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.