Effect of rosuvastatin on low-density lipoprotein cholesterol in patients with hypercholesterolemia.
Rosuvastatin is a new, synthetic, orally active statin, with marked low-density lipoprotein (LDL) cholesterol-lowering activity. We conducted 2 dose-ranging studies. In the first study, after a 6-week dietary run-in, 142 moderately hypercholesterolemic patients were randomized equally to receive double-blind placebo or rosuvastatin 1, 2.5, 5, 10, 20, or 40 mg or open-label atorvastatin 10 or 80 mg once daily for 6 weeks; in the second study, conducted to extend the rosuvastatin dose range, 64 patients were randomized to double-blind, once-daily placebo or rosuvastatin 40 or 80 mg (1:1:2 ratio) for 6 weeks. Data from both studies were combined for analysis of lipid effects. No statistical comparison of atorvastatin arms with placebo or rosuvastatin was performed. Rosuvastatin was associated with highly significant dose-dependent reductions in LDL cholesterol compared with placebo (p <0.001); decreases ranged from 34% (1 mg) to 65% (80 mg). Linear regression analysis indicated an additional 4.5% LDL cholesterol reduction for each doubling of the rosuvastatin dose. Across the dose range, approximately 90% of LDL cholesterol reduction occurred within the first 2 weeks of treatment. Significant, dose-dependent reductions in total cholesterol and apolipoprotein B with rosuvastatin were also observed (p <0.001). High-density lipoprotein cholesterol increases and triglyceride reductions were consistently observed and statistically significant at some dose levels. All lipid ratios were significantly reduced at all rosuvastatin dose levels (p <0.001). Adverse events were similar across placebo and active treatments. No significant increases in alanine aminotransferase or creatine kinase were seen in any patient. Over 6 weeks, rosuvastatin produced large, rapid, dose-dependent LDL cholesterol reductions and was well tolerated in hypercholesterolemic patients.
Olsson
A G
AG
Department of Medicine and Care, University Hospital, Linköping, Sweden. andol@kfc.liu.se
Pears
J
J
McKellar
J
J
Mizan
J
J
Raza
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000032:analysis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D006937:Hypercholesterolemia / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines; D011758:Pyrroles / Q000008:administration & dosage*; D012016:Reference Values; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D006538:Heptanoic Acids; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin