COMPARATIVE EFFECTIVENESS OF ANTIARRHYTHMIC DRUG THERAPY IN ATRIAL FIBRILLATION: FOCUS ON CARDIOVASCULAR HOSPITALIZATION AND MORTALITY OUTCOMES

Purpose: The objective of this systematic review was to evaluate the evidence for the effect of antiarrhythmic drug (AAD) therapy on CV hospitalization and CV mortality in atrial fibrillation (AF).

Method: We searched the MEDLINE, EMBASE and  Cochrane Clinical Trial Registry databases to identify English-language articles investigating the effects of AADs on  outcomes of cardiovascular (CV) hospitalization and CV mortality. Studies were not restricted by year of publication; the earliest included study was published in 1973. We excluded studies involving non-AF patients, patients <18 years, sample sizes <40, follow-up periods <90 days, studies of non-comparative design, and reports of previously published data. Study quality and applicability was assessed using Agency for Healthcare Research and Quality (AHRQ) criteria.

Result: Of 4,557 identified articles, 38 studies met our criteria for analysis, including 21 studies [19 randomized controlled trials (RCTs)] with the endpoint of CV hospitalization  and 29 studies (24 RCTs) with the endpoint of CV mortality. Among these 38 studies, there was wide variation in definition of CV endpoints. 13 of 38 studies (34%) compared multidrug strategies of rate- versus rhythm-control, while 19 of 38 (50%) studies evaluated individual AADs. Among the few studies examining the effect of individual AADs on CV hospitalization (n=5), the ATHENA trial of dronedarone was rated as the highest quality study.  There were no studies comparing head-to-head treatment effects of individual AADs on CV hospitalization. A large proportion of excluded articles evaluated outcomes of AF recurrence rather than CV hospitalization or CV mortality.

Conclusion: Despite a large number of observational studies and RCTs of AADs in AF, few studies have examined treatment effects on CV hospitalization and CV mortality. The applicability of the identified studies is limited by comparisons of multidrug strategies and wide variation in CV endpoint definitions. We identified no studies with head-to-head efficacy or effectiveness comparisons of individual AADs for CV hospitalization. The limited evidence for the impact of individual AADs on CV hospitalization and CV mortality prevents meaningful assessment of the comparative effectiveness of individual AADs.