Net clinical benefit of a reduced dose of DOACs in non-valvular atrial fibrillation: A meta-analysis of randomized trials. (January 2022)

• Record Type: Journal Article
• Authors: Thomopoulos, Costas; Ntalakouras, John; Polyzos, Dimitris; Konstantinidis, Dimitris; Palaiodimou, Lina; Tsivgoulis, Georgios; Tsioufis, Costas
• Is Part Of: Pharmacological research. Volume 175(2022)
• Publication Date: 2022-01
• Subjects: ADRIFT Assessment of Dual Antiplatelet Therapy Versus Rivaroxaban in Atrial Fibrillation Patients Treated With Left Atrial Appendage Closure -- AF Atrial Fibrillation -- ARISTOTLE Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation -- ATLAS-ACS TIMI 51 Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-TIMI 51 -- CI Confidence Interval -- COMPASS Cardiovascular Outcomes for People Using Anticoagulation Strategies -- CV Cardiovascular -- DOACs Direct Oral Anticoagulants -- ENGAGE AF-TIMI 48 Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48 -- GALILEO Global Study Comparing a Rivaroxaban-based Antithrombotic Strategy to an Antiplatelet-based Strategy after Transcatheter Aortic Valve Replacement to Optimize Clinical Outcomes -- PRISMA Preferred Reporting Items for Systematic Reviews and Meta-analyses -- RE-LY Randomized Evaluation of Long-Term Anticoagulation Therapy -- RCTs Randomized Controlled Trials -- RoB2 Revised Cochrane Risk of Bias -- ROCKET AF Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation; Warfarin -- Non-vitamin K Antagonist Oral Anticoagulant -- Direct oral anticoagulants; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2021.105902
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: Background: In standard dosing, direct Oral Anticoagulants (DOACs) are used as an alternative to warfarin to prevent ischemic stroke and systemic embolism in non-valvular Atrial Fibrillation (AF). However, randomized comprehensive evidence considering the efficacy and safety of the low-dose DOACs in the same setting is still lacking. Toward this end, we conducted a meta-analysis of randomized trials to estimate the risk/benefit ratio, in terms of net clinical benefit, by comparing a reduced dose of DOACs and warfarin. Methods: We searched three electronic databases, covering the period until end-February 2021. All-cause death, non-fatal stroke/systemic embolism, and major bleeding events, with or without the inclusion of myocardial infarction, were used to define two different net clinical benefit outcomes. In addition, we evaluated different component outcomes of net clinical benefit as secondary outcomes. Finally, risk ratios and 95% Confidence Intervals (CI) of each outcome were calculated (random-effects model). Results: In the four randomized trials included (n = 29, 779 patients), the net clinical benefit - with or without the inclusion of myocardial infarction - of low-dose DOACs, compared to warfarin, was a 12% (95% CI, 7%−16%) or a 10% (95% CI, 5%−13%) reduction of events, respectively. Compared to warfarin, the reduced dose of DOACs decreased death outcomes, major bleeding events, and hemorrhagic stroke, whereas all thrombotic outcomes were not different among the groups. Conclusions: DOACs at low dosing present a more favorable net clinical benefit profile compared to warfarin. Graphical abstract: ga1