Abstract 10558: Association Between Concurrent Use of Diltiazem and DOACs and Risk of Bleeding in Atrial Fibrillation Patients

Introduction: Diltiazem is a commonly used pharmacotherapy in patients with atrial fibrillation (AF) with potential for a drug-drug interaction (DDI) with direct oral anticoagulants (DOACs). We aimed to assess the risk of bleeding after co-prescription of diltiazem and DOACs among adults with AF. Methods: We conducted a population-based, nested case-control study in Ontario, Canada. The study population included all patients with AF > 66 years on a DOAC between April 1, 2011-March 31, 2018. Cases were patients admitted with major bleeding (index date). Controls were matched in a 2:1 ratio to cases. We categorized exposure to diltiazem before the index date as: a) current users (diltiazem within 7 days); b) past users (diltiazem within 8 to 90 days); and c) unexposed (no diltiazem prescription or diltiazem prescription >90 days before index date). Conditional logistic regression models were used to examine the association between bleeding and diltiazem co-prescription. Results: Among 86,679 AF patients on a DOAC, we identified 2,766 cases (3.2%) admitted with major bleeding. The median age of AF patients was 80 years (interquartile range 75-85); 48.3% were women. After multivariable adjustment, there was a significant association between major bleeding and current use of diltiazem (adjusted odds ratio (aOR) 1.37; 95% confidence interval (CI) 1.08-1.73, p<0.009) but no significant association between major bleeding and past use of diltiazem (aOR 1.19, 95% CI 0.99-1.42, p=0.06) as compared with the unexposed group (Figure). Conclusions: Among older patients with AF on a DOAC, there was 37% increased odds of current use of diltiazem in those with versus without major bleeding.