Early effects of statin therapy on endothelial function and microvascular reactivity in patients with coronary artery disease

Background Recent data suggest an early outcome benefit with reduction in cholesterol using statin therapy in patients with coronary artery disease (CAD). This may be caused by effects of low-density lipoprotein cholesterol (LDL-C) reduction on endothelial function and vascular reactivity in the coronary bed. The aim of this randomized placebo-controlled study was to examine the early effects of important reductions in LDL-C on myocardial perfusion and peripheral endothelial function. Methods and Results Seventy-two patients with CAD and LDL-C between 3.0 and 5.9 mmol/L (116-228 mg/dL) were randomized to receive simvastatin 20 mg daily, pravastatin 40 mg daily, or placebo for 8 weeks. At baseline, 2 weeks, and 8 weeks, patients underwent dynamic positron emission tomography perfusion imaging to quantify the retention of rubidium-82 as a measure of myocardial flow at rest and after dipyridamole stress. Patients also underwent brachial artery ultrasound to measure endothelium-dependent flow-mediated vasodilatation. At 2 and 8 weeks, the simvastatin and pravastatin groups showed a significant reduction (P < .001) in LDL-C compared with placebo. At 8 weeks, simvastatin led to an improvement in flow-mediated vasodilatation compared with placebo (6.86% ± 4.4% vs 3.44% ± 4.0%, P < .05), whereas pravastatin was not significantly different than placebo (5.62% ± 4.1% vs 3.44% ± 4.0%, P = NS). Despite this improvement in peripheral endothelial function with simvastatin, there were no significant differences observed in global stress flow and coronary flow reserve at 8 weeks with either drug. Conclusions Short-term LDL reduction with simvastatin therapy improves peripheral endothelial function in patients with stable CAD, although an early effect on coronary vascular reactivity could not be demonstrated.