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Zergioti M, Kyriakou M, Papazoglou AS, Kartas A, Moysidis DV, Samaras A, Karagiannidis E, Kamperidis V, Ziakas A, Giannakoulas G. Oral Anticoagulation Choice and Dosage in Very Elderly Patients with Atrial Fibrillation. J Cardiovasc Dev Dis 2025; 12:86. [PMID: 40137084 PMCID: PMC11943373 DOI: 10.3390/jcdd12030086] [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: 01/18/2025] [Revised: 02/13/2025] [Accepted: 02/22/2025] [Indexed: 03/27/2025] Open
Abstract
BACKGROUND Selecting the optimal oral anticoagulation (OAC) therapy for elderly patients with atrial fibrillation (AF) remains challenging. Our real-world study investigates clinical factors guiding OAC prescription patterns and compares outcomes between full- and reduced-dose direct-acting oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in this demographic. METHODS This post hoc analysis of the MISOAC-AF trial focused on hospitalized AF patients aged ≥ 75 years prescribed OAC at discharge. Predictors of VKA and reduced DOAC dosing were identified using adjusted odds ratios (aORs). Cox regression models calculated adjusted hazard ratios (aHRs) for primary (all-cause mortality) and secondary outcomes (stroke, bleeding, AF or heart failure hospitalization, cardiovascular death). RESULTS Among 450 elderly patients, 63.6% received DOACs and 36.4% received VKAs. Higher CHA2DS2-VASc and HAS-BLED scores and antiplatelet use predicted VKA prescription. Hypertension, prior stroke, and bleeding history favored DOAC use. Advanced age and chronic kidney disease correlated with reduced DOAC dosing. Over a 3.7-year follow-up period, there was no significant difference in all-cause mortality between the DOAC and VKA groups (aHR 0.79, 95% CI 0.58-1.06) or between the full-dose and reduced-dose DOAC groups (aHR 0.96, 95% CI 0.60-1.53). Secondary analyses also did not yield statistically significant results in either comparison. CONCLUSIONS Clinical profile parameters in elderly AF patients predict VKA or DOAC use. Clinical outcomes were similar between different OAC therapies.
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Affiliation(s)
- Martha Zergioti
- Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.Z.); (M.K.); (A.S.P.); (A.K.); (V.K.); (A.Z.)
| | - Melina Kyriakou
- Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.Z.); (M.K.); (A.S.P.); (A.K.); (V.K.); (A.Z.)
| | - Andreas S. Papazoglou
- Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.Z.); (M.K.); (A.S.P.); (A.K.); (V.K.); (A.Z.)
| | - Anastasios Kartas
- Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.Z.); (M.K.); (A.S.P.); (A.K.); (V.K.); (A.Z.)
| | | | - Athanasios Samaras
- Second Department of Cardiology, Hippokration Hospital of Thessaloniki, 54643 Thessaloniki, Greece;
| | | | - Vasileios Kamperidis
- Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.Z.); (M.K.); (A.S.P.); (A.K.); (V.K.); (A.Z.)
- First Department of Cardiology, AHEPA University Hospital of Thessaloniki, 54636 Thessaloniki, Greece
| | - Antonios Ziakas
- Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.Z.); (M.K.); (A.S.P.); (A.K.); (V.K.); (A.Z.)
- First Department of Cardiology, AHEPA University Hospital of Thessaloniki, 54636 Thessaloniki, Greece
| | - George Giannakoulas
- Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.Z.); (M.K.); (A.S.P.); (A.K.); (V.K.); (A.Z.)
- First Department of Cardiology, AHEPA University Hospital of Thessaloniki, 54636 Thessaloniki, Greece
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Hao M, Wang Z, Gao H, Gao H, Cheng Z. Comparative Safety and Efficacy of Non-vitamin K Antagonist Oral Anticoagulants (NOACs) Versus Warfarin in Deep Vein Thrombosis (DVT) Treatment: A Meta-analysis. Cardiovasc Drugs Ther 2024:10.1007/s10557-024-07654-1. [PMID: 39729166 DOI: 10.1007/s10557-024-07654-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/19/2024] [Indexed: 12/28/2024]
Abstract
PURPOSE This meta-analysis aimed to conduct a systematic evaluation of the comparative efficacy and safety of new oral anticoagulants (NOACs) versus warfarin for the treatment of deep venous thrombosis (DVT). METHODS A systematic computerized search of databases including PubMed, Medline, Web of Science, Embase, Cochrane Library, and www. CLINICALTRIALS gov . was performed to gather research on the efficacy and safety of NOACs versus warfarin in the treatment of DVT, encompassing all records from the inception of each database through September 2024. The discrete data were presented as odds ratios (ORs) with their corresponding 95% confidence intervals (CIs), and the meta-analysis was executed utilizing the Review Manager 5.4.1 and Stata 16 softwares. RESULTS A comprehensive analysis of 16 studies encompassing 10,084 patients was conducted, with 6704 individuals in the experimental group receiving NOACs and 3380 in the control group treated with warfarin. The findings are as follows: (1) NOACs demonstrated enhanced treatment efficacy over warfarin, particularly in achieving vascular patency (OR = 1.57, 95% CI (1.09, 2.24), P = 0.01). (2) Regarding the incidence of major bleeding events (OR = 0.65, 95% CI (0.54, 0.78), P < 0.00001), other clinical adverse events-including pulmonary embolism, mortality, stroke, myocardial infarction and recurrent thrombosis (OR = 0.77, 95% CI (0.67, 0.88), P = 0.0002), and post-thrombotic syndrome (PTS) (OR = 0.62, 95% CI (0.47, 0.80), P = 0.0003); NOACs offered improved safety profiles in comparison to warfarin. Furthermore, subgroup analysis revealed that the preventive efficacy of NOACs against PTS improves with longer follow-up periods (P = 0.02). CONCLUSION NOACs have demonstrated superior efficacy and safety profiles in the treatment of DVT compared to traditional warfarin anticoagulant therapy. CLINICAL TRIAL REGISTRATION This project did not involve any clinical data collection; the data utilized were derived from articles published in PubMed.
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Affiliation(s)
- Manwei Hao
- Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun City, Jilin Province, P.R. China
| | - Zhongchao Wang
- Basic Medical Department, Changchun Medical College, Changchun City, Jilin Province, P.R. China
| | - Han Gao
- Basic Medical Department, Changchun Medical College, Changchun City, Jilin Province, P.R. China
| | - Haicheng Gao
- Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun City, Jilin Province, P.R. China.
| | - Zhihua Cheng
- Vascular Surgery Department, General Surgery Center, First Hospital of Jilin University, Changchun City, Jilin Province, P.R. China.
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Ren J, Wang N, Zhang X, Song F, Zheng X, Han X. A systematic review and meta-analysis of the morbidity of efficacy endpoints and bleeding events in elderly and young patients treated with the same dose rivaroxaban. Ann Hematol 2024; 103:4363-4373. [PMID: 38710878 DOI: 10.1007/s00277-024-05767-z] [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: 02/19/2024] [Accepted: 04/17/2024] [Indexed: 05/08/2024]
Abstract
Rivaroxaban is a new direct oral anticoagulant, and the same dose is recommended for older and young patients. However, recent real-world studies show that older patients may need dose adjustment to prevent major bleeding. At present, the evidence for dose adjustment in older patients is extremely limited with only a few reports on older atrial fibrillation patients. The aim of this study was to review the morbidity data of adverse events and bleeding events across all indications for older and young patients treated with the same dose of rivaroxaban to provide some support for dosage adjustment in older patients. The PubMed, EMBASE, ClinicalTrials, Cochrane and Web of Science databases were searched for randomized controlled trials (RCTs) published between January 1, 2005, and October 10, 2023. The primary outcomes were the morbidity of bleeding events and efficacy-related adverse events. Summary estimates were calculated using a random effects model. Eighteen RCTs were included in the qualitative analysis. The overall morbidity of primary efficacy endpoints was higher in older patients compared to the young patients (3.37% vs. 2.60%, χ2 = 5.24, p = 0.022). Similarly, a higher morbidity of bleeding was observed in older patients compared to the young patients (4.42% vs. 6.03%, χ2 = 13.22, p < 0.001). Among all indications, deep vein thrombosis, pulmonary embolism and atrial fibrillation were associated with the highest incidence of bleeding in older patients, suggesting that these patients may be most need dose adjustment. Patients older than 75 years may require extra attention to prevent bleeding. The same dose of rivaroxaban resulted in higher bleeding morbidity and morbidity of efficacy-related adverse events in older patients compared to the young patients. An individualized dose adjustment may be preferred for older patients rather than a fixed dose that fits all.
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Affiliation(s)
- Jianwei Ren
- Clinical Pharmacology Research Center, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Na Wang
- Clinical Pharmacology Research Center, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Xuan Zhang
- Clinical Pharmacology Research Center, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Fuyu Song
- Center for Food and Drug Inspection, National Medical Products Administration, Beijing, 100053, China
- NHC Key Laboratory of Mental Health, National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Peking University Institute of Mental Health, Peking University, Beijing, 100191, China
| | - Xin Zheng
- Clinical Pharmacology Research Center, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
| | - Xiaohong Han
- Clinical Pharmacology Research Center, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
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Spruit JR, de Vries TAC, Hemels MEW, Pisters R, de Groot JR, Jansen RWMM. Direct Oral Anticoagulants in Older and Frail Patients with Atrial Fibrillation: A Decade of Experience. Drugs Aging 2024; 41:725-740. [PMID: 39141209 PMCID: PMC11408570 DOI: 10.1007/s40266-024-01138-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/22/2024] [Indexed: 08/15/2024]
Abstract
INTRODUCTION Both the prevalence of atrial fibrillation (AF) and its subsequent use of direct oral anticoagulants (DOACs) are rapidly increasing in patients of older age. In the absence of contra-indications, guidelines advocate anticoagulation based on the CHA2DS2-VASc score for all AF patients aged 75 and above. However, some practitioners are hesitant to prescribe anticoagulants to older and frail patients due to perceived elevated bleeding risks. This review delves into the comparative treatment outcomes of DOACs versus vitamin K antagonists (VKAs) in older patients with AF, particularly focusing on those of advanced age, frailty, increased risk of falling, chronic kidney disease (CKD), or with a history of major bleeding. Additionally, considerations on the use of off-label DOAC doses, the role of left atrial appendage (LAA) closure and future developments in factor XIa-inhibitors will be discussed. RESULTS While strong evidence supports the use of DOACs in the vital older patients with nonvalvular AF, it remains scant in frail patient groups. There is some evidence from non-randomized studies suggesting that the effect of DOACs compared with VKAs is consistent between frail and nonfrail patients. However, recent findings from a single randomized trial showed increased bleeding risks but comparable thromboembolic outcomes in frail individuals switching from VKAs to DOACs. In patients with an increased risk of falling, data suggest no relevant interaction of increased risk of falling on the effectiveness and safety of DOACs compared with warfarin. Resuming oral anticoagulants in patients with Af after major bleeding seems to be beneficial. Off-label low-dose DOAC is often prescribed to patients who were underrepresented in larger randomized trails because of an elevated risk of bleeding or overexposure to DOACs, but its effect on clinical outcomes remains uncertain. CONCLUSIONS DOACs are the recommended oral anticoagulant for vital older patients with AF. The scarcity of data backing DOAC use in frail individuals, those with renal impairments, or significant bleeding history underscores the necessity for further investigation. However, existing evidence suggests at least similar effectiveness and safety and potential benefits for DOACs in these patient subsets. Therefore, there is no reason to suggest these patients should be treated differently than the established guidelines regarding anticoagulation.
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Affiliation(s)
- Jocelyn R Spruit
- Department of Geriatric Medicine, Northwest Clinics, Wilhelminalaan 12, 1815 JD, Alkmaar, The Netherlands.
| | - Tim A C de Vries
- Department of Cardiology, Rijnstate Hospital, Arnhem, The Netherlands
- Department of Clinical and Experimental Cardiology and Cardiothoracic Surgery, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Cardiovascular Sciences, Heart failure and Arrhythmias, Amsterdam, The Netherlands
- Department of Cardiology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Martin E W Hemels
- Department of Cardiology, Rijnstate Hospital, Arnhem, The Netherlands
- Department of Cardiology, Radboud University Hospital, Nijmegen, The Netherlands
| | - Ron Pisters
- Department of Cardiology, Rijnstate Hospital, Arnhem, The Netherlands
| | - Joris R de Groot
- Department of Clinical and Experimental Cardiology and Cardiothoracic Surgery, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Cardiovascular Sciences, Heart failure and Arrhythmias, Amsterdam, The Netherlands
- Department of Cardiology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - René W M M Jansen
- Department of Geriatric Medicine, Northwest Clinics, Wilhelminalaan 12, 1815 JD, Alkmaar, The Netherlands
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Ge G, Bo D, Jiang R, Zhao W, Lu Y. Oral anticoagulants increased 30-day survival in sepsis patients complicated with atrial fibrillation: a retrospective analysis from MIMIC-IV database. Front Cardiovasc Med 2024; 11:1322045. [PMID: 38304138 PMCID: PMC10830619 DOI: 10.3389/fcvm.2024.1322045] [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: 10/15/2023] [Accepted: 01/05/2024] [Indexed: 02/03/2024] Open
Abstract
Background The severity of sepsis is associated with systemic clotting activation. Atrial fibrillation (AF) is the most commonly observed arrhythmia in patients with sepsis and can lead to a poor prognosis. The aim of this study is to elucidate the association between oral anticoagulants and survival from septic patients complicated with AF. Methods The data of 8,828 septic patients, including 2,955 AF and 5,873 without AF, were all originated from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients with sepsis and AF are divided into OAC- group (n = 1,774) and OAC+ group (n = 1,181) based on OAC therapy. Septic patients with no AF were considered as the control group (n = 5,873, sepsis and no AF group). The main outcome endpoint was the survival rate of 30 day. The secondary outcome endpoint was the length of stay (LOS) from intensive care unit and hospital. Propensity score matching (PSM) was used to adjust the influence of superfluous factors, and a restricted mean survival time (RMST) analysis was used for calculating the benefit of survival time and survival rate. Analysis including univariate and multivariate logistic regression analysis was conducted to find prognosis-related predictors. Results After PSM, the OAC+group had a higher 30-day survival rate compared to the OAC- group (81.59% vs. 58.10%; P < 0.001) in the ICU. Despite the higher survival, the hospital LOS (14.65 days vs. 16.66 days; P = 0.15) and ICU LOS (6.93 days vs. 5.92 days; P = 0.02) were prolonged at OAC+ group than OAC- group. No difference was found in survival rate of 30 day between the sepsis patients using warfarin and patients using NOAC (85.60% vs. 79.84%, P = 0.12). The sepsis patients using warfarin had a prolonged LOS in ICU and hospital compared with the sepsis patients using NOAC. In the vasopressor subgroup, patients who received NOAC therapy were associated with a reduced 30-day survival rate (73.57% vs. 84.03%; P = 0.04) and reduced LOS in ICU and hospital than those on warfarin therapy. Conclusion This study demonstrated that oral anticoagulants may increase the 30-day survival rate of patients with sepsis and AF.
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Affiliation(s)
- Gaoyuan Ge
- Department of Cardiology, The Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, China
| | - Dan Bo
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Rongli Jiang
- Department of Geriatric, The Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, China
| | - Wei Zhao
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yao Lu
- Department of Cardiology, Xuzhou Central Hospital, Xuzhou Institute of Cardiovascular Disease, Xuzhou Clinical School of Nanjing Medical University, Xuzhou, Jiangsu, China
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Cao C, Xu Y, Jiang W, Wu S, Shen Y, Xia X, Wang L, Zhang H, Jiang H, Li X, Li X, Ye Y. Nomogram for predicting bleeding events in nonvalvular atrial fibrillation patients receiving rivaroxaban: A retrospective study. Health Sci Rep 2024; 7:e1792. [PMID: 38196572 PMCID: PMC10774492 DOI: 10.1002/hsr2.1792] [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: 08/01/2023] [Revised: 11/29/2023] [Accepted: 12/17/2023] [Indexed: 01/11/2024] Open
Abstract
Background and Aims To construct a bleeding events prediction model of nonvalvular atrial fibrillation (NVAF) patients receiving rivaroxaban. Methods We conducted a retrospective cohort study in patients with NVAF who received rivaroxaban from June 2017 to March 2019. Demographic information and clinical characteristics were obtained from the electronic medical system. Univariate analysis was used to find the primary predictive factors of bleeding events in patients receiving rivaroxaban. Multiple analysis was conducted to screen the primary independent predictive factors selected from the univariate analysis. Finally, the independent influencing factors were applied to build a prediction model by using R software; then, a nomogram was established according to the selected variables visually, and the sensitivity and specificity of the model was evaluated. Results Twelve primary predictive factors were selected by univariate analysis from 46 variables, and multivariate analysis showed that older age, higher prothrombin time (PT) values, history of heart failure and stroke were independent risk factors of bleeding events. The area under curve (AUC) for this novel nomogram model was 0.828 (95% CI: 0.763-0.894). The mean AUC over 10-fold stratified cross-validation was 0.787, and subgroup analysis validation also showed a satisfied AUC. In addition, the decision curve analysis showed that the PT in combination with CHA2DS2-VASc and HASBLED was more practical and accurate for predicting bleeding events than using CHA2DS2-VASc and HASBLED alone. Conclusions PT in combination with CHA2DS2-VASc and HASBLED could be considered as a more practical and accurate method for predicting bleeding events in patients taking rivaroxaban.
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Affiliation(s)
- Chang Cao
- Department of Pharmacy, Zhongshan Hospital (Xiamen)Fudan UniversityXiamenChina
- Department of Pharmacy, Zhongshan HospitalFudan UniversityShanghaiChina
| | - Yijiao Xu
- Department of Respiration, Zhongshan Hospital (Xiamen)Fudan UniversityXiamenChina
| | - Weiwen Jiang
- Department of Pharmacy, Zhongshan Hospital (Xiamen)Fudan UniversityXiamenChina
- Department of Pharmacy, Zhongshan HospitalFudan UniversityShanghaiChina
| | - Shujing Wu
- Department of Cardiology, Zhongshan Hospital (Xiamen)Fudan UniversityXiamenChina
| | - Yun Shen
- Department of Pharmacy, Zhongshan Hospital (Xiamen)Fudan UniversityXiamenChina
- Department of Pharmacy, Zhongshan HospitalFudan UniversityShanghaiChina
| | - Xiaotong Xia
- Department of Pharmacy, Zhongshan Hospital (Xiamen)Fudan UniversityXiamenChina
| | - Lumin Wang
- Department of Pharmacy, Zhongshan Hospital (Xiamen)Fudan UniversityXiamenChina
| | - Huijun Zhang
- Department of Respiration, Zhongshan Hospital (Xiamen)Fudan UniversityXiamenChina
| | - Hongni Jiang
- Department of Respiration, Zhongshan Hospital (Xiamen)Fudan UniversityXiamenChina
| | - Xiaoyu Li
- Department of Pharmacy, Zhongshan Hospital (Xiamen)Fudan UniversityXiamenChina
- Department of Pharmacy, Zhongshan HospitalFudan UniversityShanghaiChina
| | - Xiaoye Li
- Department of Pharmacy, Zhongshan HospitalFudan UniversityShanghaiChina
| | - Yanrong Ye
- Department of Pharmacy, Zhongshan Hospital (Xiamen)Fudan UniversityXiamenChina
- Department of Pharmacy, Zhongshan HospitalFudan UniversityShanghaiChina
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Branco DR, Alves M, Severiano E Sousa C, Costa J, Ferreira JJ, Caldeira D. Direct oral anticoagulants vs vitamin K antagonist on dementia risk in atrial fibrillation: systematic review with meta-analysis. J Thromb Thrombolysis 2023; 56:474-484. [PMID: 37405677 PMCID: PMC10439029 DOI: 10.1007/s11239-023-02843-5] [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] [Accepted: 06/03/2023] [Indexed: 07/06/2023]
Abstract
Oral anticoagulation significantly reduces the incidence of dementia in atrial fibrillation patients. However, this protective effect has not been compared between Direct Oral Anticoagulants (DOAC) and Vitamin K antagonists' anticoagulants (VKA). We conducted an electronic search for potentially eligible studies through the bibliographic databases MEDLINE, CENTRAL, ClinicalTrials.gov, EMBASE and Web of Science. The outcome of interest was dementia. Random-effects meta-analysis was performed. Nine observational studies were included and 1,175,609 atrial fibrillation patients were enrolled. DOAC therapy was associated with a significant reduction when compared with patients under VKA therapy (hazard ratio 0.89; 95% confidence interval 0.80-0.99). The grade of confidence of our results was very low due to the risk of bias. DOAC therapy is associated with a significant decrease in the risk of dementia when compared with VKA therapy. However, the low certainty of the evidence along with the paucityof clinical trials dedicated to answering this important question underscores a need for global clinical research initiatives.
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Affiliation(s)
- Diogo R Branco
- Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Mariana Alves
- Serviço de Medicina III, Hospital Pulido Valente, CHLN, Lisbon, Portugal
- Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal
- Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal
| | - Catarina Severiano E Sousa
- Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal
- Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal
| | - João Costa
- Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal
- Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal
| | - Joaquim J Ferreira
- Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal
- Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal
- CNS-Campus Neurológico Senior, Torres Vedras, Portugal
| | - Daniel Caldeira
- Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal.
- Centro Cardiovascular da Universidade de Lisboa-(CCUL@RISE), CAML, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
- Serviço de Cardiologia, Hospital Universitário de Santa Maria-CHULN, Lisbon, Portugal.
- Centro de Estudos de Medicina Baseada na Evidência (CEMBE), Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
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Pundi K, Perino AC, Fan J, Din N, Szummer K, Heidenreich P, Turakhia MP. Association of CHA 2DS 2-VASc and HAS-BLED to frailty and frail outcomes: From the TREAT-AF study. Am Heart J 2023; 261:85-94. [PMID: 37024025 DOI: 10.1016/j.ahj.2023.03.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 03/24/2023] [Accepted: 03/29/2023] [Indexed: 05/26/2023]
Abstract
BACKGROUND Morbidity and mortality associated with high CHA2DS2-VASc and HAS-BLED scores is not specific to atrial fibrillation (AF). Frailty could be an important contributor to this morbidity and mortality while being mechanistically independent from AF. We sought to evaluate the association of stroke and bleeding risk to noncardiovascular frail events and the association of stroke prevention therapy to outcomes in frail patients with AF. METHODS Using the TREAT-AF (The Retrospective Evaluation and Assessment of Therapies in AF) study from the Veterans Health Administration, we identified patients with newly diagnosed AF from 2004 to 2014. Baseline frailty was identified using a previously validated claims-based index requiring ≥2 of 12 ICD-9 diagnoses. Logistic regressions modeled the association between CHA2DS2-VASc and modified HAS-BLED and frailty. Cox proportional hazard regressions were used to evaluate the association between CHA2DS2-VASc and modified HAS-BLED and a composite of noncardiovascular frail events (fractures, urinary tract infections, bacterial pneumonia, or dehydration). We also evaluated the association of oral anticoagulant (OAC) use with stroke, bleeding, and 1-year mortality in frail patients and non-frail patients. RESULTS In 213,435 patients (age 70 ± 11; 98% male; CHA2DS2-VASc 2.4 ± 1.7) with AF, 8,498 (4%) were frail. CHA2DS2-VASc > 0 and HAS-BLED > 0 were strongly associated with frailty (odds ratio [OR] 13.3 (95% CI: 11.6-15.2) for CHA2DS2-VASc 4+ and OR 13.4 (10.2-17.5) for HAS-BLED 3+). After adjusting for covariates, CHA2DS2-VASc, and HAS-BLED > 0 were associated with higher risk of non-cardiovascular frail events (hazard ratio [HR] 2.1 (95% CI: 2.0-2.2) for CHA2DS2-VASc 4+ and HR 1.4 (95% CI: 1.3-1.5) for HAS-BLED 3+). In frail patients, OAC use was associated with significantly lower risk of 1-year mortality (HR 0.82; 95% CI 0.72-0.94, P = .0031) but did not reach significance for risk of stroke (HR 0.80; 95% CI 0.55-1.18, P = .26) or major bleeding (HR 1.08; 95% CI 0.93-1.25, P = .34). CONCLUSIONS High CHA2DS2-VASc and HAS-BLED scores are strongly associated with frailty. However, in frail patients, OAC use was associated with reduction in 1-year mortality. For this challenging clinical population with competing risks of frailty and frail events, focused prospective studies are needed to support clinical decision-making. Until then, careful evaluation of frailty should inform shared decision-making.
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Affiliation(s)
- Krishna Pundi
- Department of Medicine, Stanford University School of Medicine, Stanford, CA.
| | - Alexander C Perino
- Department of Medicine, Stanford University School of Medicine, Stanford, CA; Center for Digital Health, Stanford University School of Medicine, Stanford, CA
| | - Jun Fan
- Veterans Affairs Palo Alto Health Care System, Palo Alto, CA
| | - Natasha Din
- Veterans Affairs Palo Alto Health Care System, Palo Alto, CA
| | - Karolina Szummer
- Karolinska University Hospital, Theme Heart and Vessel; Karolinska Institutet, Stockholm, Sweden
| | - Paul Heidenreich
- Department of Medicine, Stanford University School of Medicine, Stanford, CA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA
| | - Mintu P Turakhia
- Department of Medicine, Stanford University School of Medicine, Stanford, CA; Center for Digital Health, Stanford University School of Medicine, Stanford, CA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA
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9
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Lee KH, Chen YF, Yeh WY, Yeh JT, Yang TH, Chou CY, Chang YL, Wang WT, Chiang CE, Chen CH, Cheng HM. Optimal stroke preventive strategy for patients aged 80 years or older with atrial fibrillation: a systematic review with traditional and network meta-analysis. Age Ageing 2022; 51:6931851. [PMID: 36571776 DOI: 10.1093/ageing/afac292] [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: 07/28/2022] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND An optimal antithrombotic strategy for patients aged 80 years or older with atrial fibrillation (AF) remains elusive. OBJECTIVE Using a systematic review with traditional and network meta-analysis, we investigated outcomes in AF patients ≥80 years treated with different antithrombotic strategies. METHODS We searched eligible randomised controlled trials (RCTs) and observational studies from MEDLINE, EMBASE, Cochrane Library and Web of Science databases from inception to 16 December 2021. Research comparing treatment outcomes of novel oral anticoagulants (NOACs), aspirin, vitamin K antagonists (VKAs) or no oral anticoagulant/placebo therapy in patients ≥80 years with AF were included. Outcomes were stroke or systemic embolism (SSE), major bleeding, all-cause mortality, intracranial bleeding (ICH) and gastrointestinal bleeding. Traditional and network meta-analyses were performed. Net clinical benefit integrating SSE and major bleeding was calculated. RESULTS Fifty-three studies were identified for analysis. In the meta-analysis of RCTs, risk of SSE (risk ratio [RR]: 0.82; 95% confidence interval [CI]: 0.73-0.99) and ICH (RR: 0.38; 95% CI: 0.28-0.52) was significantly reduced when NOACs were compared with VKAs. Network meta-analysis of RCTs demonstrated that edoxaban (P-score: 0.8976) and apixaban (P-score: 0.8528) outperformed other antithrombotic therapies by showing a lower major bleeding risk and better net clinical benefit. Both traditional and network meta-analyses from RCTs combining with observational studies showed consistent results. CONCLUSIONS In patients aged 80 years or older with AF, NOACs have better outcomes than VKAs regarding efficacy and safety profiles. Edoxaban and apixaban may be preferred treatment options since they are safer than other antithrombotic strategies.
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Affiliation(s)
- Kun-Han Lee
- Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ying-Fan Chen
- Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Wan-Yu Yeh
- Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan.,Division of Evidence-based Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jiunn-Tyng Yeh
- Department of Internal Medicine, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
| | - Tzu-Han Yang
- Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chian-Ying Chou
- Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Pharmacy, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yuh-Lih Chang
- Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Pharmacy, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Wei-Ting Wang
- Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chern-En Chiang
- School of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan.,General Clinical Research Center, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chen-Huan Chen
- Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan.,Institute of Public Health, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan
| | - Hao-Min Cheng
- Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan.,Division of Evidence-based Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan.,Institute of Public Health, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan
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10
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Abrignani MG, Lombardo A, Braschi A, Renda N, Abrignani V, Lombardo RM. Time trends in antithrombotic therapy prescription patterns: Real-world monocentric study in hospitalized patients with atrial fibrillation. World J Cardiol 2022; 14:576-598. [PMID: 36483763 PMCID: PMC9724000 DOI: 10.4330/wjc.v14.i11.576] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Revised: 07/04/2022] [Accepted: 10/27/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Since 2010, the European Society of Cardiology has extended prescription criteria for oral antithrombotic therapy (OAT) in atrial fibrillation (AF). Direct oral anticoagulants (DOACs) were upgraded from an IIAa recommendation in 2012 to an IA in 2016. In real-world scenarios, however, OAC prescription is still suboptimal, mainly for DOACs. AIM To evaluate OAT temporal prescription patterns in a cohort of patients hospitalized with AF in a Cardiology Department. METHODS A retrospective observational study was conducted on a cohort of hospitalized patients in a secondary setting (Trapani, Italy) from 2010 to 2021 with AF as the main or secondary diagnosis. For 4089 consecutive patients, the variables extracted from the Cardiology department database were: Sex, age, time of hospitalization, antithrombotic therapy (warfarin, acenocoumarol, apixaban, dabigatran, edoxaban, rivaroxaban, aspirin, clopidogrel, other antiplatelet agents, low molecular weight heparin, and fondaparinux), diagnosis at discharge and used resources. Basal features are presented as percentage values for categorized variables and as mean +/- SD for categorized once. RESULTS From January 1st, 2010 to October 6th, 2021, 25132 patients were hospitalized in our department; 4089 (16.27%, mean age 75.59+/-10.82) were discharged with AF diagnosis; of them, 2245 were males (54.81%, mean age 73.56+/-11.45) and 1851 females (45.19%, mean age 78.06+/-9.47). Average length of stay was 5.76+/-4.88 days; 154 patients died and 88 were moved to other Departments/Structures. AF was the main diagnosis in 899 patients (21.94%). The most frequent main diagnosis in patients with AF was acute myocardial infarction (1973 discharges, 48.19%). The most frequent secondary cardiac diagnosis was chronic coronary syndrome (1864 discharges, 45.51%), and the most frequent secondary associated condition was arterial hypertension (1010 discharges, 24.66%). For the analysis of antithrombotic treatments, the final sample included 3067 patients, after excluding in-hospital deaths, transferred out or self-discharged patients, as well as discharges lacking indications for prescribed treatments. OAC treatment increased significantly (35.63% in 2010-2012 vs 61.18% in 2019-2021, +25.55%, P < 0.0001), in spite of any antiplatelet agent use. This rise was due to increasing use of DOACs, with or without antiplatelet agents, from 3.04% in 2013-2015 to 50.06% in 2019-2021 (+47.02%, P < 0.0001) and was greater for factor Xa inhibitors, especially apixaban. In addition, treatment with a vitamin K antagonist, in spite of any antiplatelet agent use, decreased from 35.63% in 2010-2012 to 11.12% in 2019-2021 (-24.48%, P < 0.0001), as well as any antiplatelet therapy, alone or in double combination, (49.18% in 2010-2012 vs 34.18% in 2019-2021, -15.00%, P < 0.0001); and patients not receiving antithrombotic therapy declined with time (14.58% in 2010-2012 vs 1.97% in 2021, P < 0.0001). CONCLUSION Real-world patients with AF are elderly and affected by cardiovascular and non-cardiovascular diseases. The percentage of patients on OAT and DOACs increased. These data suggest a slow, gradual guidelines implementation process.
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Affiliation(s)
- Maurizio Giuseppe Abrignani
- Operative Unit of Cardiology, Department of Medicine, S. Antonio Abate Hospital of Trapani, ASP Trapani, Trapani 91100, Trapani, Italy.
| | - Alberto Lombardo
- Operative Unit of Cardiology, Department of Medicine, S. Antonio Abate Hospital of Trapani, ASP Trapani, Trapani 91100, Trapani, Italy
| | - Annabella Braschi
- Department of Psychology, Educational Science and Human Movement, University of Palermo, Palermo 90100, Palermo, Italy
| | - Nicolò Renda
- Department of Medicine and Surgery, University of Parma, Parma 43100, Parma, Italy
| | - Vincenzo Abrignani
- Operative Unit of Internal Medicine with Stroke Care, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE) "G. D'Alessandro", University of Palermo, Palermo 90100, Palermo, Italy
| | - Renzo M Lombardo
- Department of Cardiology, Operative Unit of Cardiology, Department of Medicine, S. Antonio Abate Hospital of Trapani, Trapani 91100, Trapani, Italy
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11
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Sun B, Chen RR, Gao C, Tao L. Comparison of outcomes between novel oral anticoagulants and warfarin monotherapy in patients with left atrial appendage closure: A systematic review and meta-analysis. Front Cardiovasc Med 2022; 9:1023941. [PMID: 36352853 PMCID: PMC9639703 DOI: 10.3389/fcvm.2022.1023941] [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: 08/20/2022] [Accepted: 10/06/2022] [Indexed: 11/23/2022] Open
Abstract
Background Pivotal trials of percutaneous left atrial appendage closure (LAAC) used dedicated post-procedure antithrombotic protocols. However, there is no consensus on the selection of new oral anticoagulants (NOAC) and warfarin monotherapy after LAAC. This study aims to compare NOAC with warfarin monotherapy for efficacy and safety in patients undergoing LAAC. Methods A database search was conducted using PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov for trials that compared NOAC with warfarin monotherapy after LAAC. The effective outcomes included any major adverse events (all-cause death, stroke, major bleeding) and their individual components. Safety outcomes included all-cause death, major bleeding, total bleeding, DRT, and PDL >5 mm. Results We included 10 non-randomized clinical trials with 10,337 patients, of whom 4,960 patients received NOAC, while 5,377 patients received warfarin. There were no statistically significant differences in any major adverse events (LogOR: -0.11, 95% CI: -0.27, 0.04, P = 0.16), stroke (LogOR: 0.00, 95% CI: -0.42, 0.42, P = 1.00), all-cause death (LogOR: -0.23, 95% CI: -0.48, 0.02, P = 0.07), major bleeding (LogOR: -0.22, 95% CI: -0.45, 0.01, P = 0.06). NOAC was associated with a significant reduction in total bleeding (LogOR: -1.01, 95% CI: -1.47, -0.55, P < 0.0001) compared to warfarin. No statistically significant differences were found in DRT (LogOR: -0.19, 95% CI: -0.15, 0.52, P = 0.27) and PDL >5 mm (LogOR: 0.19, 95% CI: -0.33, 0.72, P = 0.47). Meta-regression and subgroup analysis showed that total bleeding (LogOR: -1.56, 95% CI: -2.15, -0.97, P < 0.001) was significantly lower in the NOAC group in the subgroup of <75 y. Conclusion After LAAC, NOAC monotherapy was associated with a lower risk of bleeding compared to warfarin monotherapy for 45 days. There was no significant difference between NOAC and warfarin in terms of other results. Systematic review registration www.york.ac.uk/inst/crd, identifier: CRD42022361244.
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Affiliation(s)
- Bing Sun
- Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China
| | - Rui Rui Chen
- Department of Cardiology, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Chao Gao
- Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China
| | - Ling Tao
- Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China
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12
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Bories M, Bouzillé G, Cuggia M, Le Corre P. Drug–Drug Interactions with Oral Anticoagulants as Potentially Inappropriate Medications: Prevalence and Outcomes in Elderly Patients in Primary Care and Hospital Settings. Pharmaceutics 2022; 14:pharmaceutics14071410. [PMID: 35890305 PMCID: PMC9325322 DOI: 10.3390/pharmaceutics14071410] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 06/24/2022] [Accepted: 06/29/2022] [Indexed: 02/01/2023] Open
Abstract
Direct oral anticoagulants and vitamin K antagonists are considered as potentially inappropriate medications (PIM) in several situations according to Beers Criteria. Drug–drug interactions (DDI) occurring specifically with these oral anticoagulants considered PIM (PIM–DDI) is an issue since it could enhance their inappropriate character and lead to adverse drug events, such as bleeding events. The aim of this study was (1) to describe the prevalence of oral anticoagulants as PIM, DDI and PIM–DDI in elderly patients in primary care and during hospitalization and (2) to evaluate their potential impact on the clinical outcomes by predicting hospitalization for bleeding events using machine learning methods. This retrospective study based on the linkage between a primary care database and a hospital data warehouse allowed us to display the oral anticoagulant treatment pathway. The prevalence of PIM was similar between primary care and hospital setting (22.9% and 20.9%), whereas the prevalence of DDI and PIM–DDI were slightly higher during hospitalization (47.2% vs. 58.9% and 19.5% vs. 23.5%). Concerning mechanisms, combined with CYP3A4–P-gp interactions as PIM–DDI, were among the most prevalent in patients with bleeding events. Although PIM, DDI and PIM–DDI did not appeared as major predictors of bleeding events, they should be considered since they are the only factors that can be optimized by pharmacist and clinicians.
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Affiliation(s)
- Mathilde Bories
- Pôle Pharmacie, Service Hospitalo-Universitaire de Pharmacie, CHU de Rennes, 35033 Rennes, France;
- CHU Rennes, INSERM, LTSI-UMR 1099, Univ Rennes, 35000 Rennes, France; (G.B.); (M.C.)
- Laboratoire de Biopharmacie et Pharmacie Clinique, Faculté de Pharmacie, Université de Rennes 1, 35043 Rennes, France
| | - Guillaume Bouzillé
- CHU Rennes, INSERM, LTSI-UMR 1099, Univ Rennes, 35000 Rennes, France; (G.B.); (M.C.)
| | - Marc Cuggia
- CHU Rennes, INSERM, LTSI-UMR 1099, Univ Rennes, 35000 Rennes, France; (G.B.); (M.C.)
| | - Pascal Le Corre
- Pôle Pharmacie, Service Hospitalo-Universitaire de Pharmacie, CHU de Rennes, 35033 Rennes, France;
- Laboratoire de Biopharmacie et Pharmacie Clinique, Faculté de Pharmacie, Université de Rennes 1, 35043 Rennes, France
- CHU Rennes, INSERM, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail)-UMR_S 1085, Univ Rennes, 35000 Rennes, France
- Correspondence:
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13
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Liu F, Zhang Y, Luo J, Zhou Y. Intraocular Bleeding in Patients With Atrial Fibrillation Treated With NOACs VS. Warfarin: A Systematic Review and Meta-Analysis. Front Cardiovasc Med 2022; 9:813419. [PMID: 35722107 PMCID: PMC9199492 DOI: 10.3389/fcvm.2022.813419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 05/02/2022] [Indexed: 11/25/2022] Open
Abstract
Background Intraocular bleeding is a devastating adverse event for patients with atrial fibrillation (AF) receiving anticoagulant therapy. It is unknown whether non-vitamin K oral anticoagulants (NOACs) compared with warfarin can reduce the risk of intraocular bleeding in patients with AF. Herein, we conducted a meta-analysis to evaluate the effect of NOACs vs. warfarin on intraocular bleeding in the AF population. Methods Studies were systematically searched from the Embase, PubMed, and Cochrane databases until April 2022. We included studies if they enrolled patients with AF and compared the intraocular bleeding risk between NOACs and warfarin and if they were randomized controlled trials (RCTs) or observational cohort studies. The random-effects model was chosen to evaluate the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Results A total of 193,980 patients with AF from 5 randomized controlled trials (RCTs) and 1 cohort study were included. The incidence of intraocular bleeding among AF patients treated with warfarin and NOACs was 0.87% (n = 501/57346) and 0.61% (n = 836/136634), respectively. In the pooled analysis with the random-effects model, the use of NOACs was not significantly associated with the risk of intraocular bleeding (OR = 0.74; 95% CI 0.52–1.04, P = 0.08) compared with warfarin use. In addition, the sensitivity analysis with the fixed-effects model suggested that NOAC users had a lower incidence of intraocular bleeding than patients with warfarin (OR = 0.57; 95% CI 0.51–0.63, P < 0.00001). Conclusions Our current meta-analysis suggested that the use of NOACs had no increase in the incidence of intraocular bleeding compared with warfarin use in patients with AF. Whether the use of NOACs is superior to warfarin needs more research to confirm.
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Affiliation(s)
- Fuwei Liu
- Department of Cardiology, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, China
- *Correspondence: Fuwei Liu
| | - Yupei Zhang
- Second Clinical Medical College, Nanchang University, Nanchang, China
| | - Jun Luo
- Department of Cardiology, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, China
- Jun Luo
| | - Yue Zhou
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
- Yue Zhou
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14
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Bonanad C, García-Blas S, Torres Llergo J, Fernández-Olmo R, Díez-Villanueva P, Ariza-Solé A, Martínez-Sellés M, Raposeiras S, Ayesta A, Bertomeu-González V, Tarazona Santabalbina F, Facila L, Vivas D, Gabaldón-Pérez A, Bodi V, Nuñez J, Cordero A. Direct Oral Anticoagulants versus Warfarin in Octogenarians with Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis. J Clin Med 2021; 10:5268. [PMID: 34830548 PMCID: PMC8618042 DOI: 10.3390/jcm10225268] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 11/04/2021] [Accepted: 11/05/2021] [Indexed: 11/17/2022] Open
Abstract
Direct oral anticoagulants (DOACs) have been demonstrated to be more effective and safer than vitamin-K antagonist (VKA) for stroke prevention in patients with nonvalvular atrial fibrillation (AF). This meta-analysis aims to assess the effect of DOACS vs. VKA in patients ≥ 80 and AF. Primary endpoints were stroke or systemic embolism and all-cause death. Secondary endpoints included major bleeding, intracranial bleeding, and gastrointestinal bleeding. A random-effects model was selected due to significant heterogeneity. A total of 147,067 patients from 16 studies were included, 71,913 (48.90%) treated with DOACs and 75,154 with VKA (51.10%). The stroke rate was significantly lower in DOACs group compared with warfarin group (Relative risk (RR): 0.72; 95% confidence interval (CI): 0.63-0.82; p < 0.001). All-cause mortality was significantly lower in DOACs group compared with warfarin group (RR: 0.82; 95% CI: 0.70-0.96; p = 0.012). Compared to warfarin, DOACs were not associated with reductions in major bleeding (RR: 0.85, 95% CI 0.69-1.04; p = 0.108) or gastrointestinal bleeding risk (RR: 1.08, 95% CI 0.76-1.53; p = 0.678) but a 43% reduction of intracranial bleeding (RR: 0.47, IC 95% 0.36-0.60; p < 0.001) was observed. Our meta-analysis demonstrates that DOACs are effective and safe with statistical superiority when compared with warfarin in octogenarians with AF.
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Affiliation(s)
- Clara Bonanad
- Servicio de Cardiología, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain; (C.B.); (S.G.-B.); (A.G.-P.); (V.B.); (J.N.)
- Instituto de Investigación Sanitaria INCLIVA, 46010 Valencia, Spain
- Department of Medicine, Medicine Faculty, 46010 Valencia, Spain
| | - Sergio García-Blas
- Servicio de Cardiología, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain; (C.B.); (S.G.-B.); (A.G.-P.); (V.B.); (J.N.)
- Instituto de Investigación Sanitaria INCLIVA, 46010 Valencia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV), 28029 Madrid, Spain; (M.M.-S.); (V.B.-G.)
| | - Javier Torres Llergo
- Cardiology Department, Hospital Universitario de Jaén, 23007 Jaén, Spain; (J.T.L.); (R.F.-O.)
| | - Rosa Fernández-Olmo
- Cardiology Department, Hospital Universitario de Jaén, 23007 Jaén, Spain; (J.T.L.); (R.F.-O.)
| | | | - Albert Ariza-Solé
- Cardiology Department, Hospital Universitari de Bellvitge, 08907 L’Hospitalet de Llobregat, Spain;
| | - Manuel Martínez-Sellés
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV), 28029 Madrid, Spain; (M.M.-S.); (V.B.-G.)
- Cardiology Department, Hospital Universitario Gregorio Marañón, 28007 Madrid, Spain
| | - Sergio Raposeiras
- Cardiology Department, Hospital Álvaro Cunqueiro, 36213 Vigo, Spain;
| | - Ana Ayesta
- Cardiology Department, Hospital Central de Asturias, 33011 Oviedo, Spain;
| | - Vicente Bertomeu-González
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV), 28029 Madrid, Spain; (M.M.-S.); (V.B.-G.)
- Cardiology Department, Hospital Universitario de San Joan, 03550 Alicante, Spain
- Department of Clinical Medicine, Universidad Miguel Hernandez, 03550 Alicante, Spain
| | | | - Lorenzo Facila
- Cardiology Department, Hospital General Universitario de Valencia, 46014 Valencia, Spain;
| | - David Vivas
- Instituto Cardiovascular, Hospital Clínico San Carlos, 28040 Madrid, Spain;
| | - Ana Gabaldón-Pérez
- Servicio de Cardiología, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain; (C.B.); (S.G.-B.); (A.G.-P.); (V.B.); (J.N.)
- Instituto de Investigación Sanitaria INCLIVA, 46010 Valencia, Spain
| | - Vicente Bodi
- Servicio de Cardiología, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain; (C.B.); (S.G.-B.); (A.G.-P.); (V.B.); (J.N.)
- Instituto de Investigación Sanitaria INCLIVA, 46010 Valencia, Spain
- Department of Medicine, Medicine Faculty, 46010 Valencia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV), 28029 Madrid, Spain; (M.M.-S.); (V.B.-G.)
| | - Julio Nuñez
- Servicio de Cardiología, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain; (C.B.); (S.G.-B.); (A.G.-P.); (V.B.); (J.N.)
- Instituto de Investigación Sanitaria INCLIVA, 46010 Valencia, Spain
- Department of Medicine, Medicine Faculty, 46010 Valencia, Spain
| | - Alberto Cordero
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV), 28029 Madrid, Spain; (M.M.-S.); (V.B.-G.)
- Cardiology Department, Hospital Universitario de San Joan, 03550 Alicante, Spain
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15
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Papanastasiou A, Kartas A, Samaras A, Vrana E, Papazoglou A, Moysidis DV, Baroutidou A, Botis M, Liampas E, Vouloagkas I, Mareti E, Karagiannidis E, Karvounis H, Tzikas A, Giannakoulas G. Oral anticoagulation patterns and prognosis in octogenarian patients with atrial fibrillation. J Thromb Thrombolysis 2021; 53:851-860. [PMID: 34562201 DOI: 10.1007/s11239-021-02571-8] [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] [Accepted: 09/08/2021] [Indexed: 11/28/2022]
Abstract
The relationship between oral anticoagulants (OACs) and prognosis in elderly patients with atrial fibrillation (AF) has not been adequately explored. In this retrospective cohort study, we identified subjects aged over 80 from a database of 1140 AF patients discharged from the cardiology ward of a single tertiary center between 2015 and 2018. We examined the OAC treatment of octogenarian patients at discharge [VKA (vitamin K antagonist), NOAC (non-vitamin K antagonist oral anticoagulant), no OAC treatment]. We analyzed follow-up data of patients on OAC at discharge. The primary endpoint was all-cause death. The secondary endpoint was the incidence of stroke and major bleeding. The association of NOAC versus VKA treatment with these endpoints was assessed with multivariable Cox regression, using the VKA group as reference. A total of 330 octogenarian patients with AF were included with a mean (± SD) age of 83.9 ± 3.5 years. At discharge, 53.3% received a NOAC, 30% a VKA, and 16.7% no OAC. Patients on OAC were followed-up over a median of 2.6-years . The adjusted risk of all-cause death was not different in the NOAC group, compared with the VKA group (hazard ratio [HR], 0.72; 95% confidence intervals [CI] 0.50-1.03; P = 0.07). The risk of stroke or major bleeding was not different either (all P > 0.05). In conclusion, in this cohort of post-discharge octogenarian patients with AF, the risk for all-cause death was similar in NOAC versus VKA users, after adjustment for baseline covariates. No differences in stroke and major bleeding events among these treatment groups were revealed.
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Affiliation(s)
- Anastasios Papanastasiou
- First Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Anastasios Kartas
- First Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Athanasios Samaras
- First Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Eleni Vrana
- First Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Andreas Papazoglou
- First Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Dimitrios V Moysidis
- First Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Amalia Baroutidou
- First Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Michail Botis
- First Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Evaggelos Liampas
- First Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Ioannis Vouloagkas
- First Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Evangelia Mareti
- 2nd Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Efstratios Karagiannidis
- First Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Haralambos Karvounis
- First Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Apostolos Tzikas
- First Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece.,Interbalkan European Medical Center, Asklipiou 10, Pylaia, Thessaloniki, Greece
| | - George Giannakoulas
- First Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece.
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16
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Didagelos M, McEntegart M, Kouparanis A, Tsigkas G, Koutouzis M, Tsiafoutis I, Kassimis G, Oldroyd KG, Ziakas A. Distal Transradial (Snuffbox) Access for Coronary Catheterization: A Systematic Review. Cardiol Rev 2021; 29:210-216. [PMID: 34061817 DOI: 10.1097/crd.0000000000000339] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Distal transradial access, through puncture of the radial artery at its course in the anatomical snuffbox, has emerged recently as an alternative approach for coronary catheterization. Several advantages of this approach seem promising and several studies are trying to elucidate its features. This review provides an overview of the snuffbox approach for coronary catheterization and summarizes the key results of the research conducted so far.
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Affiliation(s)
- Matthaios Didagelos
- From the Interventional Cardiology Department, West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank, UK
- 1st Cardiology Department, AHEPA University General Hospital, Aristotle University of Thessaloniki, Greece
| | - Margaret McEntegart
- From the Interventional Cardiology Department, West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank, UK
| | - Antonios Kouparanis
- 1st Cardiology Department, AHEPA University General Hospital, Aristotle University of Thessaloniki, Greece
| | - Grigorios Tsigkas
- Cardiology Department, School of Medicine, University of Patras, Rion, Greece
| | - Michael Koutouzis
- Cardiology Department, Hellenic Red Cross General Hospital, Athens, Greece
| | - Ioannis Tsiafoutis
- Cardiology Department, Hellenic Red Cross General Hospital, Athens, Greece
| | - Georgios Kassimis
- 2nd Cardiology Department, Hippokration Hospital, Medical School, Aristotle University of Thessaloniki, Greece
| | - Keith G Oldroyd
- From the Interventional Cardiology Department, West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank, UK
| | - Antonios Ziakas
- 1st Cardiology Department, AHEPA University General Hospital, Aristotle University of Thessaloniki, Greece
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17
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Boer CG, Szilagyi I, Nguyen NL, Neogi T, Meulenbelt I, Ikram MA, Uitterlinden AG, Bierma-Zeinstra S, Stricker BH, van Meurs JB. Vitamin K antagonist anticoagulant usage is associated with increased incidence and progression of osteoarthritis. Ann Rheum Dis 2021; 80:598-604. [PMID: 34412027 PMCID: PMC8053344 DOI: 10.1136/annrheumdis-2020-219483] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 01/19/2021] [Accepted: 01/20/2021] [Indexed: 12/15/2022]
Abstract
OBJECTIVES Vitamin K is hypothesised to play a role in osteoarthritis (OA) pathogenesis through effects on vitamin K-dependent bone and cartilage proteins, and therefore may represent a modifiable risk factor. A genetic variant in a vitamin K-dependent protein that is an essential inhibitor for cartilage calcification, matrix Gla protein (MGP), was associated with an increased risk for OA. Vitamin K antagonist anticoagulants (VKAs), such as warfarin and acenocoumarol, act as anticoagulants through inhibition of vitamin K-dependent blood coagulation proteins. VKAs likely also affect the functioning of other vitamin K-dependent proteins such as MGP. METHODS We investigated the effect of acenocoumarol usage on progression and incidence of radiographic OA in 3494 participants of the Rotterdam Study cohort. We also examined the effect of MGP and VKORC1 single nucleotide variants on this association. RESULTS Acenocoumarol usage was associated with an increased risk of OA incidence and progression (OR=2.50, 95% CI=1.94-3.20), both for knee (OR=2.34, 95% CI=1.67-3.22) and hip OA (OR=2.74, 95% CI=1.82-4.11). Among acenocoumarol users, carriers of the high VKORC1(BB) expression haplotype together with the MGP OA risk allele (rs1800801-T) had an increased risk of OA incidence and progression (OR=4.18, 95% CI=2.69-6.50), while this relationship was not present in non-users of that group (OR=1.01, 95% CI=0.78-1.33). CONCLUSIONS These findings support the importance of vitamin K and vitamin K-dependent proteins, as MGP, in the pathogenesis of OA. Additionally, these results may have direct implications for the clinical prevention of OA, supporting the consideration of direct oral anticoagulants in favour of VKAs.
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Affiliation(s)
- Cindy G Boer
- Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Ingrid Szilagyi
- Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
- Department of General Practice, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - N Long Nguyen
- Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Tuhina Neogi
- Section of Rheumatology, Department of Medicine, Boston University Medical Campus, Boston, Massachusetts, USA
| | - Ingrid Meulenbelt
- Section Molecular Epidemiology, Department Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | - M Arfan Ikram
- Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - André G Uitterlinden
- Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
- Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Sita Bierma-Zeinstra
- Department of General Practice, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Bruno H Stricker
- Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Joyce B van Meurs
- Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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18
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Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, Boriani G, Castella M, Dan GA, Dilaveris PE, Fauchier L, Filippatos G, Kalman JM, Meir ML, Lane DA, Lebeau JP, Lettino M, Lip GY, Pinto FJ, Neil Thomas G, Valgimigli M, Van Gelder IC, Van Putte BP, Watkins CL. Guía ESC 2020 sobre el diagnóstico y tratamiento de la fibrilación auricular, desarrollada en colaboración de la European Association of Cardio-Thoracic Surgery (EACTS). Rev Esp Cardiol 2021. [DOI: 10.1016/j.recesp.2020.10.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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19
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Takamoto K, Sakamoto JI, Ito S, Kimura T, Manabe E, Shikata T, Asakura M, Ishihara M, Tsujino T. Low Quality of Warfarin Therapy is Associated With Female Gender but Not With Polypharmacy in Patients With Atrial Fibrillation. Front Pharmacol 2021; 12:651799. [PMID: 33981231 PMCID: PMC8110202 DOI: 10.3389/fphar.2021.651799] [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: 01/13/2021] [Accepted: 04/12/2021] [Indexed: 11/23/2022] Open
Abstract
Background: We examined the impact of polypharmacy on the quality of the anticoagulation therapy in patients with atrial fibrillation. We also examined the factors that affect the stability of warfarin therapy. Methods and Results: This retrospective study was conducted using data from 157 consecutive outpatients with atrial fibrillation in a single tertiary referral hospital. Patients who were prescribed warfarin continuously and for whom PT-INR was examined at least three times in a year were included in this study. We examined the quality of warfarin therapy using time in the therapeutic INR range (TTR), percentage of PT-INR determinations in range (PINRR), and the coefficient variation (CV) of PT-INR. We found that the number of prescribed medicines was significantly associated with high BMI and low eGFR, but not with TTR, PINRR, and the coefficient variation of PT-INR in patients with atrial fibrillation. We also found that female gender was independently associated with low PINRR in this study population. Conclusion: Polypharmacy did not deteriorate the quality of warfarin therapy in patients with atrial fibrillation treated in the tertiary referral hospital. Female gender was an independent predictor of the low quality of warfarin therapy.
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Affiliation(s)
- Kojiro Takamoto
- Graduate School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan.,Hyogo College of Medicine Sasayama Medical Center, Sasayama, Japan
| | - Jun-Ichi Sakamoto
- Graduate School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan.,Department of Pharmacy, Hyogo College of Medicine Hospital, Nishinomiya, Japan
| | - Satoyasu Ito
- Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan
| | - Takeshi Kimura
- Department of Pharmacy, Hyogo College of Medicine Hospital, Nishinomiya, Japan
| | - Eri Manabe
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | | | - Masanori Asakura
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Masaharu Ishihara
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Takeshi Tsujino
- Graduate School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan.,Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan.,Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
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20
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Barbieri MA, Cutroneo PM, Baratelli C, Cicala G, Battaglia A, Santoro V, Andò G, Spina E. Adverse drug reactions with oral anticoagulants: data from sicilian spontaneous reporting system database. J Clin Pharm Ther 2021; 46:1027-1040. [PMID: 33646603 DOI: 10.1111/jcpt.13391] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 01/07/2021] [Accepted: 02/09/2021] [Indexed: 12/19/2022]
Abstract
OBJECTIVE Direct oral anticoagulants (DOACs) were developed to avoid the limitations of vitamin K antagonists (VKAs). DOACs are associated with a greater incidence of gastrointestinal bleeding and a smaller number of intracranial haemorrhages than VKAs. Therefore, it is important to deepen our knowledge of their safety profiles. The aim of this study was thus to analyse adverse drug reaction (ADR) reports on DOACs and VKAs using the Sicilian Spontaneous Reporting System (SRS) database. METHODS All ADR reports with DOACs and VKAs as suspected drugs that were entered into the Sicilian SRS database during the period 2001-2019 were selected. In detail, all reports with the following single active substances were included: dabigatran etexilate, rivaroxaban, apixaban and edoxaban; acenocoumarol and warfarin were included as a comparator group. Descriptive statistical methodology was used to evaluate characteristics of the reported cases with a case-by-case assessment. RESULTS AND DISCUSSION Out of 521 reports related to anticoagulants, 444 (85.2%) and 77 (14.8%) involved DOACs and VKAs, respectively. DOAC-related reports were mainly of gastrointestinal disorders. In contrast, VKAs were mostly associated with blood and lymphatic system disorders, injury, investigations and vascular disorders. Many more cases of ADRs in the form of gastrointestinal disorders concerned dabigatran etexilate (n = 179, 73.7%) than the other DOACs, while ADRs in the form of blood disorders were mainly associated with acenocoumarol (n = 27, 57.4%). The most commonly reported Preferred Terms for DOACs were dyspepsia (n = 89, 17.1%), upper abdominal pain (n = 41, 9.2%) and pruritus (n = 26, 5.8%), whereas for VKAs, they were anaemia (n = 21, 27.3%) and hypocoagulable state (n = 18, 3.5%). Potentially interacting concomitant medications particularly included antithrombotic agents (n = 19, 4.3%) for DOACs and proton-pump inhibitors (PPIs) (n = 37, 48.1%) and antithrombotic agents (n = 13, 16.9%) for VKAs. CONCLUSION The ADRs most commonly associated with DOACs, especially dabigatran, were gastrointestinal disorders, particularly gastrointestinal bleeding. Our study also highlights the potential role of drug-drug interactions in the ADRs. The cases of gastrointestinal bleeding highlight the need for careful prescribing of DOACs and use of potentially interacting concomitant drugs.
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Affiliation(s)
| | - Paola Maria Cutroneo
- Sicilian Regional Pharmacovigilance Centre, University Hospital of Messina, Messina, Italy
| | - Chiara Baratelli
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Giuseppe Cicala
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Alessandro Battaglia
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Vincenza Santoro
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Giuseppe Andò
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Edoardo Spina
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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21
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Trends in Stroke Prevention between 2014 and 2018 in Hospitalized Atrial Fibrillation Patients. Cardiol Res Pract 2021; 2021:6657776. [PMID: 33628491 PMCID: PMC7886594 DOI: 10.1155/2021/6657776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 01/08/2021] [Accepted: 01/28/2021] [Indexed: 12/02/2022] Open
Abstract
In recent years, significant changes in stroke prophylaxis in patients with atrial fibrillation (AF) have been observed. Non-vitamin K antagonist oral anticoagulants (NOACs) are more commonly used in the prevention of thromboembolic complications in patients with AF. The aim of the study was to evaluate recommended stroke prophylaxis in patients with AF and to identify predictors of using NOACs in patients treated with anticoagulant therapy. The present study was a retrospective, observational, single-center study which included consecutively hospitalized patients in the reference cardiology center from January 2014 to December 2018. In the study group of 4027 patients with AF, to prevent thromboembolic complications, OACs were used in 3680 patients (91.4%), an antiplatelet drug(s) was used in 124 patients (3.1%), and 223 patients (5.5%) did not undergo any thromboembolic event prevention. In the group of 3680 patients treated with OACs, 2311 patients (62.8%) received NOACs and 1639 patients (37.2%), VKAs. Independent predictors of the use of NOACs were age (OR, 1.02; 95% CI, 1.01–1.03; P < 0.001), a previous thromboembolic event (OR, 1.29; 95% CI, 1.01–1.65; P=0.04), nonpermanent AF (OR, 1.61; 95% CI, 1.34–1.93; P < 0.001), and eGFR (OR, 1.22; 95% CI, 1.02–1.46; P=0.03). Between 2014 and 2018, an increase of patients treated with OACs, mainly with NOACs, was observed. Age, past thromboembolic complications, nonpermanent AF, and preserved renal function determined the choice of NOACs.
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22
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Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, Boriani G, Castella M, Dan GA, Dilaveris PE, Fauchier L, Filippatos G, Kalman JM, La Meir M, Lane DA, Lebeau JP, Lettino M, Lip GYH, Pinto FJ, Thomas GN, Valgimigli M, Van Gelder IC, Van Putte BP, Watkins CL. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021; 42:373-498. [PMID: 32860505 DOI: 10.1093/eurheartj/ehaa612] [Citation(s) in RCA: 6316] [Impact Index Per Article: 1579.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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23
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Shen NN, Wu Y, Wang N, Kong LC, Zhang C, Wang JL, Gu ZC, Chen J. Direct Oral Anticoagulants vs. Vitamin-K Antagonists in the Elderly With Atrial Fibrillation: A Systematic Review Comparing Benefits and Harms Between Observational Studies and Randomized Controlled Trials. Front Cardiovasc Med 2020; 7:132. [PMID: 33134323 PMCID: PMC7511536 DOI: 10.3389/fcvm.2020.00132] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 06/29/2020] [Indexed: 02/05/2023] Open
Abstract
Background: The publication of high-quality observational studies (OSs) has fueled reassessment of the treatment effects of direct oral anticoagulants (DOACs) in the elderly with atrial fibrillation (AF). Methods: The MEDLINE, EMBASE, and Cochrane Library databases were systematically searched (through July 1, 2019) for eligible OSs and randomized controlled trials (RCTs) that reported effectiveness outcomes [stroke or systemic embolism (SE)] or safety outcomes [intracranial hemorrhage (ICH), major bleeding, gastrointestinal bleeding (GIB), myocardial infarction (MI), and all-cause mortality] for DOACs and vitamin-K antagonists (VKAs) in elderly AF patients. A random-effects model was applied to calculate adjusted hazard ratios (HRs) for OSs and relative risks (RRs) for RCTs. Interaction analyses and the ratio of HR (RHR) were used to assess and compare OSs and RCTs. Results: A total of 32 studies involving 547,419 patients were included. No significant difference in treatment effect estimates was found between 27 OSs and 5 RCTs [P interaction > 0.05 for each and all 95% confidence interval (CI) of RHR crossed 1.0]. Compared with VKAs, DOACs significantly reduced risk for stroke/SE (OSs, HR: 0.87, 95% CI: 0.81-0.94; RCT, RR: 0.82, 95% CI: 0.67-0.96), and ICH (OSs: 0.47 [0.37-0.57]; RCTs: 0.47 [0.31-0.63]), without increasing risk for GIB (OSs: 1.21 [0.98-1.43]; RCTs: 1.34 [0.91-1.77]), and all-cause mortality (OSs: 1.01 [0.92-1.11]; RCTs: 0.94 [0.87-1.00]). Among OSs, DOACs significantly decreased risk for major bleeding (0.87 [0.77-0.98]) and MI (0.89 [0.79-0.99]). It was found that dabigatran, but not other DOACs, significantly increased risk for GIB (1.48 [1.23-1.72]). Conclusions: DOACs were demonstrated to be more effective and safer than VKAs in elderly AF patients, whereas dabigatran users had a 48% increase in risk for GIB.
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Affiliation(s)
- Nan-Nan Shen
- Department of Pharmacy, Affiliated Hospital of Shaoxing University, Shaoxing, China.,Department of Pharmacy, Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yue Wu
- Department of Pharmacy, Renmin Hospital, Wuhan University, Wuhan, China
| | - Na Wang
- Department of Pharmacy, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ling-Cong Kong
- Department of Pharmacy, Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chi Zhang
- Department of Pharmacy, Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jia-Liang Wang
- Department of Pharmacy, Affiliated Hospital of Shaoxing University, Shaoxing, China
| | - Zhi-Chun Gu
- Department of Pharmacy, Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jin Chen
- Department of Evidence-Based Medicine and Clinical Epidemiology, West China Hospital, Sichuan University, Chengdu, China
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24
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Grymonprez M, Steurbaut S, De Backer TL, Petrovic M, Lahousse L. Effectiveness and Safety of Oral Anticoagulants in Older Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis. Front Pharmacol 2020; 11:583311. [PMID: 33013422 PMCID: PMC7509201 DOI: 10.3389/fphar.2020.583311] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 08/20/2020] [Indexed: 12/17/2022] Open
Abstract
Background and Objective Atrial fibrillation (AF), the most common cardiac arrhythmia, typically increases with age. Oral anticoagulants (OACs) are the cornerstone of treatment to reduce the associated risk for systemic thromboembolism. Four large randomized controlled trials (RCTs) have shown that non-vitamin K antagonist oral anticoagulants (NOACs) are non-inferior to vitamin K antagonists (VKAs) in preventing stroke and systemic embolism, as well as regarding their risk for major bleeding. However, as vulnerable geriatric patients with AF were largely underrepresented in these trials, physicians are faced with the challenge of choosing the right anticoagulant for geriatric patients in real-life clinical practice. In this vulnerable patient group, NOACs tend to be underused or underdosed due to concerns of excessive fall-related intracranial bleeding, cognitive impairment, multiple drug-drug interactions, low body weight or impaired renal function. As life expectancy continues to rise worldwide, the number of geriatric patients substantially increases. Therefore, there is an urgent need for a critical appraisal of the added value of NOACs in geriatric patients with AF at high thromboembolic and bleeding risk. Methods and Results This systematic review provides an overview of the literature on the impact of increased age (≥75 years), multimorbidity, polypharmacy, increased falling risk, frailty and dementia on the effectiveness and safety of NOACs as compared to VKAs, after searching the Medline database. Moreover, a meta-analysis on the impact of increased age ≥75 years old was performed after pooling results from 6 post hoc analyses of RCTs and 6 longitudinal observational cohort studies, highlighting the superior effectiveness (hazard ratio (HR) 0.83, 95% confidence interval (CI) [0.74–0.94] for stroke/SE; HR 0.77, 95%CI [0.65–0.92] for mortality) and non-inferior safety (HR 0.93, 95%CI [0.86–1.01] for major bleeding; HR 0.58, 95%CI [0.50–0.67] for intracranial bleeding; HR 1.17, 95%CI [0.99–1.38] for gastrointestinal bleeding) of NOACs versus VKAs in older AF patients. Conclusion Across geriatric subgroups, apixaban was consistently associated with the most favourable benefit-risk profile and should therefore be preferred in geriatric patients with AF. However, research gaps on the impact of increased falling risk, frailty and baseline dementia were identified, requiring careful consideration while awaiting more results.
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Affiliation(s)
- Maxim Grymonprez
- Pharmaceutical Care Unit, Department of Bioanalysis, Ghent University, Ghent, Belgium
| | - Stephane Steurbaut
- Centre for Pharmaceutical Research, Vrije Universiteit Brussel, Jette, Belgium
| | - Tine L De Backer
- Department of Cardiology, Ghent University Hospital, Ghent, Belgium
| | - Mirko Petrovic
- Department of Geriatrics, Ghent University Hospital, Ghent, Belgium
| | - Lies Lahousse
- Pharmaceutical Care Unit, Department of Bioanalysis, Ghent University, Ghent, Belgium.,Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands
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25
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Diener HC, Landmesser U. Percutaneous left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation. FUTURE NEUROLOGY 2020. [DOI: 10.2217/fnl-2020-0001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Patients with atrial fibrillation (AF) have a fivefold higher risk of stroke than persons in sinus rhythm. Effective stroke prevention is achieved with oral anticoagulants such as vitamin K antagonists or nonvitamin K oral anticoagulants. An alternative for stroke prevention in patients with AF is the closure of the left atrial appendage (LAA) with a percutaneously applied closure system. The two large randomized studies PROTECT-AF and PREVAIL failed to show superiority of LAA closure over anticoagulation in patients with AF. Meta-analyses of studies and registries, however, suggest that LAA closure has particular advantages with regard to the reduction of severe bleeding complications. Currently, several prospective randomized studies are being conducted in different patient populations to evaluate the benefit of LAA closure in comparison to standard of care. Currently, LAA closure is recommended in patients after intracranial hemorrhage, with advanced renal failure, after severe gastrointestinal bleeding, in patients with a high risk of recurrent ischemic stroke and elderly patients with high risk of bleeding and falling.
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Affiliation(s)
- Hans-Christoph Diener
- Institute for Medical Informatics, Biometry & Epidemiology, Medical Faculty, University Duisburg-Essen, Essen, Germany
| | - Ulf Landmesser
- Department of Cardiology, Campus Benjamin Franklin (CBF), Charité – Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute of Health (BIH), German Center of Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany
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26
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Anticoagulation decisions in elderly patients with stroke. Rev Neurol (Paris) 2020; 176:692-700. [PMID: 32631675 DOI: 10.1016/j.neurol.2020.04.015] [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: 01/06/2020] [Revised: 04/27/2020] [Accepted: 04/29/2020] [Indexed: 11/22/2022]
Abstract
Primary and secondary prevention of stroke is often a challenge in elderly patients due to the increase in both thrombotic and hemorrhagic risks with age. In some cases, there is sufficient data in the elderly population to allow recommendations or anticoagulation decisions to be made, such as for the indication of anticoagulation to prevent stroke related to atrial fibrillation (AF) or the choice of oral anticoagulant therapy in this situation. In other situations, the less robust data leave some questions; this is the case for the delay to initiate an oral anticoagulant therapy after an AF-related ischemic stroke, for the management of antithrombotic treatment after a stroke of undetermined cause or after intracranial bleeding or in a high-risk bleeding situation associated with stroke in the elderly subject. These issues will be discussed in this paper.
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Nyamu DG, Guantai AN, Osanjo GO, Godman B, Aklillu E. Profiles of patients on warfarin anticoagulation therapy in a leading tertiary referral hospital in Kenya; findings and implications for Kenya. Expert Rev Cardiovasc Ther 2020; 18:165-173. [DOI: 10.1080/14779072.2020.1734452] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Affiliation(s)
- David Gitonga Nyamu
- Department of Pharmaceutics & Pharmacy Practice, School of Pharmacy, University of Nairobi, Nairobi, Kenya
| | - Anastasia Nkatha Guantai
- Department of Pharmacology & Pharmacognosy, School of Pharmacy, University of Nairobi, Nairobi, Kenya
| | - George Oyamo Osanjo
- Department of Pharmacology & Pharmacognosy, School of Pharmacy, University of Nairobi, Nairobi, Kenya
| | - Brian Godman
- Division of Clinical Pharmacology, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
- Department of Pharmacy, Faculty of Health Sciences, Sefako Makgatho Health Sciences University, Pretoria, South Africa
| | - Eleni Aklillu
- Division of Clinical Pharmacology, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
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Wang N, Shen NN, Wu Y, Zhang C, Pan MM, Qian Y, Gu ZC. Comparison of effectiveness and safety of direct oral anticoagulants versus vitamin-k antagonists in elderly patients with atrial fibrillation: a systematic review and cost-effectiveness analysis protocol. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:391. [PMID: 32355835 PMCID: PMC7186719 DOI: 10.21037/atm.2020.02.109] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Background Current evidence regarding the effectiveness and safety of direct oral anticoagulants (DOACs) in the elderly with atrial fibrillation (AF) remains scarce. Based on the emerging evidence from real-world studies (RWSs) associated with DOACs, we will perform a systematic review and meta-analysis of data from RWSs and randomized controlled trials (RCTs) to compare the effectiveness, safety and cost of DOACs versus Vitamin K antagonists (VKAs) in elderly patients with AF. Methods The MEDLINE, EMBASE and Cochrane Library databases will be systematically searched until June 30, 2019 for eligible RWSs and RCTs that reported the clinical outcomes between DOACs and VKAs in elderly patients with AF. The effectiveness outcome is stroke or systemic embolism (SE), and the safety outcomes are major bleeding, intracranial haemorrhage (ICH), gastrointestinal bleeding (GIB), myocardial infarction (MI) and all-cause mortality. A random-effects model will be used to calculate adjusted hazard ratios (HRs) for RWSs and relative risks (RRs) for RCTs, separately. The interaction analysis and the ratio of HRs (RHRs) will be applied to compare the treatment effect difference between RWSs and RCTs. A Markov model will be constructed to evaluate the cost-effectiveness of DOACs versus VKAs in elderly AF patients in real-world setting. Discussion This study will summarize all available evidences from RWSs and RCTs for a comprehensive and rigorous systematic review on the effectiveness and safety associated with DOACs, as well as perform a cost-effectiveness analysis to evaluate the price performance of DOACs among elderly AF patients in real clinical setting. Trial registration PROSPERO register platform (CRD42019142881, www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID =142881).
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Affiliation(s)
- Na Wang
- Department of Pharmacy, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.,Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Nan-Nan Shen
- Department of Pharmacy, Affiliated Hospital of Shaoxing University, Shaoxing 312000, China
| | - Yue Wu
- Department of Pharmacy, Wuhan University, Renmin Hospital, Wuhan 430060, China
| | - Chi Zhang
- Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Mang-Mang Pan
- Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Yan Qian
- Department of Pharmacy, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Zhi-Chun Gu
- Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
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Comparative clinical outcomes between direct oral anticoagulants and warfarin among elderly patients with non-valvular atrial fibrillation in the CMS medicare population. J Thromb Thrombolysis 2020; 48:240-249. [PMID: 30924051 PMCID: PMC6599494 DOI: 10.1007/s11239-019-01838-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Atrial fibrillation (AF) prevalence increases with age; > 80% of US adults with AF are aged ≥ 65 years. Compare the risk of stroke/systemic embolism (SE), major bleeding (MB), net clinical outcome (NCO), and major adverse cardiac events (MACE) among elderly non-valvular AF (NVAF) Medicare patients prescribed direct oral anticoagulants (DOACs) vs warfarin. NVAF patients aged ≥ 65 years who initiated DOACs (apixaban, dabigatran, and rivaroxaban) or warfarin were selected from 01JAN2013-31DEC2015 in CMS Medicare data. Propensity score matching was used to balance DOAC and warfarin cohorts. Cox proportional hazards models estimated the risk of stroke/SE, MB, NCO, and MACE. 37,525 apixaban–warfarin, 18,131 dabigatran–warfarin, and 55,359 rivaroxaban–warfarin pairs were included. Compared to warfarin, apixaban (HR: 0.69; 95% CI 0.59–0.81) and rivaroxaban (HR: 0.82; 95% CI 0.73–0.91) had lower risk of stroke/SE, and dabigatran (HR: 0.88; 95% CI 0.72–1.07) had similar risk of stroke/SE. Apixaban (MB: HR: 0.61; 95% CI 0.57–0.67; NCO: HR: 0.64; 95% CI 0.60–0.69) and dabigatran (MB: HR: 0.79; 95% CI 0.71–0.89; NCO: HR: 0.84; 95% CI 0.76–0.93) had lower risk of MB and NCO, and rivaroxaban had higher risk of MB (HR: 1.08; 95% CI 1.02–1.14) and similar risk of NCO (HR: 1.04; 95% CI 0.99–1.09). Compared to warfarin, apixaban had a lower risk for stroke/SE, MB, and NCO; dabigatran had a lower risk of MB and NCO; and rivaroxaban had a lower risk of stroke/SE but higher risk of MB. All DOACs had lower risk of MACE compared to warfarin.
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Silverio A, Di Maio M, Prota C, De Angelis E, Radano I, Citro R, Carrizzo A, Ciccarelli M, Vecchione C, Capodanno D, Galasso G. Safety and efficacy of non-vitamin K antagonist oral anticoagulants in elderly patients with atrial fibrillation: systematic review and meta-analysis of 22 studies and 440 281 patients. EUROPEAN HEART JOURNAL. CARDIOVASCULAR PHARMACOTHERAPY 2019; 7:f20-f29. [PMID: 31830264 DOI: 10.1093/ehjcvp/pvz073] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Revised: 10/27/2019] [Accepted: 12/10/2019] [Indexed: 12/31/2022]
Abstract
AIMS The aim of the present meta-analysis was to evaluate the efficacy and safety of non-vitamin K oral antagonists (NOACs) vs. vitamin K antagonists (VKAs) in elderly patients with atrial fibrillation (AF) and indirectly compare NOACs in this population. METHODS AND RESULTS MEDLINE, Cochrane, ISI Web of Sciences, and SCOPUS were searched for randomized or adjusted observational studies comparing NOACs vs. VKAs for stroke prevention in AF patients ≥75 years. The primary efficacy and safety outcomes of this meta-analysis were the composite of stroke and systemic embolism (SSE) and major bleedings, respectively. Other secondary outcomes were also analysed. The analysis included 22 studies enrolling 440 281 AF patients ≥ 75 years. The risk of SSE was significantly lower with NOACs vs. VKAs [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.70-0.89], whereas no differences were found for major bleedings (HR 0.94; 95% CI 0.85-1.05). NOACs reduced the risk of intracranial bleeding (HR 0.46; 95% CI 0.38-0.58), haemorrhagic stroke (HR 0.61; 95% CI 0.48-0.79) and fatal bleeding (HR 0.46; 95% CI 0.30-0.72) but increased gastrointestinal (GI) bleedings (HR 1.46; 95% CI 1.30-1.65), compared to VKAs. The adjusted indirect comparison showed no significant differences in term of SSE between NOAC agents. Conversely, the risk of major bleeding was higher for rivaroxaban vs. apixaban (HR 1.69; 95% CI 1.39-2.08) and edoxaban (HR 1.37; 95% CI 1.14-1.67), and for dabigatran vs. apixaban (HR 1.47; 95% CI 1.18-1.85). CONCLUSION In elderly patients with AF, NOACs are associated to a lower risk of SSE, intracranial bleeding, haemorrhagic stroke and fatal bleeding than VKAs, but increase GI bleedings. In this analysis, the safety profile of individual NOAC agents was significantly different.
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Affiliation(s)
- Angelo Silverio
- Cardiology Unit, Cardiovascular and Thoracic Department, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Largo Città di Ippocrate, Salerno 84131, Italy
| | - Marco Di Maio
- Division of Cardiology, Department of Cardiothoracic and Respiratory Sciences, University of Campania "Luigi Vanvitelli", Monaldi Hospital, A.O.R.N. "Ospedali dei Colli", Naples 80131, Italy
| | - Costantina Prota
- Cardiology Unit, Cardiovascular and Thoracic Department, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Largo Città di Ippocrate, Salerno 84131, Italy
| | - Elena De Angelis
- Cardiology Unit, Cardiovascular and Thoracic Department, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Largo Città di Ippocrate, Salerno 84131, Italy
| | - Ilaria Radano
- Cardiology Unit, Cardiovascular and Thoracic Department, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Largo Città di Ippocrate, Salerno 84131, Italy
| | - Rodolfo Citro
- Cardiology Unit, Cardiovascular and Thoracic Department, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Largo Città di Ippocrate, Salerno 84131, Italy
| | - Albino Carrizzo
- Vascular Pathophysiology Unit, IRCCS Neuromed, Pozzilli, Isernia 86077, Italy
| | - Michele Ciccarelli
- Cardiology Unit, Cardiovascular and Thoracic Department, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Largo Città di Ippocrate, Salerno 84131, Italy
| | - Carmine Vecchione
- Cardiology Unit, Cardiovascular and Thoracic Department, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Largo Città di Ippocrate, Salerno 84131, Italy.,Vascular Pathophysiology Unit, IRCCS Neuromed, Pozzilli, Isernia 86077, Italy
| | - Davide Capodanno
- Division of Cardiology, AOU Policlinico-Vittorio Emanuele, Catania 95100, Italy
| | - Gennaro Galasso
- Cardiology Unit, Cardiovascular and Thoracic Department, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Largo Città di Ippocrate, Salerno 84131, Italy
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Matsumi H, Nakamura K, Eguchi E, Miyoshi T, Nakagawa K, Nishii N, Watanabe A, Ueoka A, Yoshida M, Tokunaga N, Amioka N, Yamada N, Saito D, Morita H, Ogino K, Ito H. Low Consultation Rate of General Population with Atrial Fibrillation. Int Heart J 2019; 60:1303-1307. [PMID: 31735770 DOI: 10.1536/ihj.19-062] [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: 11/18/2022]
Abstract
In order to prevent ischemic stroke, it is important to identify and treat patients with atrial fibrillation (AF) who do not consult a doctor in a medical institution. The aim of this study was to determine the consultation rate at medical institutions for patients with AF in group medical examinations conducted in a city in western Japan. Of 6101 examinees of group medical examinations (40 years of age or older) conducted in Ibara City, Okayama Prefecture, Japan, from 2012 to 2014, 4338 participants (71.1%) who were evaluated by electrocardiogram (ECG) gave written informed consent and responded to surveys in the form of questionnaires through a personal interview conducted by nurses were included in the Ibara-AF study. A cumulative total of 82 subjects were diagnosed as having AF by ECG (prevalence of AF = 1.89%), and 51 individuals had AF during the three-year period.15 (29.4%) of the 51 patients with AF did not regularly visit medical institutions. Among them, 46.7% (n = 7) and 53.3% (n = 8) of the patients were symptomatic and asymptomatic, respectively, and 73.3% of the patients had a CHADS2 score of more than one point. There were no significant differences in patients' characteristics between regular and non-regular visit groups. In conclusion, about one-third of the patients with AF did not regularly see a doctor in a medical institution and most of them had a CHADS2 score of more than one point in a Japanese rural area. Educating the public about the risks of AF is required.
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Affiliation(s)
- Hiroaki Matsumi
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
| | - Kazufumi Nakamura
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
| | - Eri Eguchi
- Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.,Department of Epidemiology, Fukushima Medical University School of Medicine
| | - Toru Miyoshi
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
| | - Koji Nakagawa
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
| | - Nobuhiro Nishii
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.,Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
| | - Atsuyuki Watanabe
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
| | - Akira Ueoka
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
| | - Masashi Yoshida
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
| | - Naoto Tokunaga
- Department of Cardiovascular Medicine, Ibara City Hospital
| | - Naofumi Amioka
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.,Department of Cardiovascular Medicine, Ibara City Hospital
| | | | - Daiji Saito
- Department of Cardiovascular Medicine, Ibara City Hospital
| | - Hiroshi Morita
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.,Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
| | - Keiki Ogino
- Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
| | - Hiroshi Ito
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Mortality risk in atrial fibrillation: the role of aspirin, vitamin K and non-vitamin K antagonists. Int J Clin Pharm 2019; 41:1536-1544. [PMID: 31595448 DOI: 10.1007/s11096-019-00916-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2018] [Accepted: 09/24/2019] [Indexed: 10/25/2022]
Abstract
Background As an alternative to vitamin K antagonist and low-dose aspirin (< 325 mg), non-vitamin K oral anticoagulants are available for the prevention of stroke in patients with atrial fibrillation. However, the mortality risk associated with these drugs in daily practice remains unclear. Objective To evaluate the risk of all-cause mortality associated with non-Vitamin K antagonist oral anticoagulants, vitamin K antagonists or aspirin in patients with atrial fibrillation. Setting A cohort study conducted among atrial fibrillation patients using the UK Clinical Practice Research Datalink (March 2008-October 2014). Method New users of vitamin K antagonists, non vitamin K oral anticoagulants, low-dose aspirin, or combination therapy were followed from the date of first prescription to the date of death, as recorded in the UK datalink. Cox proportional hazard models estimated the hazard ratio (HR) of all-cause mortality for users of NOACs, aspirin, or combination use, as compared to vitamin K antagonist. Analyses were adjusted for confounders. Main outcome measure All-cause mortality. Results We identified 31,497 patients. Non vitamin K antocoagulant use (adjusted HR [aHR] = 1.42; 95% Confidence Interval [CI] 1.18-1.71) and aspirin use (aHR = 1.64; 95% CI 1.57-1.77) were both significantly associated with a higher mortality risk than use of vitamin K antagonists. The higher mortality risk for the non vitamin K anticoagulant use was observed in men (aHR = 1.72; 95% CI 1.25-2.36), but not in women (aHR = 1.28; 95% CI 0.92-1.79. Compared to vitamin K antagonists, mortality risk associated with the non vitamin K anticoagulants and aspirin use was significantly increased in patients with higher stroke risk (CHA2DS2-VASc > 2). Conclusion Non vitamin K oral anticoagulants are associated with a higher risk on all-cause mortality, particularly in men and in patients with higher stroke risk.
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Kim Y, Hyun DY, Cho KH, Kim MC, Sim DS, Hong YJ, Kim JH, Ahn Y, Jeong MH. Snuffbox Approach for Coronary Chronic Total Occlusion Intervention Using a 7-French Sheath. Chonnam Med J 2019; 55:175-176. [PMID: 31598479 PMCID: PMC6769239 DOI: 10.4068/cmj.2019.55.3.175] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 07/16/2019] [Accepted: 08/22/2019] [Indexed: 11/30/2022] Open
Affiliation(s)
- Yongcheol Kim
- Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
| | - Dae Yong Hyun
- Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
| | - Kyung Hoon Cho
- Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
| | - Min Chul Kim
- Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
| | - Doo Sun Sim
- Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
| | - Young Joon Hong
- Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
| | - Ju Han Kim
- Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
| | - Youngkeun Ahn
- Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
| | - Myung Ho Jeong
- Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
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Wojszel ZB, Kasiukiewicz A. Determinants of anticoagulant therapy in atrial fibrillation at discharge from a geriatric ward: cross sectional study. J Thromb Thrombolysis 2019; 49:18-26. [PMID: 31471772 PMCID: PMC6954132 DOI: 10.1007/s11239-019-01937-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Oral anticoagulants (OACs) are effective in preventing stroke in older people with atrial fibrillation (AF), but they are often underused in this particularly high-risk population. The aim of the study was to identify health and functional determinants of oral anticoagulant therapy (OA) in AF at discharge from a geriatric sub-acute ward. A cross-sectional study was conducted and patients who presented with atrial fibrillation were analyzed. They were interviewed, examined, assessed with comprehensive geriatric assessment protocol, and had their hospital records analyzed. Relative risks for OA were counted and multivariable logistic regression model was built. 95 patients took part in the study (22.8% of 416 consecutively admitted to the department, 31.9% men, 73.7% 80 + year-old). 25.8% of them were on antiplatelet drugs and 58.9% on OACs. The percentage on OACs increased significantly to 73.7% at discharge (p = 0.004), mainly due to the new OACs prescription (from 11.8 to 33.3%; p < 0.001). Severe frailty (7 point Clinical Frailty Scale ≥ 6) and anemia presence, but not the risk of bleeding according to the HAS-BLED score, significantly decreased the probability of OACs prescription at discharge. There was also a trend for an association of OACs prescription with the higher total score of CHA2DS2-VASc scale. We conclude that in the real-life population of patients with AF comprehensive geriatric assessment might allow to increase significantly the number of patients on OACs, but it is limited by patient’s frailty status and anemia diagnosis.
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Affiliation(s)
- Z B Wojszel
- Department of Geriatrics, Medical University of Bialystok, Fabryczna Str. 27, 15-471, Bialystok, Poland. .,Department of Geriatrics, Hospital of the Ministry of Interior in Bialystok, Bialystok, Poland.
| | - A Kasiukiewicz
- Department of Geriatrics, Medical University of Bialystok, Fabryczna Str. 27, 15-471, Bialystok, Poland.,Department of Geriatrics, Hospital of the Ministry of Interior in Bialystok, Bialystok, Poland
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Zathar Z, Karunatilleke A, Fawzy AM, Lip GYH. Atrial Fibrillation in Older People: Concepts and Controversies. Front Med (Lausanne) 2019; 6:175. [PMID: 31440508 PMCID: PMC6694766 DOI: 10.3389/fmed.2019.00175] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 07/19/2019] [Indexed: 12/18/2022] Open
Abstract
Atrial fibrillation (AF) is the commonest cardiac rhythm abnormality and has a significant disease burden. Amongst its devastating complications is stroke, the risk of which increases with age. The stroke risk in an older person with AF is therefore tremendous, and oral-anticoagulation (OAC) therapy is central to minimizing this risk. The presence of age-associated factors such as frailty and multi-morbidities add complexity to OAC prescription decisions in older patients and often, OAC is needlessly withheld from them despite a lack of evidence to support this practice. Generally, this is driven by an over-estimation of the bleeding risk. This review article provides an overview of the concepts and controversies in managing AF in older people, with respect to the existing evidence and current practice. A literature search was conducted on Pubmed and Cochrane using keywords, and relevant articles published by the 1st of May 2019 were included. The article will shed light on common misconceptions that appear to serve as rationale for precluding OAC and focus on clinical considerations that may aid OAC prescription decisions where appropriate, to optimize AF management using an integrated, multi-disciplinary care approach. This is crucial for all patients, particularly older individuals who are most vulnerable to the deleterious consequences of this condition.
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Affiliation(s)
- Zafraan Zathar
- Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
| | - Anne Karunatilleke
- Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
| | - Ameenathul M Fawzy
- Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
| | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom.,Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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Consideration of Anticoagulation: Surgical Care for the Elderly in Current Geriatrics Reports. CURRENT GERIATRICS REPORTS 2019. [DOI: 10.1007/s13670-019-00290-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Deitelzweig S, Keshishian A, Li X, Kang A, Dhamane AD, Luo X, Balachander N, Rosenblatt L, Mardekian J, Pan X, Nadkarni A, Di Fusco M, Garcia Reeves AB, Yuce H, Lip GYH. Comparisons between Oral Anticoagulants among Older Nonvalvular Atrial Fibrillation Patients. J Am Geriatr Soc 2019; 67:1662-1671. [PMID: 31112292 PMCID: PMC6852415 DOI: 10.1111/jgs.15956] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 03/27/2019] [Accepted: 04/01/2019] [Indexed: 12/31/2022]
Abstract
OBJECTIVES Older adult patients are underrepresented in clinical trials comparing non–vitamin K antagonist oral anticoagulants (NOACs) and warfarin. This subgroup analysis of the ARISTOPHANES study used multiple data sources to compare the risk of stroke/systemic embolism (SE) and major bleeding (MB) among very old patients with nonvalvular atrial fibrillation (NVAF) prescribed NOACs or warfarin. DESIGN Retrospective observational study. SETTING The Centers for Medicare & Medicaid Services and three US commercial claims databases. PARTICIPANTS A total of 88 582 very old (aged ≥80 y) NVAF patients newly initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015. MEASUREMENTS In each database, six 1:1 propensity score matched (PSM) cohorts were created for each drug comparison. Patient cohorts were pooled from all four databases after PSM. Cox proportional hazards models were used to estimate hazard ratios (HRs) of stroke/SE and MB. RESULTS The patients in the six matched cohorts had a mean follow‐up time of 7 to 9 months. Compared with warfarin, apixaban (HR = .58; 95% confidence interval [CI] = .49‐.69), dabigatran (HR = .77; 95% CI = .60‐.99), and rivaroxaban (HR = .74; 95% CI = .65‐.85) were associated with lower risks of stroke/SE. For MB, apixaban (HR = .60; 95% CI = .54‐.67) was associated with a lower risk; dabigatran (HR = .92; 95% CI = .78‐1.07) was associated with a similar risk, and rivaroxaban (HR = 1.16; 95% CI = 1.07‐1.24) was associated with a higher risk compared with warfarin. Apixaban was associated with a lower risk of stroke/SE and MB compared with dabigatran (stroke/SE: HR = .65; 95% CI = .47‐.89; MB: HR = .60; 95% CI = .49‐.73) and rivaroxaban (stroke/SE: HR = .72; 95% CI = .59‐.86; MB: HR = .50; 95% CI = .45‐.55). Dabigatran was associated with a lower risk of MB (HR = .77; 95% CI = .67‐.90) compared with rivaroxaban. CONCLUSION Among very old NVAF patients, NOACs were associated with lower rates of stroke/SE and varying rates of MB compared with warfarin. J Am Geriatr Soc 67:1662–1671, 2019
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Affiliation(s)
- Steven Deitelzweig
- Department of Hospital Medicine, Ochsner Clinic Foundation, New Orleans, Louisiana.,Ochsner Clinical School, The University of Queensland School of Medicine, New Orleans, Louisiana
| | - Allison Keshishian
- STATinMED Research, Ann Arbor, Michigan.,New York City College of Technology, City University of New York, New York, New York
| | - Xiaoyan Li
- Bristol-Myers Squibb Company, Lawrenceville, New Jersey
| | - Amiee Kang
- Bristol-Myers Squibb Company, Lawrenceville, New Jersey
| | | | | | | | | | | | - Xianying Pan
- Bristol-Myers Squibb Company, Lawrenceville, New Jersey
| | | | | | - Alessandra B Garcia Reeves
- Bristol-Myers Squibb Company, Lawrenceville, New Jersey.,University of North Carolina, Chapel Hill, North Carolina
| | - Huseyin Yuce
- New York City College of Technology, City University of New York, New York, New York
| | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom.,Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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Effectiveness and Safety of Direct Oral Anticoagulants versus Vitamin K Antagonists for People Aged 75 Years and over with Atrial Fibrillation: A Systematic Review and Meta-Analyses of Observational Studies. J Clin Med 2019; 8:jcm8040554. [PMID: 31022899 PMCID: PMC6518135 DOI: 10.3390/jcm8040554] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Revised: 04/18/2019] [Accepted: 04/18/2019] [Indexed: 11/22/2022] Open
Abstract
Older people, are underrepresented in randomised controlled trials of direct oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation (AF). The aim of this study was to combine data from observational studies to provide evidence for the treatment of people aged ≥75 years. Medline, Embase, Scopus and Web of Science were searched. The primary effectiveness outcome was ischaemic stroke. Safety outcomes were major bleeding, intracranial haemorrhage, gastrointestinal bleeding, myocardial infarction, and mortality. Twenty-two studies were eligible for inclusion. Two studies related specifically to people ≥75 years but were excluded from meta-analysis due to low quality; all data in the meta-analyses were from subgroups. The pooled risk estimate of ischaemic stroke was slightly lower for DOACs. There was no significant difference in major bleeding, mortality, or myocardial infarction. Risk of intracranial haemorrhage was 44% lower with DOACs, but risk of GI bleeding was 46% higher. Our results suggest that DOACs may be preferable for the majority of older patients with AF, provided they are not at significant risk of a GI bleed. However, these results are based entirely on data from subgroup analyses so should be interpreted cautiously. There is a need for adequately powered research in this patient group.
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Monelli M, Molteni M, Cassetti G, Bagnara L, De Grazia V, Zingale L, Zilli F, Bussotti M, Totaro P, De Maria B, Dalla Vecchia LA. Non-vitamin K oral anticoagulant use in the elderly: a prospective real-world study - data from the REGIstry of patients on Non-vitamin K oral Anticoagulants (REGINA). Vasc Health Risk Manag 2019; 15:19-25. [PMID: 30833810 PMCID: PMC6378887 DOI: 10.2147/vhrm.s191208] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Purpose Numerous studies on thromboembolic prevention for non-valvular atrial fibrillation (NVAF) have shown either equal or better efficacy and safety of non-vitamin K oral anticoagulants (NOACs) compared to warfarin, even for patients aged ≥75 years. Data on elderly patients, in particular, octogenarians, are lacking. Paradoxically, this population is the one with the highest risk of bleeding and stroke with a worse prognosis. This study aims to describe safety and effectiveness of NOACs in an elderly comorbid population. Patients and methods REGIstry of patients on Non-vitamin K oral Anticoagulants (REGINA) is a prospective observational study enrolling consecutive NVAF patients started on NOACs and followed up to 1 year (at 1, 6, 12 months). The primary endpoint was the incidence rate of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB). The secondary endpoints were the incidence of 1) stroke or systemic embolism, 2) hospitalization, 3) death, and 4) drug-related adverse events. Results We enrolled 227 patients aged 81.6±6.1 years (range 67–95 years; ≥80 years in 59.4%). The median CHA2DS2-VASc was 5 (IQR 4–5) and HAS-BLED was 4 (IQR 3–5). The estimated glomerular filtration rate was 59.27±24.12 mL/min. During follow-up, only 10 MB and 23 CRNMB occurred, with a total incidence of 4.4% (95% CI: 1.7%–7.17%) and 5.7% (95% CI: 2.68%–8.72%), respectively. There were 2 cerebral ischemic events, with a total incidence of 0.88% (95% CI: 0.84%–0.92%), 23 NOAC-related hospitalizations, no NOAC-related deaths, and 4 minor drug-related adverse effects. Conclusion In a population of aged and clinically complex patients, mainly octogenarians, NOACs were safe and effective.
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Affiliation(s)
- Mauro Monelli
- Cardiac Rehabilitation Department, IRCCS Istituti Clinici Scientifici Maugeri, Milano, Italy,
| | - Mauro Molteni
- Cardiac Rehabilitation Department, IRCCS Istituti Clinici Scientifici Maugeri, Milano, Italy,
| | - Giuseppina Cassetti
- Cardiac Rehabilitation Department, IRCCS Istituti Clinici Scientifici Maugeri, Milano, Italy,
| | - Laura Bagnara
- Cardiac Rehabilitation Department, IRCCS Istituti Clinici Scientifici Maugeri, Milano, Italy,
| | - Valeria De Grazia
- Cardiac Rehabilitation Department, IRCCS Istituti Clinici Scientifici Maugeri, Milano, Italy,
| | - Lorenza Zingale
- Cardiac Rehabilitation Department, IRCCS Istituti Clinici Scientifici Maugeri, Milano, Italy,
| | - Franca Zilli
- Cardiac Rehabilitation Department, IRCCS Istituti Clinici Scientifici Maugeri, Milano, Italy,
| | - Maurizio Bussotti
- Cardiac Rehabilitation Department, IRCCS Istituti Clinici Scientifici Maugeri, Milano, Italy,
| | - Paolo Totaro
- Cardiac Rehabilitation Department, IRCCS Istituti Clinici Scientifici Maugeri, Milano, Italy,
| | - Beatrice De Maria
- Cardiac Rehabilitation Department, IRCCS Istituti Clinici Scientifici Maugeri, Milano, Italy,
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Kim IS, Kim HJ, Yu HT, Kim TH, Uhm JS, Kim JY, Joung B, Lee MH, Pak HN. Non-vitamin K antagonist oral anticoagulants with amiodarone, P-glycoprotein inhibitors, or polypharmacy in patients with atrial fibrillation: Systematic review and meta-analysis. J Cardiol 2019; 73:515-521. [PMID: 30770140 DOI: 10.1016/j.jjcc.2018.12.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2018] [Revised: 12/13/2018] [Accepted: 12/19/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Amiodarone, which inhibits CYP2C9 and P-glycoprotein, is commonly prescribed with non-vitamin K antagonist oral anticoagulants (NOACs) and polypharmacy in high-risk atrial fibrillation (AF) patients. We studied efficacy and safety of NOACs in AF patients receiving amiodarone, P-glycoprotein inhibitor, or polypharmacy. METHODS After a systematic database search (Medline, EMBASE, CENTRAL, SCOPUS, and Web of Science), four phase-III randomized trials comparing NOACs and warfarin in "with/without amiodarone," "with/without P-glycoprotein inhibitors," or "with/without multiple (≥5, polypharmacy) concomitant drugs" subgroups were included. The outcomes were pooled using a random-effects model to determine the relative risks (RRs) for stroke/systemic thromboembolism (SSTE), major bleeding (MB), intracranial hemorrhage (ICH), and all-cause mortality. RESULTS Among patients taking amiodarone, superiority of NOACs over warfarin in non-amiodarone users disappeared in terms of SSTE (p=0.11), MB (p=0.95), ICH (p=0.26), and mortality (p=0.32). No safety benefit (MB) of NOACs compared to warfarin was shown in patients taking P-glycoprotein inhibitors (p=0.47), but SSTE prevention was still superior with NOACs compared to warfarin in the same patient group [RR=0.78 (0.61-0.99), p=0.04, I2=11%]. In AF patients with polypharmacy, NOACs showed a lower risk of SSTE [RR=0.82 (0.71-0.96), p=0.01, I2=0%] and mortality [RR=0.91 (0.83-0.99), p=0.04, I2=0%], but not MB (p=0.81) compared to warfarin. CONCLUSIONS NOACs were equivalent to warfarin among AF patients with concomitant amiodarone use in terms of efficacy, safety, and mortality. There was no safety benefit of NOACs over warfarin in patients using polypharmacy or P-glycoprotein inhibitors. SYSTEMATIC REVIEW REGISTRATION The protocol of this meta-analysis was registered on PROSPERO under CRD42018104808 (https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42018104808).
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Affiliation(s)
- In-Soo Kim
- Yonsei University Health System, Seoul, Republic of Korea
| | - Hyun-Jung Kim
- Department of Preventive Medicine, Institute for Evidence-based Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
| | - Hee Tae Yu
- Yonsei University Health System, Seoul, Republic of Korea
| | - Tae-Hoon Kim
- Yonsei University Health System, Seoul, Republic of Korea
| | - Jae-Sun Uhm
- Yonsei University Health System, Seoul, Republic of Korea
| | - Jong-Youn Kim
- Yonsei University Health System, Seoul, Republic of Korea
| | - Boyoung Joung
- Yonsei University Health System, Seoul, Republic of Korea
| | | | - Hui-Nam Pak
- Yonsei University Health System, Seoul, Republic of Korea.
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Kim Y, Jeong MH, Kim MC, Sim DS, Hong YJ, Kim JH, Ahn Y. Successful Drug-Eluting Stent Overexpansion with Intravascular Ultrasound Guidance for Left Main Bifurcation Lesion Via Left Snuffbox Approach. Chonnam Med J 2019; 55:66-67. [PMID: 30740345 PMCID: PMC6351329 DOI: 10.4068/cmj.2019.55.1.66] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2018] [Revised: 01/08/2019] [Accepted: 01/09/2019] [Indexed: 11/22/2022] Open
Affiliation(s)
- Yongcheol Kim
- Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
| | - Myung Ho Jeong
- Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
| | - Min Chul Kim
- Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
| | - Doo Sun Sim
- Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
| | - Young Joon Hong
- Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
| | - Ju Han Kim
- Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
| | - Youngkeun Ahn
- Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
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Contemporary trend of reduced-dose non-vitamin K anticoagulants in Japanese patients with atrial fibrillation: A cross-sectional analysis of a multicenter outpatient registry. J Cardiol 2019; 73:14-21. [DOI: 10.1016/j.jjcc.2018.09.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Revised: 08/30/2018] [Accepted: 09/04/2018] [Indexed: 11/20/2022]
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Wang CL, Wu VCC, Lee CH, Kuo CF, Chen YL, Chu PH, Chen SW, Wen MS, See LC, Chang SH. Effectiveness and safety of non-vitamin-K antagonist oral anticoagulants versus warfarin in atrial fibrillation patients with thrombocytopenia. J Thromb Thrombolysis 2018; 47:512-519. [DOI: 10.1007/s11239-018-1792-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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