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Usefulness of statin drugs in protecting against atrial fibrillation in patients with coronary artery diseaseYoung-Xu Y, Jabbour S, Goldberg R, et al.Am J Cardiol 2003; 92:1379-83 Reviewer: K. W. Tim Park, MD
Background:Risk factors for development of atrial fibrillation (AF) are often also risk factors of coronary artery disease (CAD) and include advanced age, male gender, hypertension, and diabetes mellitus.1,2 Additional risk factors for AF are CAD, valve disease and history of congestive heart failure (CHF).1 Clinical trials of statins have clearly demonstrated the beneficial effects of the drugs on some of these risk factors for AF such as primary and secondary prevention of CAD.3-6 In this study, the authors examined if statin use was associated with a reduced incidence of AF in men and women with chronic stable CAD, but without previous AF. Methods:Consecutive patients with documented CAD, seen between December 1992 and November 2000, were screened and followed prospectively. Patients were excluded for prior coronary revascularization, NYHA class III or IV CHF, advanced valvular disease, severe or life-limiting noncardiac illnesses, or history of chronic or paroxysmal AF. Data were accrued through June 2001. Primary end point was the occurrence of AF, confirmed by 12-lead ECG obtained either during routine yearly follow-up or because of new symptoms. The occurrence of AF was compared between users and nonusers of statins of any brand and between statin vs. non-statin cholesterol lowering therapy. The impact of the pattern of statin use (regular vs. intermittent) and duration of use was also examined. Results:A total of 449 patients did not have any of the exclusion criteria and were enrolled in the study. 186 patients were non-users of statins and 263 were users (128 regularly and 135 intermittently). Average follow-up was 5 years (range 1 - 9 years). Baseline characteristics of statin users and nonusers were similar, except that the users were younger (66 ± 9 vs. 71 ± 9, P < 0.01) and more likely to be taking a β-adrenergic blocker (80% vs. 67%, P < 0.02), but had a higher incidence of smoking history (62% vs. 56%, P < 0.03) and were less likely to be on aspirin (90% vs. 93%, P < 0.03). Statin use was associated with about a two-fold reduction in the incidence of AF (18 per 1000 person-years vs. 37 per 1000 person-years) and the reduction remained significant, even after controlling for age, male gender, systolic blood pressure, left ventricular ejection fraction, alcohol consumption, history of CHF, history of myocardial infarction, and the use of a b-adrenergic blocker. Relative risks (RR) of AF showed a decreasing trend as the duration of statin use increased (RR of 0.75 for 1-2 years, 0.44 for 3-4 years, 0.37 for 5-6 years, and 0.17 for 7-8 years). RR of AF were lower among regular users (15 per 1000 person years) compared to intermittent users (21 per 1000 person years). However, RR reduction was not affected by the baseline cholesterol level or the degree of cholesterol reduction. Furthermore, in 124 additional patients who were using non-statin cholesterol lowering medications, the incidence of AF (34 per 1000 person years) was not significantly different from nonusers. Discussion and Comments:This study demonstrated the use of statins was associated with a reduction in the risk of developing new AF. This association appeared to be dose-dependent, since regular users and longer duration of use appeared to benefit more from statins. The effect also appeared to be independent of any reduction in cholesterol by statins, since the degree of cholesterol reduction by statins and the use of non-statin cholesterol lowering medications were not associated with a reduction in AF. This study adds to the growing list documenting the pleiotropic benefits of statins, in addition to cholesterol reduction and prevention of CAD. Statins have also been shown to reduce aortic valve calcification,7,8 thus possibly slowing the progression of native aortic valve stenosis. Degeneration of the bioprosthetic aortic valve was also reduced by statin therapy.9 In a follow-up of 167 patients, statin use was associated in a 3-fold reduction in the rate of decrease in the effective orifice area and a 5-fold reduction in the rate of increase of mean gradient across the bioprosthetic valve.9 This association remained significant even after controlling for age, diabetes mellitus, hypertension, CAD, hypercholesterolemia, and body mass index. In the perioperative period, statin use has been associated with a reduced mortality after vascular surgery,10 as was reviewed in the December 2003 issue of the newsletter (http://www.scahq.org/sca3/newsletters/2003dec/lit1.shtml). The benefits of statins were much more than can be explained by cholesterol reduction alone. Pravastatin has been shown to decrease plasma concentrations of C-reactive protein, a key marker of inflammation, independent of changes in serum lipids.11 Statins may have pleiotropic effects including anti-inflammatory effect, preservation of endothelial function, and stabilization of vascular plaques.12 Additional studies on the benefits of statins in the perioperative period as well as on the mechanisms of the benefits are needed. References:
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