This study included patients admitted with unstable angina or acute myocardial infarction. Short-term treatment with azithromycin did not reduce death or occurrence of ischemic events. In addition, the subgroup of patients without antibodies to Chlamydia pneumoniae did not have a treatment benefit.

The rate of recurrent ischemic events is high in the 6 months following an initial acute coronary syndrome. The cause for recurrent ischemic events is vascular inflammation leading to disruption of plaque and thrombosis. This may be related to infection of the vessel wall with Chlamydia pneumoniae.

Initial studies found azithromycin or roxithromycin treatment reduced inflammation of the vasculature and recurrence of ischemic events. Therefore, treatment with azithromycin, initiated after presentation with acute coronary syndromes, may reduce the occurrence of recurrent ischemic events. This was the hypothesis of the Azithromycin on Recurrent Ischemic Events in Patients with Acute Coronary Syndrome (AZACS) trial.

The AZACS trial was a randomized, double blind, placebo controlled evaluation of patients admitted with acute myocardial infarction or unstable angina. A total of 7 centers participated in the trial.

Investigators randomized 1,439 patients to azithromycin or placebo. The azithromycin dose was 500 mg for 1 day, then 250 mg per day in the following 4 days.

Patients were followed for 6 months. The primary endpoint was all cause mortality, nonfatal myocardial infarction, or recurrent ischemia that required bypass or percutaneous coronary intervention.

Patient characteristics were similar for azithromycin and placebo groups. Mean age was 64 and 65 years, respectively. Approximately one quarter of patients were women.

Results showed no statistically significant difference in primary endpoints between the 2 groups. Incidence of any primary event was 14.3% for placebo and 14.9% for azithromycin. Incidence of individual endpoints (death, nonfatal myocardial infarction, revascularization) was not different.

Investigators prespecified an analysis of data excluding events related to the qualifying event. This was because early events may dilute the potential positive effect of azithromycin later in the trial.

However, this analysis also showed no difference in the composite primary endpoint (12.6% for placebo vs. 12.3% for azithromycin). Again, there were no significant differences in incidence of the specific endpoints of death, nonfatal myocardial infarction and revascularization.

Similarly, there was no difference between azithromycin and placebo for the secondary endpoint of unstable angina/congestive heart failure.

The other prespecified subgroup was the 80% of patients with positive Chlamydia pneumoniae antibody titers. Again, however, investigators found no difference between azithromycin and placebo.

It remains unclear whether there is any role for antibiotic treatment in acute coronary syndromes. However, results of AZACS should be evaluated in context of other studies evaluating different agents and protocols.

Investigators received support from The Heart Fund at Cedars-Sinai and from institutional funds of participating centers.