Lipitor

Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes. The MIRACL study: a randomized controlled trial. JAMA 2001; 285:1711-18.

* BACKGROUND Patients experience the highest rate of death and recurrent ischemia in the early period after the onset of acute coronary syndrome (ACS). The authors of this study hoped to determine whether treatment with a statin soon after an ACS could reduce the reoccurrence of these events.

* POPULATION STUDIED The population studied included 3086 adults 18 years or older with unstable angina or non-Q-wave acute myocardial infarction (AMI). The intervention and control groups were similar in baseline characteristics.

Patients were not included if they had experienced a Q-wave AMI, had a recent or planned coronary revascularization procedure, had severe heart failure, or had left bundle branch block. Those with a contraindication to atorvastatin or who were taking high doses of vitamin E were also excluded.

* STUDY DESIGN AND VALIDITY Using a double-blind study design with concealed allocation assignment, patients received either atorvastatin 80 mg per day or matching placebo, beginning 24 and 96 hours after hospital admission. Lipid analysis was measured at baseline, 6 weeks, and 16 weeks. All patients received counseling to promote compliance with a National Cholesterol Education Project Step I diet. The patients were evaluated at 2, 6, and 16 weeks following enrollment. They were analyzed in the groups to which they were assigned (intention-to-treat analysis). Follow-up was available for 99.6% of the subjects.

This study was well designed. The main limitations were not including a group with the most typical dose of atorvastatin (10 mg) and a relatively short follow-up period (16 weeks). Short follow-up may lead to either an underestimation or overestimation of the effect of atorvastatin.

* OUTCOMES MEASURED Primary endpoints included death, nonfatal acute MI, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization.

Secondary endpoints included nonfatal stroke, recurrent angina without objective evidence of ischemia, and coronary revascularization procedures. Subsets of the individual endpoints were also analyzed.

* RESULTS Death or recurrent ischemia or infarction occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group (P=.048; number needed to treat [NNT]=38). Analyzing subgroups of this primary endpoint, the atorvastatin group had a lower incidence symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; P=.02; NNT=46). There were no significant differences in the remaining individual primary endpoints.

Fewer patients in the atorvastatin group experienced a stroke (12 vs 24 events; P=.045; NNT=1600). No other secondary outcomes were affected by active therapy. In the atorvastatin group, mean low-density lipoprotein cholesterol level declined 40% (124 mg/dL to 72 mg/dL), while the placebo group actually increased 120/6 (124 mg/dL to 135 mg/dL). Abnormal liver transaminases ([is greater than] 3 times upper limit of normal) were more common in the atorvastatin group than in the placebo group (2.5% vs 0.6%; P=.001; number needed to harm=52).

RECOMMENDATIONS FOR CLINICAL PRACTICE

Atorvastatin 80 mg per day started within 96 hours of non-Q-wave AMI or unstable angina (ACS) reduces recurrent ischemic events requiring rehospitalization during the first 16 weeks of treatment. The reduction of primary ischemic events did not depend on baseline low-density lipoprotein levels or a subsequent percentage change over the course of this study. These results are likely to be a class effect and not drug specific. Therefore, we recommend that a statin of choice be included in the standard care of patients with ACSs regardless of their initial serum cholesterol levels.

COPYRIGHT 2001 Appleton & Lange
COPYRIGHT 2001 Gale Group