Statin Therapy for the Prevention of Atrial Fibrillation: A Meta-analysis of Randomized Controlled Trials

Study Objectives. To assess the efficacy of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) for primary and secondary prevention of atrial fibrillation, and to evaluate the efficacy of individual statins and their dosages. Design. Meta-analysis of 20 randomized controlled trials. Patients. A total of 32,311 patients who received either a statin (16,203 patients) or a placebo or active control regimen (16,108 patients) for either primary or secondary prevention of atrial fibrillation as part of a research study. Measurements and Main Results. A systemic literature search of MEDLINE, EMBASE, and the Cochrane Controlled Trials Register was performed to identify randomized controlled trials involving the prevention of atrial fibrillation with statin therapy. Effect size was expressed as odds ratio (OR) with 95% confidence interval (CI). Subgroup analysis was performed to explore the reasons for heterogeneity. Of the 20 trials, atorvastatin was studied in 11, pravastatin in five, rosuvastatin in three, and simvastatin in one. Overall, among the 32,311 patients in these trials, the risk of atrial fibrillation was significantly reduced by statins (OR 0.59, 95% CI 0.45-0.76), and the drugs were effective for both primary prevention (OR 0.67, 95% CI 0.51-0.88) and secondary prevention (OR 0.40, 95% CI 0.20-0.83). Secondary prevention was not superior to primary prevention, however. A significant benefit was observed in the atorvastatin-treated subgroup (OR 0.43, 95% Cl 0.27-0.66), especially in the dose range of 10-40 mg/day (OR 0.29, 95% CI 0.19-0.45). No protective effect was observed in the pravastatin subgroup (OR 1.03, 95% CI 0.77-1.37). Conclusion. This meta-analysis suggests that statin therapy is useful for the prevention of atrial fibrillation. The benefit of statins in secondary prevention was significant but not superior to primary prevention. Atorvastatin was more effective than pravastatin, and its effects were dose related, with lower doses being more effective. The number of trials focusing on individual drugs is still insufficient, and more randomized controlled trials are necessary to further support these conclusions.