Comparative effectiveness and safety of oral anticoagulants in patients with atrial fibrillation using antiarrhythmic drugs: An international cohort study

Aim Our international cohort study assessed the comparative effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) among patients with non‐valvular atrial fibrillation (NVAF) using antiarrhythmic drugs. Methods Using the United Kingdom's (UK's) Clinical Practice Research Datalink Aurum and Québec claims data, we assembled two study cohorts of patients with NVAF who initiated DOACs or VKAs while on antiarrhythmic drugs (2011–2020). Using an as‐treated exposure definition, we assessed the risks of ischemic stroke and major bleeding associated with DOACs vs . VKAs. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) after propensity score‐based inverse‐probability‐of‐treatment‐weighting. Site‐specific estimates were pooled together using random‐effects models. Secondary analyses assessed effect measure modification by individual DOAC and type of antiarrhythmic drugs (interacting vs . non‐interacting). Results The study cohort included 44 435 patients with NVAF initiating DOACs (n = 29 071) or VKAs (n = 15 364) while using antiarrhythmics. Compared to VKAs, DOACs were not associated with the risk of ischemic stroke (UK: HR, 0.90; 95% CI, 0.61–1.32/ Quebec: HR, 0.85; 95% CI, 0.70–1.03/ pooled: HR, 0.86; 95% CI 0.72–1.02; I 2 = 0%) but with a decreased risk of major bleeding (UK: HR, 0.90; 95% CI, 0.75–1.08/Quebec: HR, 0.83; 95% CI, 0.76–0.91/pooled: HR 0.84; 95% CI 0.78–0.92; I 2 = 0%); the latter was more pronounced with apixaban (pooled HR, 0.71; 95% CI, 0.63–0.81; I 2 = 74%). There was no effect modification by type of antiarrhythmic drugs. Conclusions DOACs were as effective but safer than VKAs among NVAF patients treated with antiarrhythmic drugs.