Statin Therapy for the Prevention of Atrial Fibrillation

A Meta-analysis of Randomized Controlled Trials

Zhongsu Wang; Yong Zhang; Mei Gao; Jiangrong Wang; Qing Wang; Xiaojun Wang; Lequn Su; Yinglong Hou

Disclosures

Pharmacotherapy. 2011;31(11):1051-1062. 

In This Article

Abstact and Introduction

Abstact

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 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% CI 0.27–0.66), especially in the dose range of 10–40 mg/day (OR 0.29, 95% 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.

Introduction

Atrial fibrillation is the most commonly encountered cardiac arrhythmia in clinical practice and results in substantial morbidity and mortality, as well as increased medical costs.[1,2] In the United States, the prevalence of atrial fibrillation increases with advancing age, from 0.1% among adults younger than 55 years to 9.0% in persons aged 80 years or older.[1]

Pharmacotherapy plays an important role in the management of atrial fibrillation. As the traditional antiarrhythmic drugs have shown unsatisfactory effects,[3] much recent therapeutic effort with "upstream therapies" has been expended to slow or halt the progression of atrial fibrillation. These therapies include angiotensinconverting enzyme inhibitors, angiotensin II receptor blockers, aldosterone antagonists, 3- hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), and omega-3 polyunsaturated fatty acids.[4,5]

Patients in sinus rhythm with a history of previous atrial fibrillation, those undergoing cardiac surgery, or those who have experienced an acute coronary syndrome are at increased risk of developing atrial fibrillation. The efficacy of statins for the prevention of atrial fibrillation has already been explored.[6–26] In addition, two metaanalyses were recently published.[27,28] The first meta-analysis suggested that statins were more effective in secondary prevention of atrial fibrillation than for new-onset or postoperative atrial fibrillation.[27] It was suggested, however, that this conclusion might be uncertain because none of the results of the subset analyses were statistically significant, which may be explained in part by the lower number of patients with new-onset or postoperative atrial fibrillation. Furthermore, the second meta-analysis revealed that the reduced risk of postoperative atrial fibrillation was related to the specific statin used.[28] Clearly, the primary and secondary preventive effects of statins require further study. Moreover, the efficacy of the several statins available, as well as the influence of drug dosage, has not been studied in detail. Therefore, we performed a meta-analysis of randomized controlled trials (RCTs) to further investigate the primary and secondary preventive effects of statins and to evaluate the efficacy of individual statins and their dosages.

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