Comparison of Dabigatran Versus Warfarin Treatment for Prevention of New Cerebral Lesions in Valvular Atrial Fibrillation

https://doi.org/10.1016/j.amjcard.2022.03.050Get rights and content

Warfarin is the standard anticoagulation therapy for valvular atrial fibrillation (AF); however, new oral anticoagulants have emerged as an alternative. We compared the efficacy and safety of dabigatran with conventional treatment in AF associated with left-sided valvular heart disease (VHD), including mitral stenosis (MS). Patients with AF and left-sided VHD were randomly assigned to receive dabigatran or conventional treatment. The primary end point was the occurrence of clinical stroke or a new brain lesion (silent brain infarct and microbleed) on 1-year follow-up brain magnetic resonance imaging. Patients in the dabigatran group were switched from warfarin (n = 52), antiplatelets alone (n = 5), or no therapy (n = 2) to dabigatran. In the conventional group, 53 used warfarin (including 42 MS patients), and 7 used antiplatelets. No death or clinical stroke event occurred in either group during follow-up. Silent brain infarct and microbleed occurred in 20 and 2 patients in the dabigatran group and 20 and 4 patients in the conventional treatment group. The incidence rate of the primary end point did not significantly differ between groups (34% vs 40%, relative risk 0.87, 95% confidence interval 0.59 to 1.29, p = 0.491). The primary end point rate was similar between groups in 82 patients (40 in the dabigatran group and 42 in the conventional group) with MS (32% vs 34%, relative risk 0.93, 95% confidence interval: 0.57 to 1.50, p = 0.759). In conclusion, primary end point rates after treatment with dabigatran were similar to conventional treatment in patients with significant VHD and AF. New oral anticoagulants could be a reasonable alternative to warfarin in patients with AF and VHD, which should be confirmed in future large-scale studies.

Introduction

Ischemic stroke is a major complication of atrial fibrillation (AF).1 AF patients with underlying valvular heart disease (VHD) are at higher risk of ischemic stroke in population-based studies.2,3 Standard anticoagulation is, therefore, the cornerstone of managing patients with AF and VHD. The nonvitamin K antagonist oral anticoagulants (NOAC) have replaced a large portion of warfarin use given their better efficacy and safety profiles, proved in multiple randomized controlled trials.4, 5, 6, 7 However, the role of NOACs in managing valvular AF remains undetermined, particularly in AF associated with mitral stenosis (MS).8 Dabigatran etexilate is a NOAC used to treat nonvalvular AF; evidence on the efficacy and safety of dabigatran in AF patients with native VHD is lacking. In addition, excessive risk and no benefit has been observed in patients with a mechanical prosthetic valve.9 An observational study of patients with MS and AF has suggested a positive role of NOAC in these patients; however, there were no prospective data available.10 The DECISIVE (Effectiveness of Dabigatran vs Conventional Treatment for Prevention of Silent Cerebral Infarct in Aortic and Mitral Valvular Atrial Fibrillation Patients) trial was designed to assess the therapeutic impact of dabigatran in patients with AF and left-sided VHD. We hypothesized that dabigatran would be superior to conventional treatment (warfarin or aspirin) for preventing subclinical ischemic stroke and intracranial bleeding.

Section snippets

Methods

This study was a prospective, single-center, open-label, randomized controlled trial to evaluate the efficacy and safety of dabigatran compared with warfarin in patients with valvular AF. Boehringer Ingelheim (Ingelheim, Germany) partially funded the study and provided the drug; however, they had no role in data collection, analysis, interpretation, or presenting the results. The study protocol was approved by the institutional review board of our institution (2016-0869), and written informed

Results

The number of patients who were screened, randomized, and assigned to each study group is shown in Figure 1. We enrolled 120 patients between March 2017 and October 2019 and randomly assigned them at a 1:1 ratio to the dabigatran or conventional treatment groups. One patient in the dabigatran group withdrew consent immediately after randomization, resulting in 59 patients in the dabigatran group and the baseline evaluation of 119 patients. A crossover occurred in 5 patients in the dabigatran

Discussion

In this open-label, randomized trial, we found no significant difference in the primary end points between dabigatran and conventional treatment in patients with AF and significant left-sided VHD.

The pivotal randomized trial of 4 NOACs excluded patients with moderate or severe MS and prosthetic heart valves.4, 5, 6, 7 In the sub-analysis of the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, which included patients with VHD (except moderate–severe MS or mechanical

Disclosures

The authors have no conflicts of interest to declare.

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