Improved outcome after acute coronary syndromes with an intensive versus standard lipid-lowering regimen: results from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial

The aim of the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial was to determine whether intensive low-density lipoprotein (LDL)-cholesterol lowering to a level of approximately 70 mg/dL (1.8 mmol/L) with atorvastatin 80 mg/day was more efficacious than standard LDL cholesterol lowering to 100 mg/dL (2.6 mmol/L) with pravastatin 40 mg/day in reducing the incidence of cardiovascular events in patients with acute coronary syndrome (ACS). In total, 4,162 men and women aged >18 years, who had been hospitalized for an ACS within the preceding 10 days, were randomized to receive either pravastatin 40 mg/day or atorvastatin 80 mg/day. The median LDL cholesterol levels achieved during follow-up were 95 mg/dL (2.5 mmol/L) in the pravastatin group and 62 mg/dL (1.6 mmol/L) in the atorvastatin group (P <0.001). Standard treatment (statin) with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (pravastatin 40 mg/day) resulted in a 22% reduction in LDL cholesterol levels at 30 days compared with a 51% reduction with intensive therapy (atorvastatin 80 mg/day). At 2 years, a relative risk reduction of 16% (95% confidence interval, 5%-26%; P = 0.005) in the primary end point rate (death, myocardial infarction, documented unstable angina requiring hospitalization, coronary revascularization, or stroke) was seen in patients receiving intensive statin treatment compared with standard statin therapy. The benefit of intensive treatment was apparent as early as 30 days and was consistent over time. The PROVE IT-TIMI 22 data indicate that patients recently hospitalized for an ACS benefit from early and continued lowering of LDL cholesterol to levels substantially below current guideline recommendations.