EFFECT OF PRAVASTATIN IN THE PREVENTION OF CORONARY HEART-DISEASE IN PATIENTS WITH PRIMARY HYPERCHOLESTEROLEMIA

Ninety-two patients (51 men and 41 women; mean age, 48 +/- 7 years) were enrolled in a study to assess the effect of pravastatin on the 10-year probability of myocardial infarction (MI). All patients had primary hypercholesterolemia but were free of coronary heart disease (CHD) at baseline. They were placed on a hypolipidemic diet and received a placebo for 3 months. At the end of the 3-month period (month 0), the placebo was replaced by pravastatin 20 mg once daily at bedtime. If total cholesterol was not reduced by at least 15% at 3 months, the dose was increased to 40 mg once daily. The patients were treated with pravastatin for 6 months (average dose, 23 mg). At months -3, 0, 1, 3, and 6, the 10-year probability of MI was calculated by using a computer program that we designed to coevaluate 10 independent CHD risk factors. The mean 10-year probability of MI for all 92 patients at month -3 was 24.5%. The hypolipidemic diet and placebo administration had little effect on MI risk, with the 10-year probability remaining at 23.4% at month 0. This percentage was significantly higher than that expected (10.3%; P < 0.001) for this specific group of patients (the expected value was calculated from an age- and sex-matched group from the general population). At treatment month 1, the 10-year probability for MI was 18.8% (Delta m = -19.6%; P < 0.05 vs month 0), while at months 3 and 6 it was estimated at 13.6% and 11.3%, respectively (Delta m = -41.9% and Delta m = -51.7%; P < 0.001 vs month 0 for both estimates). The value at month 6 was not significantly different from the expected estimates. This effect of pravastatin was attributed to a significant reduction in low-density lipoprotein cholesterol levels and a minor increase in high-density lipoprotein cholesterol levels, without adversely affecting other CHD risk factors. Myopathy, significant liver dysfunction, ocular problems, and sleep disorders were not detected during the 6-month treatment period. We conclude that pravastatin is an effective and safe hypolipidemic agent that significantly reduces MI risk in patients with primary hypercholesterolemia.