Treatment of primary hypercholesterolaemia. Short-term efficacy and safety of increasing doses of simvastatin and pravastatin: a double-blind comparative study.

Abstract

OBJECTIVES: To compare the efficacy and safety of increasing doses (0, 10, 20 and 40 mg day-1, each dose for 6 weeks) of the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, simvastatin and pravastatin, in the treatment of primary hypercholesterolaemia. DESIGN: Randomized, double-blind study with two parallel groups. SETTING: Two specialist lipid clinics in the Netherlands. SUBJECTS: Forty-eight patients aged 25-66 years with primary hypercholesterolaemia (mean serum cholesterol 10.2 mmol-1). MAIN OUTCOME MEASURES: Total serum cholesterol, triglycerides, lipoproteins, apolipoproteins A-I and B, laboratory safety parameters and sleep questionnaires. RESULTS: Both drugs induced a dose-dependent reduction in the mean total and low-density lipoprotein cholesterol concentration (P < 0.001); low-density lipoprotein cholesterol decreased from 32 to 43% by simvastatin and from 23 to 33% by pravastatin. There was an overall difference in the mean relative change from baseline in favour of simvastatin (total cholesterol, P < 0.01; LDL cholesterol P < 0.001). Both drugs reduced serum triglycerides by 10-15%. The changes in apolipoprotein B and the differences in efficacy between the two drugs paralleled those of total and low-density lipoprotein cholesterol. Adverse experiences were mild and did not differ between treatment groups; in each group, one subject discontinued medication because of complaints of dizziness. Sleep questionnaires revealed different degrees of sleep problems, unaffected by active treatment. CONCLUSIONS: Simvastatin appeared to be more potent than pravastatin in lowering total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B, whereas both drugs had the same short-term safety profile.