Treating hypercholesterolaemia with HMG CoA reductase inhibitors: a direct comparison of simvastatin and pravastatin

Abstract

Simvastatin and pravastatin are both competitive inhibitors of the rate limiting enzyme for cholesterol biosynthesis (HMG CoA) reductase, but data from individual clinical trials suggest significant differences in potency for cholesterol reduction between the two drugs. To assess any differences in efficacy and safety between simvastatin and pravastatin in a direct, comparative study. A double-blind, double-dummy, randomised study design was used, involving 48 patients with primary hypercholesterolaemia. Following a 6 week placebo baseline period, patients were randomly allocated to treatment with either simvastatin or pravastatin, commencing at a dose of 10 mg daily. The dose levels were titrated up to the recommended maximum effective dose of 40 mg daily at 6 weekly intervals if LDL cholesterol levels remained > or = 3.4 mmol/L. After 18 weeks of therapy, all patients were transferred to simvastatin therapy for a further 6 weeks, continuing at their week 18 dose level. Patients complied with a standard lipid lowering diet (containing < 30% of energy as total fat) throughout the study period. Over the 18 week direct comparison of the two drugs, there was a significant difference (p < 0.001) in response between simvastatin and pravastatin for reduction in levels of total cholesterol (32% vs 21% respectively), LDL cholesterol (38% vs 27%) and apolipoprotein B levels (34% vs 23%). No significant difference in drug effect was seen for the small reduction in levels of apolipoprotein AI (5% vs 6% respectively), nor for the increased levels of apolipoprotein AII (14% vs 11%) and HDL cholesterol (11% vs 7%). Lp(a) levels remained unchanged. When pravastatin was replaced with simvastatin for the final 6 weeks of the study in the 23 patients initially randomised to pravastatin, there were further reductions (p < 0.01) in total and LDL cholesterol, and apolipoprotein B. These results establish the advantage of simvastatin over pravastatin in terms of efficacy, for the treatment of primary hypercholesterolaemia.