Background-Atrial fibrillation (AF) after cardiac surgery is associated with increased risk of complications, length of stay, and cost of care. Observational evidence suggests that patients who have undergone previous statin therapy have a lower incidence of postoperative AF. We tested this observation in a randomized, controlled trial. Methods and Results-Two hundred patients undergoing elective cardiac surgery with cardiopulmonary bypass, without previous statin treatment or history of AF, were enrolled. Patients were randomized to atorvastatin (40 mg/d, nϭ101) or placebo (nϭ99) starting 7 days before operation. The primary end point was incidence of postoperative AF; secondary end points were length of stay, 30-day major adverse cardiac and cerebrovascular events, and postoperative C-reactive protein (CRP) variations. Atorvastatin significantly reduced the incidence of AF versus placebo (35% versus 57%, Pϭ0.003). Accordingly, length of stay was longer in the placebo versus atorvastatin arm (6.9Ϯ1.4 versus 6.3Ϯ1.2 days, Pϭ0.001). Peak CRP levels were lower in patients without AF (Pϭ0.01), irrespective of randomization assignment. Multivariable analysis showed that atorvastatin treatment conferred a 61% reduction in risk of AF (odds ratio 0.39, 95% confidence interval 0.18 to 0.85, Pϭ0.017), whereas high postoperative CRP levels were associated with increased risk (odds ratio 2.0, 95% confidence interval 1.2 to 7.0, Pϭ0.01). The incidence of major adverse cardiac and cerebrovascular events at 30 days was similar in the 2 arms. Conclusions-Treatment with atorvastatin 40 mg/d, initiated 7 days before surgery, significantly reduces the incidence of postoperative AF after elective cardiac surgery with cardiopulmonary bypass and shortens hospital stay. These results may influence practice patterns with regard to adjuvant pharmacological therapy before cardiac surgery.
Background-Impaired endothelial function is a key event in the atherosclerosis process and predicts future cardiovascular events in subjects with and without coronary artery disease (CAD). We performed the first prospective study evaluating whether early measurement of brachial artery endothelium-dependent dilation (flow-mediated dilation [FMD]) after coronary stenting could predict occurrence of in-stent-restenosis. Methods and Results-The study population included 136 patients with single-vessel CAD undergoing percutaneous coronary intervention (PCI) with stenting and at least 6 months of follow-up. All patients underwent ultrasound detection of brachial artery reactivity 30 days after PCI; FMD was investigated before and after 5 minutes of occlusion of the brachial artery, and nitroglycerin-mediated dilation was investigated before and after administration of sublingual nitrates. Clinical in-stent restenosis was demonstrated in 20 patients (15%), whereas 116 patients (85%) remained free of signs or symptoms of recurrent ischemia. FMD was significantly impaired in patients with restenosis versus those without restenosis (percent diameter variation 4.6Ϯ5.8% versus 9.5Ϯ6.6%, Pϭ0.002); moreover, 4% of patients with FMD Ն7% (median value) developed in-stent restenosis versus 28% of those with FMD Ͻ7% (Pϭ0.0001). On multivariate analysis, FMD was the strongest predictor of restenosis (OR 4.5, 95% CI 2.4 to 12.0); conversely, nitroglycerin-mediated dilation did not independently predict the risk of restenosis (OR 2.4, 95% CI 0.8 to 6.3). Conclusions-This is the first prospective study indicating that impaired FMD independently predicts occurrence of in-stent restenosis in patients undergoing PCI. Early evaluation of endothelial function after stenting may represent a useful screening tool to stratify patients according to future risk of restenosis.
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