Once‐daily pravastatin in patients with primary hypercholesterolemia: A dose‐response study

Abstract

This multicenter, double‐blind, placebo‐controlled study was conducted to evaluate dose‐response effects and safety of once‐daily administration of pravastatin, a new inhibitor of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase. Pravastatin 5, 10, 20, 40 mg or placebo was administered at bedtime to 150 patients with primary hypercholesterolemia inadequately controlled on a low‐fat, low‐cholesterol (AHA Phase I) diet. After 8 weeks of treatment, pravastatin produced dose‐dependent reductions in low‐density lipoprotein (LDL) cholesterol of 19.2 to 34.1% (p⩽.001 vs. baseline and placebo) and reductions in total cholesterol of 14.3 to 25.1% (p⩽.01 to p⩽.001 vs. placebo and p⩽.001 vs. baseline). The relationship between the log_e dose of pravastatin and decrease in LDL cholesterol was linear (p<0.002). High‐density‐lipoprotein cholesterol increased up to 11.7% and triglycerides decreased by as much as 23.9%. Pravastatin was well tolerated; no patient withdrew from the study as a consequence of treatment‐related adverse events. Despite its relatively short serum half‐life of approximately 2 h, once‐daily administration of pravastatin provides a safe and effective means of reducing elevated LDL and total cholesterol.