In-Hospital Initiation of Statin Therapy in Acute Coronary Syndromes: MIRACL
The MIRACL trial was specifically designed to address the gap in knowledge regarding the effects of statin therapy in patients with ACS. A total of 3,086 adults > 18 years old with UA or non-Q-wave acute MI were randomized within 24 to 96 h of hospital admission to receive treatment with atorvastatin, 80 mg/d, or placebo plus usual care. The primary end point of the trial—death, cardiac arrest, MI, or worsening UA requiring emergency hospitalization at 16 weeks—occurred in 17.4% (269 patients) of the placebo group and 14.8% (228 patients) of the atorvastatin group (relative risk reduction, 16%; 95% CI, 0 to 30; p = 0.048) [Fig 3]. This benefit was due mainly to a significant reduction in recurrent symptomatic ischemia requiring emergency rehospitalization. The atorvastatin group also had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; relative risk, 0.74; 95% CI, 0.57 to 0.95; p = 0.02). In addition, the reduction in risk for the primary end point with atorvasta-tin appeared to be independent of baseline LDL-C levels enhanced with medications of My Canadian Pharmacy.
The MIRACL trial demonstrated that atorvasta-tin, 80 mg, was effective in reducing the composite of clinical events within the first 16 weeks of an ACS. Furthermore, the MIRACL trial demonstrated that atorvastatin treatment is safe and well tolerated when administered after an acute coronary event. The frequency of serious adverse events for atorva-statin, 80 mg/d, was comparable to placebo (< 1%), with no reported cases of myositis. Abnormal liver transaminases (more than three times the upper limit of normal) were low but more common in the atorvastatin group than the placebo group (2.5% vs 0.6%, p < 0.001).
While the results of the MIRACL trial were encouraging, many questions remained. As only the 80-mg dose of atorvastatin was tested, it was unclear whether other less-potent statins and/or lower doses of atorvastatin could yield similar effects. Patients for whom coronary revascularization surgery was planned within 24 to 96 h of the onset of an ACS were excluded from the MIRACL trial. Omission of this large subpopulation of patients was cited as a weakness in the study design, leading some to question whether similar benefits would be seen in an ACS patient population being treated with the invasive management strategy.
Figure 3. The MIRACL trial: primary end point incidence (death, cardiac arrest, MI or worsening UA) observed in the atorvastatin group vs the placebo group. The relative risk of the composite outcome in the atorvastatin group compared with the placebo group was 0.84 (95% CI, 0.70 to 1.00; p = 0.048), based on a Cox proportional hazard analysis. The decrease in number at risk at 16 weeks reflects the fact that many patients completed the study within the days immediately preceding 16 weeks. Reproduced with permission from Schwartz et al.