PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy: Thrombolysis in Myocardial Infarction-22)

18 Aug, 10

PROVE IT-TIMI 22

Objective

To determine the timing of benefit with intensive statin therapy after an acute coronary syndrome (ACS) in two time windows: an early window soon after an ACS and a late window in more stable patients

Study Design and Participants

4,162 patients who had a total cholesterol level of <240 mg/dl and who had been hospitalized for ACS within the previous 10 days were randomly assigned in a 1:1 ratio to pravastatin 40 mg or atorvastatin 80 mg daily
Patients were followed up for 18 to 36 months, with an average follow-up of 24 months

Endpoints

Primary end point was all-cause mortality, myocardial infarction (MI), unstable angina requiring rehospitalization, revascularization (if performed at least 30 days after randomization), and stroke
Composite triple end point of death, MI, or rehospitalization for recurrent ACS was determined in each group at 30 days
Composite triple and primary end points were assessed in stable patients from 6 months to the end of study, after censoring for clinical events before 6 months

Results

In comparison to pravastatin, patients receiving atorvastatin showed:

15% risk reduction in the primary end point at 15 days
28% risk reduction at 30 days in the triple end point
15% risk reduction in the primary end point from 6 months to the end of the study
28% risk reduction in the triple end point from 6 months to the end of the study
24% risk reduction in the overall occurrence of the triple end point

Figure 1. Kaplan-Meier estimates of the composite end point of death, MI, and rehospitalization with recurrent ACS

Intensive therapy lowered low-density lipoprotein cholesterol (LDL-C) and C-reactive protein (CRP) more than the standard therapy at 30 days and at four months (Table 1)

Table 1. Effect on LDL-C and CRP

Conclusions

Intensive versus standard statin therapy leads to a reduction in clinical events within 30 days after an ACS, within a time window consistent with the early pleiotropic effects seen with statins
Intensive statin therapy provides two windows of cardioprotection in patients with ACS
Treatment of patients with ACS should begin in-hospital with high-dose intensive stain therapy to achieve these early clinical benefits and should be continued long-term

J Am Coll Cardiol 2005; 46:1405-10