Simvastatin but not ezetimibe reduces sympathetic activity despite similar reductions in cholesterol levels

The relationship between the sympatholytic effects of statins and their lipid-lowering activity remains unclear. Ezetimibe lowers cholesterol, but its sympatholytic activity is unknown. The purpose of study was to compare the influence of equipotent doses of simvastatin and ezetimibe on sympathetic activity. This randomized double-blinded study was performed in 22 hypertensive patients (age, 45.6 ± 2.2 years; female/male, 2/20) with untreated hypercholesterolemia. The subjects were administered 20 mg/d of simvastatin (n = 11) or 20 mg/d of ezetimibe (n = 11) for 6 weeks. Pre- and post-treatment measurements of muscle sympathetic nerve activity (MSNA), baroreceptor control of heart rate (baroreflex sensitivity), and impedance cardiography were recorded. Simvastatin and ezetimibe produced similar reductions of total (-58.0 ± 23.4 vs. -45.2 ± 17.2 mg/dL; P = .15, respectively) and low-density lipoprotein cholesterol (-52.6 ± 20.9 vs. -37.9 ± 17.6 mg/dL; P = .09, respectively). There was a significant difference in the effect of simvastatin and ezetimibe on muscle sympathetic nerve activity (-8.5 ± 5.1 vs. -0.7 ± 3.5 bursts/min; P = .0005). Simvastatin improved baroreflex sensitivity as compared with ezetimibe (10.0 ± 14.3 vs. -2.8 ± 6.1 ms/mm Hg; P = .01). There was no difference in the effect of both treatments on blood pressure, heart rate, cardiac output, stroke volume, total peripheral resistance, high-density lipoprotein, and triglycerides. Simvastatin reduced sympathetic activity via lipid-independent mechanisms, but ezetimibe exerts no sympatholytic effects.