ONCE-DAILY PRAVASTATIN IN PATIENTS WITH PRIMARY HYPERCHOLESTEROLEMIA - A DOSE-RESPONSE STUDY

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 less-than-or-equal-to .001 vs. baseline and placebo) and reductions in total cholesterol of 14.3 to 25.1% (p less-than-or-equal-to .01 to p less-than-or-equal-to .001 vs. placebo and p less-than-or-equal-to .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.