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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.

Recent case reports provided alarming signals that treatment with bortezomib might be associated with cardiac events. In all reported cases, patients experiencing cardiac problems were previously or concomitantly treated with other chemotherapeutics including cardiotoxic anthracyclines. Therefore, it is difficult to distinguish which components of the therapeutic regimens contribute to cardiotoxicity. Here, we addressed the influence of bortezomib on cardiac function in rats that were not treated with other drugs. Rats were treated with bortezomib at a dose of 0.2 mg/kg thrice weekly. Echocardiography, histopathology, and electron microscopy were used to evaluate cardiac function and structural changes. Respiration of the rat heart mitochondria was measured polarographically. Cell culture experiments were used to determine the influence of bortezomib on cardiomyocyte survival, contractility, Ca(2+) fluxes, induction of endoplasmic reticulum stress, and autophagy. Our findings indicate that bortezomib treatment leads to left ventricular contractile dysfunction manifested by a significant drop in left ventricle ejection fraction. Dramatic ultrastructural abnormalities of cardiomyocytes, especially within mitochondria, were accompanied by decreased ATP synthesis and decreased cardiomyocyte contractility. Monitoring of cardiac function in bortezomib-treated patients should be implemented to evaluate how frequently cardiotoxicity develops especially in patients with pre-existing cardiac conditions, as well as when using additional cardiotoxic drugs.