The PROVE IT-TIMI 22 trial40 has extended the findings of the MIRACL trial, while also demonstrating the greater benefits of intensive lipid-lowering therapy with atorvastatin, 80 mg, compared to conventional lipid-lowering therapy with pravastatin, 40 mg. In total, 4,162 men and women aged > 18 years who had been hospitalized for an ACS within the preceding 10 days (patients had to be in stable condition and were enrolled after a percutaneous revascularization procedure if one was planned) were randomized to either standard therapy (pravastatin, 40 mg/d) or intensive therapy (atorvastatin, 80 mg/d) for a mean follow-up period of 2 years. The combined primary end point was death from any cause, MI, documented UA requiring hospitalization, stroke, and revascularization surgery performed after 30 days from randomization. At 2 years, primary end point event rates were 26.3% in the pravastatin 40 mg/d group and 22.4% in the atorvastatin 80 mg/d group, representing a 16% relative reduction in favor of atorvastatin (absolute risk reduction, 3.9%; 95% CI, 5 to 26; p = 0.005) [Fig 4]
. Among the individual components of the primary end point, there was a consistent pattern of benefit favoring high-dose atorvastatin over standard-dose pravastatin, which included a significant 14% reduction in the need for revascularization (p = 0.04), a 29% reduction in the risk of recurrent UA (p = 0.02), and trends for reductions in the rates of all-cause mortality (28%, p = 0.07) and of death or MI (18%, p = 0.06). This benefit was seen on top of a background of evidence-based ACS management. Three fourths of the patients were treated with an early invasive strategy, and the majority of patients were treated with multiple medications for secondary prevention, including antiplatelet therapy, β-blockers, and ACE inhibitors.