The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Trial: Effects of Intensive Atorvastatin Treatment on Early Recurrent Events After an Acute Coronary Syndrome
Background: Previous trials have demonstrated that treatment with conventional doses of statins, initiated in patients with stable coronary heart disease, reduces death and non-fatal ischemic events over periods of years. The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial tested the hypothesis that intensive treatment with atorvastatin, initiated immediately after an acute coronary syndrome, reduces death and non-fatal ischemic events in the ensuing 16 weeks. Methods: We conducted a randomized, double-blind trial comparing atorvastatin (80 mg daily) with placebo in 3086 patients with unstable angina or non-Q-wave acute myocardial infarction. Treatment was initiated 24 to 96 hours after hospitalization and continued for 16 weeks. The primary combined endpoint was death, non-fatal acute myocardial infarction, cardiac arrest with resuscitation, or worsening angina with new objective evidence of ischemia requiring emergency rehospitalization, analyzed by time to first event. Secondary endpoints included the components of the primary endpoint as well as stroke, coronary revascularization, worsening congestive heart failure, and worsening angina without new objective evidence of ischemia. Results: A primary endpoint event occurred in 228 patients in the atorvastatin group (14.8%) and 269 patients in the placebo group (17.4%) (relative risk, 0.84; 95% confidence interval, 0.70 to 1.00; P=0.048). The greatest effect of atorvastatin was on worsening angina with new objective evidence of ischemia requiring emergency rehospitalization (relative risk, 0.74; 95% confidence interval 0.57 to 0.95; P=0.02). Death, non-fatal myocardial infarction, and cardiac arrest were less frequent in the atorvastatin group than in the placebo group, but the differences were not statistically significant. Of the other secondary endpoints, there were significantly fewer strokes in the atorvastatin group than in the placebo group (12 versus 24 events). In the atorvastatin group, mean LDL cholesterol declined from 123 to 72 mg/dl [3.2 to 1.9 mmol/l]. Abnormal liver transaminases (>3 times upper limit of normal) occurred in 2.5% and 0.6% of patients in atorvastatin and placebo groups, respectively. Conclusion: Early, intensive lipid-lowering with atorvastatin reduces recurrent ischemic events in the first 16 weeks after an acute coronary syndrome.
- Copyright © 2000 by American Heart Association