Effects of Atorvastatin on Early Recurrent Ischemic Events in Acute Coronary Syndromes. The MIRACL Study: A Randomized Controlled Trial - MIRACL Study

Description:

Effects of Atorvastatin on Early Recurrent Ischemic Events in Acute Coronary Syndromes. The MIRACL Study: A Randomized Controlled Trial.

Hypothesis:

To determine whether treatment with atorvastatin given in the early phase of an acute coronary syndrome reduces death and nonfatal ischemic events.

Study Design

Study Design:

Patients Enrolled: 3086
Mean Follow Up: 16 weeks
Female: 35

Primary Endpoints:

The combined incidence of death, nonfatal acute MI, cardiac arrest or hospitalization for cardiac symptoms with objective evidence for myocardial ischemia.

Drug/Procedures Used:

Multinational study in 3086 patients with unstable angina or a non-Q-wave infarction randomized to 80 mg/d atorvastatin vs. placebo with follow-up through 16 weeks.

Principal Findings:

The mean age was 65 years, 35% were women, 35% were from North America, 25% had a previous MI, 10% had a previous revascularization, 28% were smokers, 55% were hypertensive and 25% were diabetic. Concurrent medication included ASA in 91%, beta-blockers in 77% and ACE inhibitors in 49%. The mean LDL-C at entry was 124 mg/dL, triglycerides 184 mg/dL and HDL-C 46 mg/dL. At study end, the LDL-C increased to 135 mg/dL in the placebo and decreased to 72 mg/dL with atorvastatin. A primary end point event occurred in 17.4% of the placebo and 14.8% of the atorvastatin group, a relative risk (RR) of 0.84 (95% CI, 0.70-1.00, p=0.048). Of the primary end points, the sole significant benefit of treatment was a lower risk of emergency hospitalizations for symptomatic ischemia (RR 0.74, 95%CI, 0.57-0.95, p=0.02). The benefit of treatment was similar in patients whose baseline LDL-C was above or below the entry median of 121 mg/dL, and there was no association between percentage change in LDL-C and primary end point events. There was also marked reduction in nonfatal and fatal stroke rates with treatment (0.7% vs. 1.5%, RR 0.50, CI 0.26-0.99, p=0.045).

For patients with acute coronary syndrome, lipid lowering therapy with 80 mg of atorvastatin reduces recurrent ischemic events in the first 16 weeks, mostly symptomatic ischemia requiring hospitalization.

Interpretation:

Aggressive lowering of the LDL-C can was associated with a reduction in recurrent acute coronary ischemia at 16 weeks. This is consistent with improved endothelial function and possibly accelerated healing of ruptured plaque. Unfortunately the study only tested very high-dose atorvastatin and not the value of lower doses and the effect of other agents such as ACE inhibitors. The 16-week cost of treatment with atorvastatin is estimable at about $34,000 per event prevented. In an accompanying editorial, Frank Sacks observed: 1) since there was no association between outcome and baseline or on treatment LDL-C within the treatment arm, the standard 10 mg dose of atorvastatin may have been as effective; 2) the results were of borderline significance and the 11 patients lost to follow-up could have influenced the data. Nevertheless, the study lends support for statin therapy to be considered in all patients discharged from the hospital with an acute coronary syndrome including MI.

References:

1. Schwartz GG, Olsson AG, Ezekowitz MD, et al. for the Myocardial Ischemia Reduction with Aggressive Cholesterol-Lowering (MIRACL) Study Investigators. JAMA 2001;285:1711-8.

Clinical Topics: Acute Coronary Syndromes, Diabetes and Cardiometabolic Disease, Dyslipidemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: Risk, Stroke, Acute Coronary Syndrome, Follow-Up Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Coronary Disease, Lost to Follow-Up, Heptanoic Acids, Pyrroles, Triglycerides, Diabetes Mellitus


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