LAUSR

Introduction: Amiodarone and diltiazem are commonly prescribed cardiovascular medications in atrial fibrillation (AF) patients who take direct oral anticoagulants (DOACs). They are known to have drug-drug interactions (DDIs) with DOACs, increasing serum levels of DOACs by 40-60%, and potentially increasing risk of bleeding. Objective: To evaluate frequency of use of amiodarone or diltiazem among continuous users of DOACs in AF patients and assess factors associated with their use. Methods: The study population included all AF patients with continuous DOAC use in Ontario, Canada, ≥66 years, from April 1 2017 to March 31 2018. We used linked databases housed at ICES, Ontario. DOAC fill dates and days supplied per prescription were used to determine treatment durations. A maximum gap of 30 days between prescriptions was allowed. Multivariable logistic regression models were used to identify predictors of prescribing amiodarone or diltiazem among AF patients on DOACs. Results: In total, 5390 AF patients, ≥66 years, with continuous DOAC use were identified. Amiodarone was co-prescribed in 343 (6.4%) patients and diltiazem was co-prescribed in 604 (11.2%) patients. The presence of percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) significantly increased the odds of co-prescribing amiodarone among AF DOAC patients (OR 2.52 [95% CI 1.55, 4.10], p=0.0002 and OR 5.19 [95% CI 3.46, 7.80], p= <0.0001, respectively). The presence of chronic obstructive pulmonary disease was associated with significantly increased diltiazem co-prescription among AF DOAC patients (OR 1.55 [95% CI 1.28, 1.87], p=<0.0001) when adjusted for important patient-level factors (Tables 1&2). Conclusions: Among AF patients with continuous DOAC use, the presence of PCI or CABG was associated with increased amiodarone co-prescription. Future efforts should focus on examining the risk of bleeding in these vulnerable populations exposed to major DOAC DDIs.