The role of statin therapy in the prevention of atrial fibrillation: a meta-analysis of randomized controlled trials

Abstract

What is already known about this subject: Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia, and AF is associated with relatively higher all-cause mortality in both men and women. However, there are limited treatment options for AF. Statins are hypothesized to have a benefit against arrhythmias in addition to well-established secondary prevention benefit for atherosclerotic coronary artery disease, yet the data are inconsistent

What this study adds: Statin therapy was significantly associated with a decreased risk of incidence or recurrence of AF. The benefit of statin therapy seemed more markedly in secondary prevention than primary prevention. These results provided some evidence for the benefit of statins beyond their lipid-lowering activity

Aims: The use of statins has been suggested to protect against atrial fibrillation (AF) in some clinical observational and experimental studies but has remained inadequately explored. This study was designed to examine whether statins can reduce the risk of AF.

Methods: Meta-analysis of randomized, controlled trials with use of statins on incidence or recurrence of AF was performed.

Results: Twenty studies with 23,577 patients were included in the analysis. Seven studies investigated the use of statins in patients with AF, 11 studies investigated the primary prevention of statins in patients without AF, and two studies investigated mixed populations of patients. The incidence or recurrence of AF occurred in 1543 patients. Overall, statin therapy was significantly associated with a decreased risk of AF compared with control (odds ratio 0.49, 95% confidence interval 0.37-0.65; P < 0.00001). A beneficial effect was found in the atorvastatin subgroup and the simvastatin subgroup, but not in the pravastatin subgroup or the rosuvastatin subgroup. The benefit of statin therapy appeared to be more pronounced in secondary prevention (odds ratio 0.34, 95% confidence interval 0.18-0.64; P < 0.0008) than in primary prevention (odds ratio 0.54, 95% confidence interval 0.40-0.74; P < 0.0001).

Conclusions: Statin therapy was significantly associated with a decreased risk of incidence or recurrence of AF. Heterogeneity was explained by differences in statin types, patient populations and surgery types. The benefit of statin therapy seemed more pronounced in secondary than in primary prevention.

© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Figures

Figure 1

Effect of statin treatment on atrial fibrillation. Abbreviations: ALLHAT, antihypertensive and lipid-lowering treatment to prevent heart attack trial; ARMYDA-3, atorvastatin for reduction of myocardial dysrhythmia after cardiac surgery study; MIRACL, myocardial ischemia reduction with aggressive cholesterol lowering study; SToP AF trial, statin therapy for the prevention of atrial fibrillation trial; WOSCOPS, west of scotland coronary prevention study

Figure 2

Effects of treatment with different statins on atrial fibrillation. Abbreviations: ALLHAT, antihypertensive and lipid-lowering treatment to prevent heart attack trial; ARMYDA-3, atorvastatin for reduction of myocardial dysrhythmia after cardiac surgery study; MIRACL, myocardial ischemia reduction with aggressive cholesterol lowering study; SToP AF trial, statin therapy for the prevention of atrial fibrillation trial; WOSCOPS, west of scotland coronary prevention study

Figure 3

Primary and secondary prevention of atrial fibrillation with statins. Abbreviation: AF, atrial fibrillation; ALLHAT, antihypertensive and lipid-lowering treatment to prevent heart attack trial; ARMYDA-3, atorvastatin for reduction of myocardial dysrhythmia after cardiac surgery study; MIRACL, myocardial ischemia reduction with aggressive cholesterol lowering study; SToP AF trial, statin therapy for the prevention of atrial fibrillation trial; WOSCOPS, west of scotland coronary prevention study

Figure 4

Secondary prevention of atrial fibrillation with statin therapy, either in the with EC group and in the without EC group. Abbreviations: EC, electrical cardioversion; SToP AF trial, statin therapy for the prevention of atrial fibrillation trial

Figure 5

Primary prevention of atrial fibrillation with statins in patients with or without coronary surgery. Abbreviations: ARMYDA-3, atorvastatin for reduction of myocardial dysrhythmia after cardiac surgery study; WOSCOPS, west of scotland coronary prevention study

Figure 6

Evaluation of heterogeneity and publication bias. * Publication bias is not evident; # heterogeneity is not evident; and † the number of trials was too small to allow for evaluation of heterogeneity