Use of Novel Antithrombotic Therapies for Patients With Atrial Fibrillation and Bioprosthetic Valves
Article ID: CJ-21-1029
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Article ID: CJ-21-1029
Atrial fibrillation (AF) and valvular heart disease frequently coexist and independently increase mortality.1 Surgical and transcatheter bioprosthetic valve (BPV) implantations are common, increasingly utilized treatments for valvular heart disease.2 As per the current guidelines for the treatment of valvular heart disease, replacement of bioprosthetic aortic and mitral valves is recommended in patients aged >65 years and >70 years, respectively.3 Patients with AF and BPVs require anticoagulant therapy to prevent thromboembolic events. However, the optimal anticoagulation strategy for these patients remains unclear.
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In this issue of the Journal, Amano et al4 compare the efficacy and safety of antiplatelet therapy in patients with AF and BPVs receiving anticoagulant therapy. In their study, adding single antiplatelet therapy (SAPT) to anticoagulant therapy was associated with reduced efficacy (stroke/systemic embolism events) compared with anticoagulant therapy alone. Interestingly, the cumulative incidence of major and minor bleeding events was comparable between groups. Moreover, adding SAPT to anticoagulant therapy did not affect the incidence of cardiac events during the observation period. The authors conducted an exploratory subanalysis of the BioProsthetic Valves with Atrial Fibrillation (BPV-AF) Study, which was a retrospective, multicenter observational study, conducted in Japan between March 2011 and March 2018, that enrolled 214 patients with AF and BPVs.5 That study demonstrated that vitamin K antagonists (VKAs) were the most commonly used drugs for the treatment of AF in patients with BPVs, but there was an increasing trend for the use of novel oral anticoagulants (NOACs) in real-world clinical practice in Japan.
Currently, NOACs are frequently used for the management of patients with AF at risk for stroke. However, their efficacy and safety in patients with AF and BPVs have not been formally tested in previous large-scale randomized trials of NOACs. For example, patients with AF and BPVs were excluded from the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) and the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trials. In addition, patients with BPVs and AF comprised only 31 of 18,201 patients and 131 of 21,105 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trials, respectively.6–9 Furthermore, patients who had undergone recent (<3 months) BPV implantation were excluded from both the ARISTOTLE and ENGAGE AF-TIMI 48 trials.8,9
Guimarães et al reported that in the Rivaroxaban for Valvular Heart Disease and Atrial Fibrillation (RIVER) trial, rivaroxaban was noninferior to VKAs with respect to the mean time until death and/or cardiovascular events in patients with AF and BPVs.10 In the randomized RIVER trial, a total of 1,005 patients with AF and a bioprosthetic mitral valve were enrolled. Patients were randomly assigned to once-daily rivaroxaban 20 mg or dose-adjusted VKA (target international normalized ratio, 2–3). The primary outcome was a composite of death, major bleeding or major cardiovascular events, defined as stroke, transient ischemic attack, systemic embolism, valve thrombosis, or hospitalization for heart failure at 1 year. A primary outcome event occurred at a mean of 347.5 days among patients receiving rivaroxaban vs. 340.1 days among those receiving VKAs. The restricted mean survival time was calculated to evaluate between-group differences. Patients administered VKAs experienced 7.4 more days of event-free survival compared with those assigned rivaroxaban, but the noninferiority margin was met (95% confidence interval, −1.4 to 16.3; P for noninferiority <0.001).
In clinical practice, concomitant use of SAPT (or dual antiplatelet therapy) with anticoagulant therapy may be recommended in patients with AF who are at high risk of a platelet-driven event, such as patients with a recent acute coronary syndrome or stent implantation. A subanalysis of the ENGAGE AF-TIMI 48 trial provided data on the relative efficacy and safety of combination antithrombotic therapy.11 However, there is an inherent bias in the decision to initiate SAPT with anticoagulant therapy. Moreover, additional effects of this therapy are still unclear. A summary of the scientific evidence of antithrombotic therapies in patients with AF and BPVs is presented in the Figure. Further studies with large-scale and randomized clinical trials are needed to demonstrate the effectiveness and safety of novel antithrombotic therapies.
Summary of scientific evidence of antithrombotic therapies in patients with atrial fibrillation and bioprosthetic valves. BPV, bioprosthetic valve; NOAC, novel oral anticoagulant; RCT, randomized clinical trial; SAPT, single antiplatelet therapy; VKA, vitamin K antagonists.
Dr. Kondo received lecture fees from Daiichi-Sankyo, Bayer, Abbott Medical Japan, Biotronik Japan, Boston Scientific, Japan Lifeline, and research funds from Daiichi-Sankyo. Dr. Kobayashi received lecture fees from Abbott Medical Japan, Bayer Japan, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, and scholarship funds from Takeda Pharmaceutical, Abbott Medical Japan, Terumo, Otsuka Pharmaceutical, Boehringer Ingelheim, Astellas, Daiichi-Sankyo, Win International, Japan Lifeline, and Nipro. Dr. Kobayashi is a member of Circulation Journal’s Editorial Team.
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