Randomized dose-response study of rosuvastatin in Japanese patients with hypercholesterolemia

Abstract

Rosuvastatin is a novel statin that has been shown to produce large dose-dependent reductions in low-density lipoprotein cholesterol (LDL-C) in Western hypercholesterolemic patients. Rosuvastatin dose response was assessed in a randomized, double-blind phase II trial in which 112 Japanese patients with fasting LDL-C > 160 and < 220 mg/dl and triglycerides < 300 mg/dl received placebo or rosuvastatin 1, 2.5, 5, 10, 20, or 40 mg once daily for 6 weeks. LDL-C change from baseline showed a linear dose response (p < 0.0001 for slope of regression line) over the rosuvastatin dose range, with each doubling of dose producing an additional 5.12% reduction. Mean reductions (least-squares mean percentage change from baseline from ANOVA) in LDL-C were 35.8% to 66.0% and significantly different from placebo at all doses (p < 0.0001). Linear dose response was also observed for total cholesterol (TC) and apolipoprotein (apo) B, but not for triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), or apo A-I or A-II. Mean changes at 6 weeks were - 25.5 to - 45.1% for TC, - 16.0 to - 26.2% for TG, + 7.5 to + 12.8% for HDL-C, - 31.9 to - 57.8% for apo B, + 5.5 to + 10.0% for apo A-I, and + 0.4 to + 8.1% for apo A-II. Rosuvastatin was well tolerated. Although there was some suggestion of increased frequency of treatment-related adverse events at higher doses, there were no clear dose relationships in safety parameters. Only one patient withdrew from the study because of a treatment-related adverse event. No patients had clinically significant elevations in liver transaminases or creatine kinase. Rosuvastatin produces good dose-related reductions in LDL-C and beneficial changes in other lipid fractions in Japanese hypercholesterolemic patients and is well tolerated.