Effects of statin therapy on preventing atrial fibrillation in coronary disease and heart failure

doi:10.1016/j.ahj.2007.07.018

American Heart Journal

Volume 154, Issue 6, December 2007, Pages 1140-1145

https://doi.org/10.1016/j.ahj.2007.07.018 Get rights and content

Background

Statins are associated with decreased incidence of life-threatening arrhythmias in patients with cardiomyopathy and reduce death and hospitalization in congestive heart failure (CHF). We hypothesized that statin use will reduce incident atrial fibrillation (AF) in patients with coronary heart disease (CHD), including those with CHF.

Methods

A cohort of 17 741 patients with CHD examined between 1994 and 1997 at 5 Veterans Affairs medical facilities was assembled. Patients with known AF, warfarin treatment, liver disease, or no follow-up visits were excluded. The final cohort included 13783 patients. The primary outcome was time to development of AF. Propensity scores were used to balance statin-treated and untreated patients with respect to baseline characteristics. Time from the initial visit to development of AF was analyzed with a Cox regression model, using statin treatment as a time-varying covariate.

Results

Among the 13 783 patients, 5417 (39%) received statin treatment. Statin-treated patients were younger with fewer comorbid conditions. After propensity adjustment, the baseline characteristics of the statin-treated and untreated patients were similar. During an average follow-up of 4.8 years, 1979 (14%) patients developed AF. In the overall study population there was no difference in AF incidence with statin treatment (hazard ratio 1.0, 95% CI 0.88-1.14, P = .9). However, AF was less common among statin-treated patients with CHF (hazard ratio 0.57, 95% CI 0.33-1.00, P = .04).

Conclusions

We did not find any effect of statin treatment on AF incidence in patients with CHD; however, AF was reduced in a subset of patients with CHF.

Section snippets

Study population

We have used an administrative data set developed for a previous investigation.¹⁶ Briefly, Veterans Affairs (VA) administrative databases, specifically the Patient Treatment Files located in Austin, Tex, and local Veterans Health Information Systems Technology Architecture were used to identify patients with CHD who were examined between January 1, 1994, and December 31, 1996, at any of the 5 medical facilities in the VA Upper Midwest Integrated Service Network. There were 17 741 patients

Baseline characteristics

Of the 13 783 patients with CHD included in this analysis, 5417 (39%) received a prescription for a statin subsequent to the index date and 8366 (61%) did not. In general, the statin-treated patients were younger (64 ± 9 vs 68 ± 10, P < .0001) with fewer noncardiac comorbid conditions than the patients who were not prescribed a statin (Table I). In the year before the index date, statin-treated patients were hospitalized more often for cardiac causes (25% vs 18%, P < .0001) and were more likely

Discussion

This investigation demonstrated that in a large cohort of patients with CHD, statin treatment did not affect the risk of developing AF. The previous studies in this area have not been large enough to adjust for baseline characteristics and medications and have showed opposing results. To overcome these limitations in the present investigation, a large cohort of patients was included and propensity scores were used to balance the statin-treated and untreated patients. We also found that in a

References (39)

A.P. Maggioni et al.
Valsartan reduces the incidence of atrial fibrillation in patients with heart failure: results from the Valsartan Heart Failure Trial (Val-HeFT)
Am Heart J
(2005)
A.K. Vyas et al.
Reduction in ventricular tachyarrhythmias with statins in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II
J Am Coll Cardiol
(2006)
L.B. Mitchell et al.
Are lipid-lowering drugs also antiarrhythmic drugs? An analysis of the Antiarrhythmic Versus Implantable Defibrillators (AVID) Trial
J Am Coll Cardiol
(2003)
J. De Sutter et al.
Lipid lowering drugs and recurrences of life-threatening ventricular arrhythmias in high-risk patients
J Am Coll Cardiol
(2000)
J.J. Goldberger et al.
Effects of statin therapy on arrhythmic events and survival in patients with nonischemic dilated cardiomyopathy
J Am Coll Cardiol
(2006)
C.-W. Siu et al.
Prevention of atrial fibrillation recurrence by statin therapy in patients with lone atrial fibrillation after successful cardioversion
Am J Cardiol
(2003)
Y. Young-Xu et al.
Usefulness of statin drugs in protecting against atrial fibrillation in patients with coronary artery disease
Am J Cardiol
(2003)
A. Tveit et al.
Analysis of pravastatin to prevent recurrence of atrial fibrillation after electrical cardioversion
Am J Cardiol
(2004)
M. Ozaydin et al.
Effect of atorvastatin on the recurrence rates of atrial fibrillation after electrical cardioversion
Am J Cardiol
(2006)
H.B. Rubins et al.
Effectiveness of lipid-lowering medications in outpatients with coronary heart disease in the Department of Veterans Affairs System
Am J Cardiol
(2003)

I.R. Hanna et al.

Lipid-lowering drug use is associated with reduced prevalence of atrial fibrillation in patients with left ventricular systolic dysfunction

Heart Rhythm

(2006)

A. Raina et al.

Statin use in heart failure: a cause for concern?

Am Heart J

(2006)

K.C. Kurian et al.

The effect of statins in heart failure: beyond its cholesterol-lowering effect

J Card Fail

(2006)

J.F. Steiner et al.

The assessment of refill compliance using pharmacy records: methods, validity, and applications

J Clin Epidemiol

(1997)

American Heart Association. Heart disease and stroke statistics—2006 update. Dallas,...

Y. Miyasaka et al.

Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence

Circulation

(2006)

O.D. Pedersen et al.

Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction

Circulation

(1999)

E. Vermes et al.

Enalapril decreases the incidence of atrial fibrillation in patients with left ventricular dysfunction: insight from the Studies Of Left Ventricular Dysfunction (SOLVD) trials

Circulation

(2003)

A.H. Madrid et al.

Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study

Circulation

(2002)

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Statins have been extensively studied as to whether their pleiotropic effects could potentially influence the incidence of AF. Although observational studies suggested a positive association between statin use and the incidence of AF in patients with coronary heart disease or at high risk for cardiovascular disease (89–94), findings from randomized controlled trials were highly heterogeneous (71,95). A meta-analysis of published and unpublished evidence from these trials did not support the suggested beneficial effect of statins on AF (96).
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Dofetilide is a class III antiarrhythmic agent approved for achieving and maintaining sinus rhythm in patients with symptomatic atrial fibrillation. Because of a risk of QT prolongation and VT, patients starting dofetilide need to be hospitalized for 3 days to closely monitor telemetry and electrocardiography. In large clinical trials, <3% of patients had to discontinue dofetilide because of QT prolongation, but data from real-world experience are lacking.
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Young-Xu and colleagues74 studied 449 patients with chronic stable CAD, treated with any statin, followed for an average 5 years and showed a significant reduction in the risk of developing AF (odds ratio: 0.48; 95% confidence interval: 0.28–20.83). However, similar results were not seen in a VA study,75 which looked at 5417 patients who received statin therapy (any brand) in a similar patient profile with CAD and failed to show any reduction in AF recurrence after 4.8 years of follow-up. Smaller randomized prospective studies have shown benefit of statins in reducing AF episodes; however, similar benefits are still to be determined in a larger prospective trial, PAFRIOSIES (Paroxysmal Atrial Fibrillation: Role of Inflammation, Oxidative Stress Injury and Effect of Statins) (ClinicalTrials.gov Identifier: NCT00321802), which is under way and awaiting results.
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In addition to their lipid-lowering properties, statins have also been found to reduce the risk for developing atrial fibrillation in patients with pre-existent CAD or CHF and in those who received cardiac and non-cardiac thoracic surgery [8–11]. However, a comprehensive systematic review and meta-analysis of randomized trials found that the beneficial effect of statins from short term studies enrolling these highly selected patients was not supported by the data from the long term trials [7–12]. While several methodological and clinical differences between the short-term and longer-term trials, and between studies comparing users with never users vs. those comparing high with low cumulative use may explain the inconsistent results [13–15], a possible immediate but not sustained effect of statins on the risk atrial fibrillation still cannot be excluded.
To contain cost, Taiwan's previous National Health Insurance Reimbursement Policy requested that physicians discontinue their patients' statin therapy once the serum cholesterol had reached appropriate levels. This allowed us to evaluate the association between statin continuation and the occurrence of atrial fibrillation/flutter and whether it was modified by chronic kidney disease (CKD) status.
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: This work was supported by the Health Services Research and Development Offices of the Department of Veterans Affairs, Washington, DC. Dr Adabag is supported, in part, by the Department of Veterans Affairs Clinical Science Research & Development Service (grant 04S-CRCOE-001), Washington, DC.

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Clinical InvestigationsCoronary Artery DiseaseEffects of statin therapy on preventing atrial fibrillation in coronary disease and heart failure

Background

Methods

Results

Conclusions

Section snippets

Study population

Baseline characteristics

Discussion

Am Heart J

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

Am J Cardiol

Am J Cardiol

Am J Cardiol

Heart Rhythm

Am Heart J

J Card Fail

J Clin Epidemiol

Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence

Circulation

Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction

Circulation

Enalapril decreases the incidence of atrial fibrillation in patients with left ventricular dysfunction: insight from the Studies Of Left Ventricular Dysfunction (SOLVD) trials

Circulation

Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study

Circulation

Clinical Investigations
Coronary Artery Disease
Effects of statin therapy on preventing atrial fibrillation in coronary disease and heart failure