MIRACL: The Effect of Statin Treatment in ACS

Results of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study, first released at the American Heart Association meeting in November, were published in April (JAMA. 2001;285:1711–1718).
   The trial investigators' aim was to determine whether 80 mg/d of atorvastatin initiated 24 to 96 hours post acute coronary syndrome (ACS) would reduce nonfatal ischemic events and death. The study included 3,086 adult patients who had experienced unstable angina or non–Q-wave acute myocardial infarction (MI). They were randomly assigned to receive the atorvastatin dosage or matching placebo, with follow-up at 2, 6, and 16 weeks.
   The primary combined end point included death, recurrent nonfatal MI, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence requiring emergency rehospitalization. In the atorvastatin group, 14.8% had a primary end-point event; in the placebo group, 17.4% had one (RR, 0.84; 95% CI, 0.70–1.00; P=.048). The benefit seemed mainly to arise from fewer presentations of recurrent ischemia.
   As for secondary end points, there was a significant reduction in fatal or nonfatal stroke among the atorvastatin group—12 patients compared with 24 patients in the placebo group (RR, 0.50; 95% CI, 0.26–0.99; P=.045).
   In an accompanying editorial (JAMA. 2001;285:1758–1760.), there was a call for more precise clinical evaluation of the outcomes—both positive and negative. Also questioned was why atorvastatin 80 mg was used in the study instead of the usual dose of 10 mg, especially since the participants had average, not severe, LDL-C levels. While confident of the results and the methods used in the trial (explaining that they "chose the 80-mg dose to produce a large average reduction in serum cholesterol levels"), the MIRACL investigators admit that there is still a need for further trials regarding statin use in ACS.
   Although short-term treatment with atorvastatin did not reduce "harder" clinical end points, the reduction in risk for recurrent ischemia makes it comparable to other treatment strategies. Hence, the investigators feel that atorvastatin treatment should become part of the initial management of these patients, regardless of cholesterol levels after an acute event.
   At randomization, the two groups of patients had almost identical mean serum lipid levels: LDL-C 124 mg/dL; TGs 184 mg/dL; HDL-C 46 mg/dL. At the end of the study, mean lipid levels in the atorvastatin group had declined: LDL-C by 40% (to 72 mg/dL) and TGs by 16% (to 139 mg/dL). In the placebo group, mean LDL-C increased by 12% (to 135 mg/dL) and mean TG levels increased 9% (to 187 mg/dL). Only minor changes were observed in both groups' HDL-C.