Abstract 205: New Onset Heart Failure and Adverse Ischemic Events Associated with Amiodarone and Dronedarone Use among Atrial Fibrillation Patients

Abstract

Background: Dronedarone is a non-iodinated form of amiodarone that may not cause some of serious adverse effects associated with amiodarone. However, it is less effective than amiodarone in maintaining normal sinus rhythm, and it does not improve success of electrical cardioversion. Additionally, dronedarone use has been associated with new onset or worsening of heart failure (HF), including a doubling of the risk of death in patients with symptomatic heart failure. We aimed to compare the incidence of newly diagnosed HF and HF hospitalizations among dronedarone and amiodarone users. Secondary outcomes of interest included rates of acute ischemic stroke (IS) and transient ischemic attack (TIA). Methods: This retrospective study utilized administrative claims data between 1/1/2007-9/30/2011 from the HealthCore Integrated Research Environment (HIRE ® ). Patients were required to have at least one claim for atrial fibrillation. Propensity score matching was employed to adjust for differences between the cohorts. Incidence rate of HF, HF hospitalizations, IS and TIA events were compared between matched cohorts using Poisson time-to-event model. Results: The cohort consisted of 6,013 amiodarone and 1,534 dronedarone patients. Dronedarone patients were younger, healthier per Deyo-Charlson Index (DCI) and CHADS2 score, and less likely to have underlying heart disease (all p-values<0.05). In the propensity score matching process 838 patients with comparable baseline characteristics were selected in each group. Median follow up was 552 days in the amiodarone cohort and 412 days in the dronedarone cohort. Among patients without HF history, new onset HF incidence rate was 34.6 per 100 person-year in amiodarone cohort and 19.1 per 100 person-year in dronedarone cohort (IRR=1.61, 95% CI: 1.30-2.01, p<0.01). The incidence rate for HF hospitalization was also higher in amiodarone patients-- 10.7 per 100 person-year against 7.8 per 100 person-year for dronedarone (IRR=1.39, 95% CI: 1.02-1.85, p=0.03). For IS, the incidence rate was 1.68 per 100 person-year in amiodarone vs. 0.84 in dronedarone but results did not reach statistical significance (IRR=1.91, 95% CI: 0.84-4.30, p=0.12); for TIA, it was 3.67 vs. 2.35 for amiodarone and dronedarone respectively (IRR=2.01, 95% CI: 1.14-3.57, p=0.02). Conclusions: In a propensity score matched observational cohort study, amiodarone use was associated with higher incidence rate of new onset HF, HF hospitalizations, and TIA as identified from claims. This finding differs from other clinical studies. Future observational cohort studies should incorporate medical record review for validation since information from claims might be insufficient to fully account for underlying patient risk status, or accurately determine if HF was new onset. Key words: amiodarone; dronedarone; atrial fibrillation; heart failure.