Key result
Interacting antiarrhythmics with DOACs link to ~30% more major bleeding without reducing stroke risk.
Why the study?
Several antiarrhythmic drugs can pharmacokinetically interact with DOACs to increase DOAC levels, but the effectiveness and safety of their concomitant use in non-valvular atrial fibrillation required assessment.
Does concomitant use of DOACs and interacting antiarrhythmic drugs increase the risk of stroke and bleeding in patients with NVAF?
Cohort (n=54,078)
Yes
Does concomitant use of DOACs and interacting antiarrhythmic drugs increase the risk of stroke and bleeding in patients with NVAF?
Hazard Ratio: 1.04 (95% CI 0.88–1.21)
Concomitant use of DOACs and interacting antiarrhythmic drugs in NVAF patients increases the risk of major bleeding without affecting stroke prevention effectiveness.
May increase major bleeding risk with DOACs plus interacting antiarrhythmics in NVAF; leaves open causal confirmation in randomized trials.
Background Several antiarrhythmic drugs can interact with direct oral anticoagulants (DOACs) through pharmacokinetic mechanisms increasing DOAC levels. Our multinational cohort study assessed the effectiveness and safety of concomitant use of DOACs and interacting antiarrhythmic drugs among patients with non-valvular atrial fibrillation (NVAF). Methods We used United Kingdom’s Clinical Practice Research Datalink and Quebec administrative claims data assembling two cohorts of patients with NVAF who initiated DOACs and added-on antiarrhythmic drugs. We assessed the risk of ischemic stroke and major bleeding associated with concomitant use of DOACs and interacting antiarrhythmic drugs (amiodarone, diltiazem, dronedarone, verapamil) versus concomitant use of DOACs and non-interacting antiarrhythmic drugs (flecainide, propafenone, sotalol) using an as-treated exposure definition. Cox models yielded hazard ratios (HRs) and 95% confidence intervals (CIs) after inverse-probability-of-treatment-weighting. We pooled site-specific estimates together using random-effects models. Secondary analyses stratified by age, sex, and individual DOACs. Results Our study cohort included 54,078 NVAF patients initiating DOACs and adding-on antiarrhythmic drugs. Concomitant use of DOACs and interacting antiarrhythmic drugs versus concomitant use of DOACs and non-interacting antiarrhythmic drugs was not associated with the risk of ischemic stroke (pooled HR, 1.04; 95% CI, 0.88–1.21; I 2 = 0%) but with an increased risk of major bleeding (pooled HR, 1.30; 95% CI, 1.19–1.41; I 2 = 58%), especially among patients < 70 years (pooled HR, 1.56; 95% CI, 1.31–1.86; I 2 = 0%). There was no effect modification by sex or individual DOAC. Conclusions Concomitant use of interacting antiarrhythmic drugs does not seem to affect the effectiveness of DOACs but may increase their risk of major bleeding.
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Meinert et al. (2025) conducted a cohort in Non-valvular atrial fibrillation (n=54,078). Concomitant use of DOACs and interacting antiarrhythmic drugs vs. Concomitant use of DOACs and non-interacting antiarrhythmic drugs was evaluated on Ischemic stroke (composite of hospitalization with ischemic stroke, transient ischemic attack, or systemic embolism) (HR 1.04, 95% CI 0.88-1.21). Concomitant use of DOACs and interacting antiarrhythmic drugs did not affect ischemic stroke risk (HR 1.04) but increased major bleeding risk (HR 1.30) compared to non-interacting drugs in NVAF.
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