Efficacy and safety of pravastatin in patients with primary hypercholesterolemia. I. A dose-response study.
This multicenter, double-blind, placebo-controlled, dose-response study was conducted in patients with primary hypercholesterolemia to examine the effects of pravastatin, a selective inhibitor of HMG-CoA reductase, on plasma lipids and lipoproteins. A total of 306 patients on cholesterol-lowering diets received twice daily doses of 5 mg, 10 mg, 20 mg pravastatin, or placebo for 12 weeks. Marked reductions in low density lipoprotein (LDL) cholesterol and total cholesterol were observed after 1 week of treatment; maximum lipid-lowering effects occurred at 4 weeks and were sustained for the duration of the trial. At week 12, pravastatin treatment resulted in dose-dependent mean reductions from baseline in LDL cholesterol of 17.5%, 22.9%, and 30.8% for the 3 doses tested (P less than or equal to 0001 compared with baseline and placebo). The reduction in LDL cholesterol was log-linear with respect to dose; each doubling of dose reduced LDL cholesterol an additional 6.5%. Dose-dependent reductions in total cholesterol from 12.9% to 23.3% also occurred (P less than or equal to 0.001). Triglycerides decreased by as 15.4% (P less than or equal to 0.001) and high-density lipoprotein (HDL) cholesterol increased approximately 7% (P less than or equal to 0.01), but these effects were not dose-dependent. No patient receiving pravastatin was discontinued during the 12-week trial. Transient episodes of rash and headache occurred. Slight increases in mean serum levels of ASAT and ALAT occurred, and 2% of both placebo- and pravastatin-treated patients reported myalgia although there was no clinically significant elevation of creatine kinase. These data indicate that pravastatin favorably affects all lipid parameters and is well tolerated.
Hunninghake
D B
DB
University of Minnesota School of Medicine, Minneapolis.
Knopp
R H
RH
Schonfeld
G
G
Goldberg
A C
AC
Brown
W V
WV
Schaefer
E J
EJ
Margolis
S
S
Dobs
A S
AS
Mellies
M J
MJ
Insull
W
W
D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000009:adverse effects / Q000627:therapeutic use*; D017035:Pravastatin; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009281:Naphthalenes; D014280:Triglycerides; D002784:Cholesterol; D017035:Pravastatin