Efficacy and safety of pravastatin in patients with primary hypercholesterolemia. I. A dose-response study

Donald B. Hunninghake, Robert H. Knopp, Gustav Schonfeld, Anne C. Goldberg, W. Virgil Brown, Ernst J. Schaefer, Simeon Margolis, Adrian S. Dobs, Margot J. Mellies, William Insull, Evan A. Stein

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


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 <= 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 <= 0.001). Triglycerides decreased by as much as 15.4% (P <= 0.001) and high-density lipoprotein (HDL) cholesterol increased approximately 7% (P <= 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.

Original languageEnglish (US)
Pages (from-to)81-89
Number of pages9
Issue number1
StatePublished - Nov 1990


  • Clinical trial
  • Dose-response
  • HMG-CoA reductase inhibitors
  • Pravastatin
  • Safety

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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