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: 4.46). 04/2012; 163(4):690-6. DOI: 10.1016/j.ahj.2012.01.026
Source: PubMed


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.

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    • "Some studies have argued that AF is merely a risk marker of death, and not a causal mediator of MI.29–30 However, there is evidence to suggest AF is associated with impairment of endothelial function even in the absence of heart failure or hypertension which could explain the increased incidence of AF associated with ischemia‐reperfusion injury after MI.31 Interestingly, inflammation has been demonstrated to be important not only in AF but also in MI pathophysiology.32–33 C‐reactive protein (CRP) has been shown to reduce nitric oxide production in endothelial cells and increase endothelial expression of adhesion molecules.33 "
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    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 12/2014; 3(1):e000382. DOI:10.1161/JAHA.113.000382 · 4.31 Impact Factor

  • American heart journal 10/2012; 164(4):e11. DOI:10.1016/j.ahj.2012.07.016 · 4.46 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.
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