Clinical question: Does the new antiarrhythmic agent dronedarone, an amiodarone derivative, reduce the incidence of stroke in patients with persistent or paroxysmal atrial fibrillation and at least one risk factor for vascular events?

Background: Antiarrhythmic therapy has not been shown to reduce stroke risk in the treatment of chronic atrial fibrillation. A sub-group analysis of a recent multicentered, international, industry-sponsored, randomized trial of the new antiarrhythmic dronedarone, suggested a potential reduction in stroke risk when compared with placebo.

Study design: Post-hoc analysis of a previous prospective, randomized, placebo-controlled, double-blinded, parallel-arm trial.

Setting: 551 centers in 37 countries.

Synopsis: In addition to anticoagulation and rate control, 4,628 patients with atrial fibrillation and at least one risk factor for cardiovascular (CV) hospitalization were randomized to dronedarone versus placebo. The study assessed the primary outcomes of stroke, acute coronary syndromes, CV, and total mortality.

The dronedarone arm experienced a 0.6% absolute risk reduction (ARR) of stroke {(number-needed-to-treat (NNT) 167); relative risk reduction (RRR) 33%; P=0.027}; 0.7% ARR of “stroke or transient ischemic attack” (NNT 143; RRR 30%; P=0.031); 1.7% ARR of “stroke, ACS, or CV death,” (NNT 59; RRR 31%; P<0.001); and a 1.6% ARR of “stroke, ACS, or all-cause mortality” (NNT 63; RRR 24%; P=0.002). In further subgroup analysis, only the 65% of patients had CHADS2 scores =2, benefited (RR stroke 0.50; 95% CI, 0.32-0.79).

The results are thought-provoking, and suggest there could be more than antiarrhythmic effects of dronedarone (such as antithrombotic, antihypertensive, or neuroprotective effects). However, given the limitations of the study (post-hoc analysis, an unclear mechanism of action, and strokes were not adjudicated) and suggests somewhat different conclusions than the prior AFFIRM trial (NEJM 2002;347:1825), which looked at rate versus rhythm control in patients on the parent drug amiodarone, and was not associated with decreased risk of stroke, more research is needed.

Bottom line: At present, the mainstay of stroke prevention in atrial fibrillation should remain rate control, anticoagulants, and antiplatelet agents.

Citation: Connolly SJ, Crijns HJ, Torp-Pedersen C, et al. Analysis of stroke in ATHENA: a placebo-controlled, double-blinded, parallel-arm trial to assess the efficacy of dronedarone 400 mg BID for the prevention of cardiovascular hospitalization or death from any cause in patients with atrial fibrillation/atrial flutter. Circulation. 2009;120(13):1174-1180.

Reviewed for TH eWire by Bhaskar Arora, MD, Thomas Barrett, MD, MCR, FHM, Honora Englander, MD, Stephanie Halvorson, MD, Alan J. Hunter, MD, David Kagen, MD, Blake Lesselroth, MD, MBI, Portland Veterans Affairs Medical Center and Division of Hospital Medicine, Oregon Health & Science University.