Comparison of Intensive and Moderate Lipid Lowering With Statins After Acute Coronary Symptoms

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.