Effect of lipid lowering on new-onset atrial fibrillation in patients with asymptomatic aortic stenosis: the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study.

Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark.
American heart journal (Impact Factor: 4.65). 04/2012; 163(4):690-6. DOI: 10.1016/j.ahj.2012.01.026
Source: PubMed

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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: New-onset atrial fibrillation (AF) is reported to increase the risk of death in myocardial infarction (MI) patients. However, previous studies have reported conflicting results and no data exist to explain the underlying cause of higher death rates in these patients. All patients with first acute MI between 1997 and 2009 in Denmark, without prior AF, were identified from Danish nationwide administrative registers. The impact of new-onset AF on all-cause mortality, cardiovascular death, fatal/nonfatal stroke, fatal/nonfatal re-infarction and noncardiovascular death, were analyzed by multiple time-dependent Cox models and additionally in propensity score matched analysis. In 89 703 patients with an average follow-up of 5.0±3.5 years event rates were higher in patients developing AF (n=10 708) versus those staying in sinus-rhythm (n=78 992): all-cause mortality 173.9 versus 69.4 per 1000 person-years, cardiovascular death 137.2 versus 50.0 per 1000 person-years, fatal/nonfatal stroke 19.6/19.9 versus 6.2/5.6 per 1000 person-years, fatal/nonfatal re-infarction 29.0/60.7 versus 14.2/37.9 per 1000 person-years. In time-dependent multiple Cox analyses, new-onset AF remained predictive of increased all-cause mortality (HR: 1.9 [95% CI: 1.8 to 2.0]), cardiovascular death (HR: 2.1 [2.0 to 2.2]), fatal/nonfatal stroke (HR: 2.3 [2.1 to 2.6]/HR: 2.5 [2.2 to 2.7]), fatal/nonfatal re-infarction (HR: 1.7 [1.6 to 1.8]/HR: 1.8 [1.7 to 1.9]), and non- cardiovascular death (HR: 1.4 [1.3 to 1.5]) all P<0.001). Propensity-score matched analyses yielded nearly identical results (all P<0.001). New-onset AF after first-time MI is associated with increased mortality, which is largely explained by more cardiovascular deaths. Focus on the prognostic impact of post-infarct AF is warranted.
    Journal of the American Heart Association. 01/2014; 3(1):e000382.
  • [Show abstract] [Hide abstract]
    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; · 6.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Statins are the cornerstone of lipid-modifying therapy for dyslipidemias and reducing cardiovascular events. Recent US guidelines have shifted away from the concept of cholesterol targets and are encouraging moderate-to-high statin intensity. However, residual risk and statin intolerance remains a significant challenge. Therapies beyond the statins, for combination or monotherapy, include fibrates, ezetimibe, bile acid sequestrants, n-3 fatty acids and niacin. Both the antisense oligonucleotide, mipomersen, and the microsomal triglyceride transfer protein inhibitor, lomitapide, have been approved by the US FDA for use in homozygous familial hypercholesterolemia. The first gene replacement therapy for lipoprotein lipase deficiency has also been approved. The cardiovascular benefit of treating elevated lipoprotein(a) in cardiovascular disease risk prevention remains unproven.
    Expert Review of Cardiovascular Therapy 02/2014;