TREATING HYPERCHOLESTEROLEMIA WITH HMG-COA REDUCTASE INHIBITORS - A DIRECT COMPARISON OF SIMVASTATIN AND PRAVASTATIN

Background: Simvastatin and pravastatin are both competitive inhibitor s of the rate limiting enzyme for cholesterol biosynthesis (HMG CoA) r eductase, but data from individual clinical trials suggest significant differences in potency for cholesterol reduction between the two drug s. Aim: To assess any differences in efficacy and safety between simva statin and pravastatin in a direct, comparative study. Methods: A doub le-blind, double-dummy, randomised study design was used, involving 48 patients with primary hypercholesterolaemia. Following a 6 week place bo baseline period, patients were randomly allocated to treatment with either simvastatin or pravastatin, commencing at a dose of 10 mg dail y. The dose levels were titrated up to the recommended maximum effecti ve dose of 40 mg daily at 6 weekly intervals if LDL cholesterol levels remained greater-than-or-equal-to 3.4 mmol/L. After 18 weeks of thera py, all patients were transferred to simvastatin therapy for a further 6 weeks, continuing at their week 18 dose level. Patients complied wi th a standard lipid lowering diet (containing <30% of energy as total fat) throughout the study period. Results: Over the 18-week direct com parison of the two drugs, there was a significant difference (p<0.001) in response between simvastatin and pravastatin for reduction in leve ls of total cholesterol (32%vs21% respectively), LDL cholesterol (38%v s27%) and apolipoprotein B levels (34%vs23%). No significant differenc e in drug effect was seen for the small reduction in levels of apolipo protein AI (5%vs6% respectively), nor for the increased levels of apol ipoprotein AII (14%vs11%) and HDL cholesterol (11%vs7%). Lp(a) levels remained unchanged. When pravastatin was replaced with simvastatin for the final 6 weeks of the study in the 23 patients initially randomise d to pravastatin, there were further reductions (p < 0.01) in total an d LDL cholesterol, and apolipoprotein B. These results establish the a dvantage of simvastatin over pravastatin in terms of efficacy, for the treatment of primary hypercholesterolaemia.