Rationale and design of a secondary prevention trial of lowering normal plasma cholesterol levels after acute myocardial infarction: the Cholesterol and Recurrent Events trial (CARE).

Recent clinical trials of primary and secondary prevention of cardiovascular disease have demonstrated that lowering plasma cholesterol decreases the incidence of coronary heart disease in patients with elevated plasma cholesterol. However, it is not known whether patients with established coronary artery disease and normal plasma cholesterol can be benefited. Several previous prevention trials reviewed in this report found that patients who had plasma cholesterol levels at baseline in the upper portion of the eligibility range (e.g., greater than 240 mg/dl) received greater benefit from hypolipidemic diet or drug therapy than patients who had lower plasma cholesterol levels at baseline. The recent availability of drugs that are more potent and less prone to cause adverse reactions than previous regimens permits this important question to be addressed. The Cholesterol and Recurrent Events trial is testing whether pravastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, will decrease the sum of fatal coronary heart disease and nonfatal myocardial infarction (MI) in patients who have recovered from a MI and who have normal total cholesterol levels. Fatal cardiovascular disease and total mortality are important secondary end points. The trial is enrolling 4,000 men and women from 80 centers throughout North America, age 21 to 75 years, who have survived MI for 3 to 20 months, who have plasma total cholesterol less than 240 mg/dl (6.2 mmol/liter) and low-density cholesterol of 115 to 174 mg/dl (3.0 to 4.5 mmol/liter), and who are representative of the general population of patients with MI. Patients are randomized to either active or inactive drug therapy. Active therapy consists of pravastatin, 40 mg/day, designed to achieve an average decrease in low-density lipoprotein cholesterol of approximately 30%, and an increase in high-density lipoprotein of 5%. The average duration of follow-up will be greater than or equal to 5 years. To protect against a lower than expected rate of recurrent events, the trial will be continued until a predetermined fixed number of coronary heart disease events occurs in the entire cohort so that the original sensitivity of the trial will be maintained.