2023] Open
Abstract
Carotid atherosclerotic disease continues to be an important cause of stroke, often disabling or fatal. Such strokes could be largely prevented through optimal medical therapy and carotid revascularization. Advancements in discovery research and imaging along with evidence from recent pharmacology and interventional clinical trials and registries and the progress in acute stroke management have markedly expanded the knowledge base for clinical decisions in carotid stenosis. Nevertheless, there is variability in carotid-related stroke prevention and management strategies across medical specialities. Optimal patient care can be achieved by (i) establishing a unified knowledge foundation and (ii) fostering multi-specialty collaborative guidelines. The emergent Neuro-Vascular Team concept, mirroring the multi-disciplinary Heart Team, embraces diverse specializations, tailors personalized, stratified medicine approaches to individual patient needs, and integrates innovative imaging and risk-assessment biomarkers. Proposed approach integrates collaboration of multiple specialists central to carotid artery stenosis management such as neurology, stroke medicine, cardiology, angiology, ophthalmology, vascular surgery, endovascular interventions, neuroradiology, and neurosurgery. Moreover, patient education regarding current treatment options, their risks and advantages, is pivotal, promoting patient's active role in clinical care decisions. This enables optimization of interventions ranging from lifestyle modification, carotid revascularization by stenting or endarterectomy, as well as pharmacological management including statins, novel lipid-lowering and antithrombotic strategies, and targeting inflammation and vascular dysfunction. This consensus document provides a harmonized multi-specialty approach to multi-morbidity prevention in carotid stenosis patients, based on comprehensive knowledge review, pinpointing research gaps in an evidence-based medicine approach. It aims to be a foundational tool for inter-disciplinary collaboration and prioritized patient-centric decision-making.
Collapse
Affiliation(s)
- Piotr Musialek
- Jagiellonian University Department of Cardiac and Vascular Diseases, St. John Paul II Hospital, ul. Pradnicka 80, 31-202 Krakow, Poland
| | | | - Richard Bulbulia
- Medical Research Council Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK
- Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK
| | - Alison Halliday
- Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK
| | | | - Laura Capoccia
- Department of Surgery 'Paride Stefanini', Policlinico Umberto I, 'Sapienza' University of Rome, Rome, Italy
| | - Hans-Henning Eckstein
- Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Iris Q Grunwald
- Department of Radiology, Ninewells Hospital, University of Dundee, Dundee, UK
- Tayside Innovation MedTech Ecosystem (TIME), Division of Imaging Science and Technology, University of Dundee, Dundee, UK
| | | | - Andre Monteiro
- Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, NY, USA
| | | | - Anna Podlasek
- Tayside Innovation MedTech Ecosystem (TIME), Division of Imaging Science and Technology, University of Dundee, Dundee, UK
- Division of Radiological and Imaging Sciences, University of Nottingham, Nottingham, UK
| | - Barbara Rantner
- Vascular Surgery Department, Ludwig Maximilian University Hospital, Campus Grosshadern, Munich, Germany
| | | | - Adnan H Siddiqui
- Department of Radiology, Jacobs School of Medicine and Biomedical Sciences, and Canon Stroke and Vascular Research Center, University at Buffalo, Buffalo, NY, USA
- Jacobs Institute, Buffalo, NY, USA
| | - Henrik Sillesen
- Department of Vascular Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Isabelle Van Herzeele
- Department of Thoracic and Vascular Surgery, Ghent University Hospital, Ghent, Belgium
| | - Tomasz J Guzik
- Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
- Department of Internal Medicine, Jagiellonian University Collegium Medicum, Krakow, Poland
| | - Lucia Mazzolai
- Department of Angiology, University Hospital Lausanne, Lausanne, Switzerland
| | - Victor Aboyans
- Department of Cardiology, CHRU Dupuytren Limoges, Limoges, France
| | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science at 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
| |
Collapse
|
|
47
|
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.
Collapse
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
| |
Collapse
|
|
48
|
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.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | | | - Antje Blank
- Internal Medicine IX, Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University, Medical Faculty Heidelberg/Heidelberg University Hospital, Heidelberg, Germany
| |
Collapse
|
|
49
|
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.
Collapse
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
| |
Collapse
|
|
50
|
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.
Collapse
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.
| |
Collapse
|