Effect of lipid lowering on new-onset atrial fibrillation in patients with asymptomatic aortic stenosis: The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study
ABSTRACT Lipid-lowering drugs, particularly statins, have anti-inflammatory and antioxidant properties that may prevent atrial fibrillation (AF). This effect has not been investigated on new-onset AF in asymptomatic patients with aortic stenosis (AS).
Asymptomatic patients with mild-to-moderate AS (n = 1,421) were randomized (1:1) to double-blind simvastatin 40 mg and ezetimibe 10 mg combination or placebo and followed up for a mean of 4.3 years. The primary end point was the time to new-onset AF adjudicated by 12-lead electrocardiogram at a core laboratory reading center. Secondary outcomes were the correlates of new-onset AF with nonfatal nonhemorrhagic stroke and a combined end point of AS-related events.
During the course of the study, new-onset AF was detected in 85 (6%) patients (14.2/1,000 person-years of follow-up). At baseline, patients who developed AF were, compared with those remaining in sinus rhythm, older and had a higher left ventricular mass index a smaller aortic valve area index. Treatment with simvastatin and ezetimibe was not associated with less new-onset AF (odds ratio 0.89 [95% CI 0.57-1.97], P = .717). In contrast, age (hazard ratio [HR] 1.07 [95% CI 1.05-1.10], P < .001) and left ventricular mass index (HR 1.01 [95% CI 1.01-1.02], P < .001) were independent predictors of new-onset AF. The occurrence of new-onset AF was independently associated with 2-fold higher risk of AS-related outcomes (HR 1.65 [95% CI 1.02-2.66], P = .04) and 4-fold higher risk of nonfatal nonhemorrhagic stroke (HR 4.04 [95% CI 1.18-13.82], P = .03).
Simvastatin and ezetimibe were not associated with less new-onset AF. Older age and greater left ventricular mass index were independent predictors of AF development. New-onset AF was associated with a worsening of prognosis.
- American heart journal 10/2012; 164(4):e11. DOI:10.1016/j.ahj.2012.07.016 · 4.56 Impact Factor
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ABSTRACT: PURPOSE OF REVIEW: Whether statins may prevent atrial fibrillation remains a subject of debate. An updated systematic review of randomized controlled trials with statins that collected data on the incidence or recurrence of atrial fibrillation was performed. RECENT FINDINGS: Thirty-two published studies with 71 005 patients were included in the analysis. Overall, the use of statins was significantly associated with a decreased risk of atrial fibrillation compared with controls [odds ratio (OR) 0.69, 95% confidence interval (CI) 0.57-0.83, P < 0.0001] with heterogeneous results. The benefit of statin therapy appeared highly significant for the prevention of postoperative atrial fibrillation (homogeneous OR 0.37, 95% CI 0.28-0.51, P < 0.00001). Benefit was not apparent for the prevention of new-onset atrial fibrillation (OR 1.00, 95% CI 0.86-1.15, P = 0.95) but was significant for secondary prevention of atrial fibrillation (OR 0.57, 95% CI 0.36-0.91, P = 0.02 with significant heterogeneity). There was no reduction in the risk of atrial fibrillation with more intensive vs. standard statin regimens (OR 1.01, 95% CI 0.77-1.32, P = 0.96). SUMMARY: The use of statins was significantly associated with a decreased risk of atrial fibrillation in patients with sinus rhythm. The highest benefit was seen for the prevention of postoperative atrial fibrillation and in secondary prevention of atrial fibrillation, with a heterogeneity that deserves further clarification.Current opinion in cardiology 11/2012; 28. DOI:10.1097/HCO.0b013e32835b0956 · 2.59 Impact Factor
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ABSTRACT: BACKGROUND: Left atrial (LA) size and function change with chronically increased left ventricular (LV) filling pressures. It remains unclear whether these variations in LA parameters can predict new-onset atrial fibrillation (AF) in asymptomatic patients with aortic stenosis (AS). METHODS: Data were obtained in asymptomatic patients with mild-to-moderate AS (2.5≤ transaortic Doppler velocity ≤4.0m/s), preserved LV ejection fraction (EF), no previous AF, and were enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis study. Peak-aortic velocity, LA(max) volume & LA(min) volume were measured by echocardiography. LA conduit (LA(con)) volume was defined as LV stroke volume-LA stroke volume. LA function was expressed as LA-EF (LA(max)-LA(min) volume/LA(max)). RESULTS: In the 1159 patients included, new-onset AF occurred in 71 patients (6.1%) within a mean follow-up of 4.2±0.9years. Mean age was 66±9.7years, aortic valve area index 0.6±0.2cm(2)/m(2), LV mass 99.2±29.7g/m(2), LA(max) volume 34.6±12.0mL/m(2), LA(min) volume 17.9±9.3mL/m(2), LA-EF 50±15% and LA(con) volume 45±21mL/m(2). Baseline LA(min) volume predicted new-onset AF in Cox multivariable analysis (HR:2.3 [95%CI:1.3-4.4], P<0.01), and added prognostic information on AF development beyond conventional risk factors (likelihood ratio, P<0.01). In comparison of c-indexes LA(min) volume was superior to all other LA measurements. Net reclassification index improved by 15.9% when adding LA(min) volume to a model with classic risk factors for AF (P=0.01). CONCLUSION: LA(min) volume independently predicted new-onset AF in patients with asymptomatic AS and was superior to LA-EF, LA(con) and LA(max) volumes and conventional risk factors.International journal of cardiology 02/2013; 168(3). DOI:10.1016/j.ijcard.2013.01.060 · 6.18 Impact Factor