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.

Effects of Rosuvastatin on Low-Density Lipoprotein Cholesterol and Plasma Lipids in Asian Patients with Hypercholesterolemia

“…In patients not previously treated with statins, there was a significant 39.9% reduction in LDL-C, which is remarkably similar to the 33 − 56.8% reported in other studies involving mainly Caucasian [14][15][16][17][18] or Japanese 19) patients. This study also shows that most (80.1%) primary and secondary prevention hypercholesterolemic statin-naive patients were able to achieve their therapeutic LDL-C goals with the 10 mg starting dose of rosuvastatin.…”

Effect of Rosuvastatin on ROCK Activity, Endothelial Function, and Inflammation in Asian Patients with Atherosclerosis

“…Reduction in triglycerides and increase in HDL-C were observed at both dose levels, with no dose-response effect being observed. Our results are consistent with previously reported for rosuvastatin treatment (18,19). Treatment with rosuvastatin 40 mg/day produced greater improvement in LDL-C and total cholesterol than rosuvastatin 10 mg/day; however, as expected, both treatments had equal beneficial effects for HDL-C and triglycerides.…”

A Randomized Controlled Study to Compare the Effects of Rosuvastatin 5mg and Atorvastatin10mg on the Plasma Lipid Profile in Japanese Patients with Hypercholesterolemia (ASTRO-2)

“…11,12) In JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) for men and women with normal LDL-C level (< 130 mg / dL) and elevated high-sensitivity C-reactive protein levels (≥ 0.2 mg / dL), rosuvastatin reduced cardiovascular / cerebrovascular events. 13) However, there are few data on the efficacy and safety of rosuvastatin in Japanese patients, [14][15][16] because the application for approval of the drug was based on overseas data extrapolated to Japanese. A pharmacokinetic study conducted in Japan showed that the blood concentration of the drug in Japanese patients was almost twice that in Caucasians, based on which the initial dose for Japanese patients was set at 2.5 mg / day, half of the dose used in the United States.…”