Statins, given to lower blood cholesterol, clearly reduce the risk of cardiovascular events and deaths in patients with and also those without a history of coronary artery disease. Previous trials have reported a 25% to 35% reduction in low-density lipoprotein (LDL) cholesterol. Current guidelines propose a target concentration of less than 100 mg/dL. The Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial compared standard treatment (40 mg pravastatin daily) with more intensive treatment that lowers the LDL cholesterol to approximately 70 mg/dL. Participants were 4162 clinically stable patients aged 18 and older who had been hospitalized for an acute coronary syndrome (acute myocardial infarction with or without ST-segment elevation, high-risk unstable angina) in the past 10 days. Total blood cholesterol was no greater than 240 mg/dL. Using a double-blind design, the patients were randomly assigned to receive either 40 mg pravastatin or 80 mg atorvastatin daily. Dietary counseling was provided, and patients were seen every 4 months (mean follow up, 24 months). The primary outcome was the interval between randomization and death from any cause, myocardial infarction (MI), severe unstable angina, revascularization, or stroke. The 2 groups were well matched except for more peripheral artery disease in the pravastatin group. The most common index events were unstable angina and MI with or without ST-segment elevation. More than two thirds of patients had a percutaneous coronary artery intervention before randomization. After 30 days, the median LDL cholesterol in patients receiving a statin for the first time declined by 22% and 51%, respectively, in the pravastatin and atorvastatin groups. Rates of the primary end point at 2 years were 26% in the pravastatin group and 22.4% with high-dose atorvastatin therapy. A 16% reduction in the hazard ratio favored atorvastatin. The benefit gained from high-dose therapy was evident at 30 days and persisted over time. The risk of a secondary end point (coronary death, MI, revascularization) was reduced by 14% in patients given atorvastatin (17.7% vs. 22.3% in the pravastatin group). Comparable efficacy was found for men and women, for patients with MI, and for diabetics. A significant increase in serum alanine aminotransferase was noted in 1.1% of the pravastatin group and 3.3% of those given atorvastatin. Intensive statin therapy provides more protection against death or major cardiovascular events than does standard treatment in patients with a recent acute coronary syndrome. It could be that the target LDL cholesterol in these patients should be lower than that currently recommended.
Cannon et al. (2004) studied this question.