JAMA 2001;285:1711-18.Background Statin therapy had been shown to improve blood cholesterol and improve long-term outcomes in patients with stable coronary artery disease with significant effects evident after 2 years of treatment. These early trials excluded patients with recent acute coronary syndromes and thus, the possibility of early benefit from statin therapy in this patient population was untested. But, patients with ACS are the most vulnerable to experiencing recurrent events in the early period following an initial event and certain physiologic effects of statins were theorized to be beneficial during this period. These effects included improvement in endothelial function, decreased platelet aggregation and thrombus deposition, and reduced vascular inflammation. The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study sought to test the hypothesis that early treatment with high dose atorvastatin in patients with unstable angina or non-Q-wave AMI would reduce early ischemic events and death.Cardiology Trial’s Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients Eligible patients were ≥18 years of age of experienced unstable angina or non-Q-wave AMI within the 24-hour period before hospitalization. The definition of unstable angina was strictly applied and in contemporary practice, all would meet criteria for NSTEMI. Patients were excluded for the following reasons: serum cholesterol >270 mg/dl but there was no lower limit; if coronary revascularization was planned or anticipated at the time of screening; evidence of Q-wave AMI within preceding 4 weeks; CABG surgery within the preceding 3 months; PCI within the preceding 6 months; left bundle branch block or paced rhythm; severe CHF; concurrent treatment with other lipid-lowering agents, vitamin E, drugs associated with rhabdomyolysis in combination with statins; severe anemia; renal failure requiring dialysis; hepatic dysfunction (ALT >2 ULN); insulin-dependent diabetes; pregnancy or lactation.Baseline characteristics The average age of patients was 65 years and two-thirds were men; 86% were white. Approximately one quarter of patients had a prior MI, 23% had non-insulin-dependent diabetes and 55% had hypertension. The average time to randomization from hospital admission was about 2.5 days. The inclusion event was unstable angina in 46% and non-Q-wave AMI in the remainder. Non-cholesterol lowering cardiac medicines were similar prior to, during and following the hospitalization index event.Procedures Between 24 and 96 hours after hospital admission, patients received either atorvastatin 80 mg per day or matching placebo for 16 weeks. Treating physicians were instructed not measure serum lipid levels in the local hospital laboratory during the study period. All patients received instruction and counseling on a low cholesterol diet. Patients were seen in follow-up 2, 6, and 16 weeks after initiation of therapy. Laboratory testing was performed centrally at baseline and at 6 and 16 weeks.Endpoints The primary endpoint was a composite of all-cause death, nonfatal MI, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence requiring emergency hospitalization. The recurrent ischemia endpoint required both exacerbation of the patient’s usual symptoms and new objective evidence of ischemia with definite change from a comparison study performed after the index ischemic event. Secondary endpoints were occurrence of each component of the primary composite endpoint as well as nonfatal stroke; new or worsening heart failure requiring hospitalization, worsening angina requiring hospitalization but without objective evidence of ischemia, coronary revascularization, time to first occurrence of any primary or secondary endpoint, and percentage changes in blood lipid levels from baseline to 16 weeks.An initial sample size r