Abstract
Dronedarone is an anti-arrhythmic drug (AAD) originally approved for the treatment of atrial arrhythmias. The effectiveness and side effects of dronedarone have not been adequately compared to other commonly used AADs using observational data. We compared rates of recurrent atrial arrhythmias, incidence of side effects, and discontinuation rates of dronedarone to another class III AAD, dofetilide. We included patients from a single academic medical center between 2003 and 2010. Chart review was utilized to collect historical data of baseline clinical characteristics, side effects, arrhythmia recurrence, and drug discontinuation. Propensity score matching was used to balance baseline covariates. Cox-proportional hazard models were used to compare rates of recurrence between dronedarone and dofetilide. Patients were excluded if they failed to acutely achieve sinus rhythm, developed side effects leading to immediate discontinuation, or did not have sufficient follow-up. The final analysis included 127 dofetilide patients and 57 dronedarone patients. Fifty-nine patients (46.5%) experienced recurrence in the dofetilide group within the first year of treatment compared to 42 dronedarone patients (71.2%) (p<0.01). The adjusted hazard rate of recurrence was 2.42 times greater for dronedarone compared to dofetilide (95% CI: 1.44, 4.07; p-value<0.01). Side effects leading to drug discontinuation, including significant QT prolongation, developed more frequently with dofetilide (24.1% vs. 9.9%; p<0.01). Dronedarone is less effective than dofetilide in arrhythmia suppression. Our findings suggest dofetilide is associated with more serious side effects and a higher rate of discontinuation.
Highlights
A variety of anti-arrhythmic drugs (AADs) are used to suppress arrhythmias encountered in clinical practice[1]
This study suggested the efficacy of dronedarone and dofetilide to be similar, with dronedarone being associated with a great risk of cardiacrelated admissions
Since we are comparing two treatments, we modeled the probability of being treated with dronedarone – the newer agent being compared to the older therapy, dofetilide
Summary
A variety of anti-arrhythmic drugs (AADs) are used to suppress arrhythmias encountered in clinical practice[1]. AADs exert their pharmacologic effect by blocking ion channel currents in myocardial cells. Class III AADs block the delayed potassium rectifier current (IKr) and prolong phase 3 repolarization of the individual cell action potential. While this mechanism of action is aimed at suppressing arrhythmias, it can predispose to other, potentially more dangerous ones. The clinical use of AADs has been somewhat disappointing due to limited effectiveness and the occurrence of cardiac and systemic side effects
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