Key result
Initiation of a DOAC while taking amiodarone was associated with elevated odds of all-cause mortality (OR 2.09, 99% CI 1.37-3.18) in a case-crossover analysis, though cohort analysis showed no difference.
Why the study?
DOACs are commonly co-prescribed with amiodarone, diltiazem, or verapamil, but whether there is a clinically relevant drug interaction between them remains unclear.
Does concomitant use of DOACs with amiodarone, diltiazem, or verapamil alter the risk of bleeding or cardiovascular outcomes compared to DOACs with beta-blockers in DOAC users?
Cohort (n=397,459)
Yes
Does concomitant use of DOACs with amiodarone, diltiazem, or verapamil alter the risk of bleeding or cardiovascular outcomes compared to DOACs with beta-blockers in DOAC users?
Odds Ratio: 2.09 (95% CI 1.37–3.18)
Co-prescription of DOACs with amiodarone, diltiazem, or verapamil is not associated with an increased long-term risk of bleeding or cardiovascular events, though there may be a transiently elevated mortality risk when initiating DOACs in patients already receiving amiodarone or diltiazem.
May warrant short-term caution at DOAC-amiodarone initiation; leaves open causal interaction versus residual confounding.
BACKGROUND: Direct oral anticoagulants (DOACs) are commonly co-prescribed with amiodarone/diltiazem/verapamil, but whether there is a drug interaction between these drugs is unclear. OBJECTIVE: The purpose of this study was to investigate the risk of clinical outcomes associated with concomitant use of DOACs and amiodarone/diltiazem/verapamil. METHODS: We identified DOAC users in the Clinical Practice Research Datalink Aurum from January 1, 2011, to December 31, 2019. We used a cohort design to estimate hazard ratios for ischemic stroke, myocardial infarction, venous thromboembolism, intracranial bleeding, gastrointestinal bleeding, other bleeding, cardiovascular mortality, and all-cause mortality, comparing DOACs + amiodarone/diltiazem/verapamil users and DOACs + beta-blocker users. A case-crossover design comparing odds of exposure to different drug initiation patterns for all outcomes in hazard window vs referent window within an individual also was conducted. RESULTS: Of 397,459 DOAC users, we included 9075 co-prescribed amiodarone, 9612 co-prescribed diltiazem, and 2907 co-prescribed verapamil. There was no difference in risk of any outcomes between DOACs + amiodarone/diltiazem/verapamil users vs DOACs + beta-blocker users in the cohort design. However, in the case-crossover design, we observed an odds ratio (OR) of 2.09 (99% confidence interval [CI] 1.37-3.18) for all-cause mortality associated with initiation of a DOAC while taking amiodarone, which was greater than that observed for DOAC monotherapy (OR 1.30; 99% CI 1.25-1.35). Similar findings were observed for cardiovascular mortality and all-cause mortality respectively with diltiazem. CONCLUSION: Our study showed no evidence of higher bleeding or cardiovascular risk associated with co-prescribed DOACs and amiodarone, diltiazem, or verapamil. Elevated risks of cardiovascular and all-cause mortality were only observed during DOAC initiation when diltiazem/amiodarone were being taken.
No takes yet. Share an insight, caveat, or question.
Wong et al. (2024) conducted a cohort in Atrial fibrillation or other indications requiring DOAC therapy (n=397,459). Initiation of a DOAC while taking amiodarone (or diltiazem/verapamil) vs. DOACs + beta-blockers (cohort) or referent window (case-crossover) was evaluated on All-cause mortality (case-crossover design for DOAC initiation while taking amiodarone) (OR 2.09, 95% CI 1.37-3.18). Initiation of a DOAC while taking amiodarone was associated with elevated odds of all-cause mortality (OR 2.09, 99% CI 1.37-3.18) in a case-crossover analysis, though cohort analysis showed no difference.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: