Effectiveness and Safety of NOAC Versus Warfarin in Patients With Atrial Fibrillation and Aortic Stenosis

Abstract

Background Guideline recommendations on the use of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with aortic stenosis are based on studies including a low number of patients with aortic stenosis. The aim of this study was to estimate the effects of NOAC versus warfarin on thromboembolism and major bleeding among AF patients with aortic stenosis. Methods and Results We emulated a target trial using observational data from Danish nationwide registries between 2013 and 2018. Thromboembolism was defined as a hospital diagnosis of ischemic stroke and/or systemic embolism, and major bleeding was defined as a hospital diagnosis of intracranial bleeding, gastrointestinal bleeding, or major or clinically relevant bleeding in other anatomic sites. Treatment effect estimates were based on an intention-to-treat and per-protocol approach. A total of 3726 patients with AF and aortic stenosis claimed a prescription for either a NOAC (2357 patients) or warfarin (1369 patients) and met the eligibility criteria for the trial. During 3 years of follow-up, the adjusted hazard ratios for thromboembolism and major bleeding were 1.62 (95% CI, 1.08-2.45) and 0.73 (0.59-0.91) for NOAC compared with warfarin in the intention-to-treat analyses. Similar results were observed in the per-protocol analyses. Conclusions In this observational study, we observed a higher risk of thromboembolism but a lower risk of major bleeding for treatment with NOACs compared with warfarin in patients with AF and aortic stenosis. This observation needs confirmation in large randomized trials in these commonly encountered patients.

Keywords: atrial fibrillation; stroke; valvular heart disease.

Figure 1. Flowchart of eligible patients to emulate the target trial.

CHA₂DS₂‐VASc indicates congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, prior stroke/transient ischemic attack/systemic embolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65–74 years, sex category [female]; and NOAC, non–vitamin K antagonist oral anticoagulant.

Figure 2. Standardized survival curve free from thromboembolic events.

Thromboembolism‐free survival probability according to treatment strategy (NOAC or warfarin) for the intention‐to‐treat analysis and the per‐protocol analysis. NOAC indicates non–vitamin K antagonist oral anticoagulant.

Figure 3. Standardized survival curve free from major bleeding events.

Major bleeding‐free survival probability according to treatment strategy (NOAC or warfarin) for the intention‐to‐treat analysis and the per‐protocol analysis. NOAC indicates non–vitamin K antagonist oral anticoagulant.