Statin use and development of atrial fibrillation: A systematic review and meta-analysis of randomized clinical trials and observational studies

Background: Inflammation and oxidative stress have been associated with atrial fibrillation (AF). On the other hand, accumulating evidence suggests that statins may have antiarrhythmic effects due to pleiotropic properties. However, inconsistent results have been reported with respect to AF. Aims: We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) and observational studies to examine the association between statin use and development of AF. Methods: PubMed, Cochrane clinical trials database, and EMBASE were searched until November 2006. In addition, a manual search was performed using all review articles on this topic, reference lists of papers, and abstracts from conference reports. Of the 309 initially identified studies, 6 RCTs and 10 observational studies with 7041 patients were finally analyzed. Results: The analysis of RCTs showed no significant effect of statins on AF development (RR = 0.76, 95% CI: 0.55-1.05, P = 0.09), and significant heterogeneity between individual studies (P = 0.0008, I-2 = 74.0%). Subgroup analysis revealed that differences in AF detection methodology may be the cause of heterogeneity. The analysis of observational studies demonstrated that statin use reduced the relative risk for AF by 23% ( 95% CI: 0.70-0.85, Z = 4.95, P < 0.00001) without significant differences between the trials (P = 0.08, I-2 = 41.2%). This favorable effect was greatest in the post-operative patients (RR = 0.61, 95% CI: 0.49-0.76, Z = 4.30, P < 0.0001). Conclusion: Our meta-analysis suggests that statins may be effective in AF prevention especially in the post-operative setting. However, there are insufficient data for the widespread use of statins solely for AF prevention. Larger RCTs with long-term follow-up in different clinical settings, and more sensitive methods of arrhythmia detection are needed to clarify the impact of statins on AF. (c) 2007 Elsevier Ireland Ltd. All rights reserved.