Coadministration of valsartan 160 and 320 mg and simvastatin 20 and 40 mg in patients with hypertension and hypercholesterolemia: a multicenter, 12-week, double-blind, double-dummy, parallel-group superiority study.

BACKGROUND

Together, high blood pressure (BP) and high cholesterol levels constitute a cumulative risk for coronary heart disease (CHD). Elevations in cholesterol increase BP through upregulation of angiotensin type 1 receptors, with a corresponding increase in cholesterol oxidation due to elevations in BP. Hence, control of low-density lipoprotein cholesterol (LDL-C) and BP through coadministration of an antihypertensive and a statin have potential benefit in the management of CHD.

OBJECTIVES

This study examined the dose response to simvastatin 20 and 40 mg in reducing LDL-C and the efficacy and tolerability of a high dose of valsartan (320 mg) when administered with simvastatin.

METHODS

In this multicenter, 12-week, double-blind, double-dummy, parallel-group superiority study, patients with hypertension and hypercholesterolemia were randomized to receive valsartan 160 mg along with simvastatin 20 or 40 mg. At week 6, valsartan was titrated upward to 320 mg in both groups. The primary efficacy variable was the change in LDL-C, calculated using the Friedewald formula or measured directly (depending on triglyceride levels) and analyzed for superiority. Secondary efficacy variables were the change in LDL-C and the proportion of patients achieving LDL-C and BP control. Safety assessments included the occurrence of adverse events (AEs) and serious AEs, and changes in hematology and biochemistry variables, vital signs, and findings on physical examinations.

RESULTS

Eight hundred seventy-two patients were randomized to receive double-blind treatment, and the intent-to-treat population included 838 patients. The combination of valsartan 160 mg + simvastatin 40 mg was statistically superior to that of valsartan 160 mg + simvastatin 20 mg in reducing LDL-C at week 6 (least squares mean percent change from baseline: -38.5% vs -33.6%, respectively; P < 0.001); at week 12, the corresponding values were -36.8% in the valsartan 320 mg + simvastatin 40 mg group and -32.7% in the valsartan 320 mg + simvastatin 20 mg group (P = 0.002). Rates of combined LDL-C and BP control at week 6 were 35.1% (146/416) in the valsartan 160 mg + simvastatin 20 mg group and 37.4% (154/412) in the valsartan 160 mg + simvastatin 40 mg group; at week 12, rates of combined control were 50.7% (212/418) in the valsartan 320 mg + simvastatin 20 mg group and 50.0% (206/412) in the valsartan 320 mg + simvastatin 40 mg group. AEs occurred in 24.3% (102/420) of the valsartan 160/320 mg + simvastatin 20 mg group and 22.2% (93/419) of the valsartan 160/320 mg + simvastatin 40 mg group.

CONCLUSIONS

In these patients with hypertension and hypercholesterolemia, coadministration of valsartan and simvastatin was well tolerated and was associated with significant reductions from baseline in BP and LDL-C. Coadministered with valsartan 160/320 mg in the evening, simvastatin 40 mg had superior LDL-C-lowering efficacy to simvastatin 20 mg.