PRINCESA: La prevención de eventos isquémicos en el tratamiento precoz de la cerivastatina

Statin therapy is well established for the long-term secondary prevention of coronary artery disease. Recent studies have focused on how early statin therapy should be instituted in acute myocardial infarction (AMI) patients and whether aggressive treatment is superior to moderate treatment. The definition of early statin treatment has varied in the different large-scale trials. Aim: The Prevention of Ischemic Events by Early Treatment of Cerivastatin (PRINCESS) study assessed whether very early statin treatment (< 48 hours from symptom onset) reduced the rates of death, recurrent infarction, and recurrent ischemia in AMI patients. STUDY DESIGN: PRINCESS was a multicenter study that assessed the effects of cerivastatin in AMI patients, regardless of baseline LDL-cholesterol levels. Patients were randomized to either cerivastatin (0.4 mg/day) (n = 1795) or placebo (n = 1810) for 3 months. After this period, placebo patients were crossed over to open-label cerivastatin and patients initially randomized to cerivastatin remained on the drug (up-titration was permitted). PRIMARY ENDPOINT: A composite of reduction in cardiovascular death, nonfatal MI, nonfatal stroke, hospitalization for unstable angina, and hospitalization for heart failure. SECONDARY ENDPOINTS: Recurrent coronary ischemia, reinfarction, and unstable angina; Overall mortality; Recurrent MI; Lipid profile changes. INCLUSION CRITERIA: Patients with AMI; Symptom onset < 6 hours; Elevated biomarkers; Electrocardiographic evidence of ST-segment elevation and/or ST-segment depression. All AMI therapies permitted, including: Aspirin and thrombolytic therapy within 6 hours; Ability to perform intervention within 12 hours of symptom onset; RESULTS: The study was prematurely stopped in August 2001 when Bayer, the drug's manufacturer, withdrew cerivastatin from the worldwide market. At that time, the study's steering committee elected to move all endpoints to 4.5 months; results were based on an intention-to-treat analysis. Baseline characteristics, typical of other populations studied in AMI trials, were well balanced between the placebo and cerivastatin groups. CONCLUSIONS: The 2 groups did not differ with regard to the primary composite endpoint or overall rates of mortality and reinfarction. Patients randomized to early statin treatment experienced fewer recurrent ischemic events by 4.5 months, mainly driven by a reduction in acute coronary syndrome and less need for subsequent percutaneous coronary intervention. The premature interruption of this study limits the power of these observations. COMMENTS: This study provides further evidence that very early initiation of statin therapy is safe and may have a potential benefit in the reduction of ischemic events in AMI patients. Despite the fact that the study was prematurely stopped and the fact that the primary endpoint of the study was not achieved, it provides substantiation that statins should be initiated as early as possible in ACS patients regardless of their lipid profile.