Pravastatin once daily in hypercholesterolaemia: a U.K. study

The aim of this study was to evaluate the efficacy and safety of pravastatin, a hydrophilic HMG-CoA reductase inhibitor, versus placebo in combination with dietary, smoking and lifestyle advice in patients with primary mild to moderate hypercholesterolaemia and additional risk factors for coronary heart disease. A double-blind, randomized, parallel, placebo-controlled multicentre outpatient study was used. The study group comprised 154 patients from 13 U.K. centres, aged 22–76 years, with primary hypercholesterolaemia (total cholesterol 5.2–7.8 mmol/l) after diet and at least two additional coronary risk factors. Patients received either pravastatin 20 mg or placebo once daily in addition to continued dietary advice for 26 weeks. If total cholesterol concentration was not reduced to less than 5.2 mmol/l or 15% from baseline, the dose of pravastatin was doubled to 40 mg. The main outcome measures as regards efficacy were: total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides and as regards safety were: adverse events, ophthalmology, serum hepatic transferases and creatine kinase. In 79 pravastatin-treated patients, when compared with 75 placebo-treated patients, total cholesterol and LDL-cholesterol decreased significantly by 21% (P<0.001) and 33% (P<0.001), respectively, in pravastatin-treated patients when compared with placebo (2 and 8% reductions, respectively). Seventy pravastatin and 67 placebo patients remained in the study after 13 weeks and 68 and 61 patients, respectively, completed the 26-week study treatment period. In both treatment groups there was a non-significant increase in HDL-cholesterol. Of patients who received pravastatin, 81% achieved target levels by week 26 as compared with only 7% who received placebo. Twelve pravastatin- and 58 placebo-treated patients required double doses. There was a similar incidence of adverse events in each treatment group. The only clinically significant finding was a dose-related increase in the serum aminotransferases in patients taking pravastatin, none of whom were shown to have clinical signs or symptoms of liver disease. During the course of this 26-week study, pravastatin was shown to be effective and well tolerated in patients with mild to moderate primary hypercholesterolaemia and additional risk factors.