Patients experience the highest rate of death and recurrent ischemic
events during the early period after an acute coronary syndrome, but it is
not known whether early initiation of treatment with a statin can reduce the
occurrence of these early events.
To determine whether treatment with atorvastatin, 80 mg/d, initiated
24 to 96 hours after an acute coronary syndrome, reduces death and nonfatal
Design and Setting
A randomized, double-blind trial conducted from May 1997 to September
1999, with follow-up through 16 weeks at 122 clinical centers in Europe, North
America, South Africa, and Australasia.
A total of 3086 adults aged 18 years or older with unstable angina or
non–Q-wave acute myocardial infarction.
Patients were stratified by center and randomly assigned to receive
treatment with atorvastatin (80 mg/d) or matching placebo between 24 and 96
hours after hospital admission.
Main Outcome Measures
Primary end point event defined as death, nonfatal acute myocardial
infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial
ischemia with objective evidence and requiring emergency rehospitalization.
A primary end point event occurred in 228 patients (14.8%) in the atorvastatin
group and 269 patients (17.4%) in the placebo group (relative risk [RR], 0.84;
95% confidence interval [CI], 0.70-1.00; P = .048).
There were no significant differences in risk of death, nonfatal myocardial
infarction, or cardiac arrest between the atorvastatin group and the placebo
group, although the atorvastatin group had a lower risk of symptomatic ischemia
with objective evidence and requiring emergency rehospitalization (6.2% vs
8.4%; RR, 0.74; 95% CI, 0.57-0.95; P = .02). Likewise,
there were no significant differences between the atorvastatin group and the
placebo group in the incidence of secondary outcomes of coronary revascularization
procedures, worsening heart failure, or worsening angina, although there were
fewer strokes in the atorvastatin group than in the placebo group (12 vs 24
events; P = .045). In the atorvastatin group, mean
low-density lipoprotein cholesterol level declined from 124 mg/dL (3.2 mmol/L)
to 72 mg/dL (1.9 mmol/L). Abnormal liver transaminases (>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).
For patients with acute coronary syndrome, lipid-lowering therapy with
atorvastatin, 80 mg/d, reduces recurrent ischemic events in the first 16 weeks,
mostly recurrent symptomatic ischemia requiring rehospitalization.