Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes - The MIRACL study: A randomized controlled trial

Context Patients experience the highest rate of death and recurrent ischemi c events during the early period after an acute coronary syndrome, but it i s not known whether early initiation of treatment with a statin can reduce the occurrence of these early events. Objective To determine whether treatment with atorvastatin, 80 mg/d, initia ted 24 to 96 hours after an acute coronary syndrome, reduces death and nonf atal ischemic events. Design and Setting A randomized, double-blind trial conducted from May 1997 to September 1999, with follow-up through 16 weeks at 122 clinical centers in Europe, North America, South Africa, and Australasia. Patients A total of 3086 adults aged 18 years or older with unstable angina or non-Q-wave acute myocardial infarction. Interventions Patients were stratified by center and randomly assigned to r eceive treatment with atorvastatin (80 mg/d) or matching placebo between 24 and 96 hours after hospital admission. Main Outcome Measures Primary end point event defined as death, nonfatal ac ute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emerg ency rehospitalization. Results A primary end point event occurred in 228 patients (14.8%) in the a torvastatin group and 269 patients (17.4%) in the placebo group (relative r isk [RR], 0.84; 95% confidence interval [CI], 0.70-1.00; P = .048). There w ere no significant differences in risk of death, nonfatal myocardial infarc tion, or cardiac arrest between the atorvastatin group and the placebo grou p, although the atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; RR, 0.74; 95% CI, 0.57-0.95; P = .02). Likewise, there were no signi ficant differences between the atorvastatin group and the placebo group in the incidence of secondary outcomes of coronary revascularization procedure s, worsening heart failure, or worsening angina, although there were fewer strokes in the atorvastatin group than in the placebo group (12 vs 24 event s; P = .045). In the atorvastatin group, mean low-density lipoprotein chole sterol level declined from 124 mg/dL (3.2 mmol/L) to 72 mg/dL (1.9 mmol/L). Abnormal liver transaminases (>3 times upper limit of normal) were more co mmon in the atorvastatin group than in the placebo group (2.5% vs 0.6%; P < .001). Conclusion For patients with acute coronary syndrome, lipid-lowering therap y with atorvastatin, 80 mg/d, reduces recurrent ischemic events in the firs t 16 weeks, mostly recurrent symptomatic ischemia requiring rehospitalizati on.