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) we re enrolled in a study to assess the effect of pravastatin on the 10-y ear probability of myocardial infarction (MI). All patients had primar y hypercholesterolemia but were free of coronary heart disease (CHD) a t baseline. They were placed on a hypolipidemic diet and received a pl acebo for 3 months. At the end of the 3-month period (month 0), the pl acebo was replaced by pravastatin 20 mg once daily at bedtime. If tota l cholesterol was not reduced by at least 15% at 3 months, the dose wa s increased to 40 mg once daily. The patients were treated with pravas tatin 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 pro gram that we designed to coevaluate 10 independent CHD risk factors. T he mean 10-year probability of MI for all 92 patients at month -3 was 24.5%. The hypolipidemic diet and placebo administration had little ef fect on MI risk, with the 10-year probability remaining at 23.4% at mo nth 0. This percentage was significantly higher than that expected (10 .3%; P < 0.001) for this specific group of patients (the expected valu e was calculated from an age- and sex-matched group from the general p opulation). At treatment month 1, the 10-year probability for MI was 1 8.8% (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% an d Delta m = -51.7%; P < 0.001 vs month 0 for both estimates). The valu e at month 6 was not significantly different from the expected estimat es. This effect of pravastatin was attributed to a significant reducti on in low-density lipoprotein cholesterol levels and a minor increase in high-density lipoprotein cholesterol levels, without adversely affe cting other CHD risk factors. Myopathy, significant liver dysfunction, ocular problems, and sleep disorders were not detected during the 6-m onth treatment period. We conclude that pravastatin is an effective an d safe hypolipidemic agent that significantly reduces MI risk in patie nts with primary hypercholesterolemia.