Azithromycin in Acute Coronary Syndrome - AZACS


The goal of Azithromycin in Acute Coronary Syndrome (AZACS) was to evaluate whether short-term treatment with azithromycin, a microlide antibiotic, can prevent death or further cardiac problems after unstable angina or acute myocardial infarction (MI) in patients with prior infection by chlamydia pneumoniae.


The rationale behind AZACS was that vascular inflammation leading to plaque disruption and acute coronary syndrome (ACS) may be, in part, due to infection.

Study Design

Study Design:

Patients Screened: 7,100
Patients Enrolled: 1,439
Mean Follow Up: Six months
Mean Patient Age: Mean age of 65 years
Female: 28%

Patient Populations:

Age ≥18 years and admitted with unstable angina or acute MI.


Q-wave MI within the past 28 days of the current admission; pregnant or breastfeeding; deemed unreliable as study participant; participating in another clinical study; had known hypersensitivity to azithromycin, erythromycin, or any macrolide antibiotic; or had other important diseases or comorbidities (e.g., terminal cancer, life-threatening infection) that could compromise the patient’s safety or participation in the study.

Primary Endpoints:

Composite of death, nonfatal MI, and recurrent ischemia necessitating revascularization.

Secondary Endpoints:

Worsening of ischemic symptoms or congestive heart failure requiring admission.

Drug/Procedures Used:

The randomized, double-blind, placebo-controlled trial tested a strategy of short-term azithromycin therapy on the occurrence of clinical events in patients with ACS. A total of 1,439 patients with ACS were randomized to azithromycin (n=716), 500 mg for one day followed by 250 mg/day for four days, or matching placebo (n=723). The primary end point was a composite of death, nonfatal MI, and recurrent ischemia necessitating revascularization at six months.

Principal Findings:

Mean time from qualifying diagnosis to randomization was 2.9 days. The primary composite end point occurred in 14.3% of placebo recipients and 14.9% of azithromycin-treated patients (hazard ratio [HR] 0.94, p=0.664). There was no difference in any of the individual components of the composite end point by treatment group. There was also no difference in patients presenting with acute MI (n=826) (14% vs. 14%, HR 1.03, p=0.860) or those with serological evidence of prior C pneumonia infection (n=939; 15% azithromycin vs. 14% placebo, HR 1.06, p=0.230). There was also no difference in the secondary end point of ischemia or congestive heart failure (CHF) requiring admission, which occurred in 9% of patients in the azithromycin arm and 8% in the placebo arm (HR 1.07, p=0.707).


Among patients with acute MI or unstable angina, short-term treatment with azithromycin was not associated with a reduction in the recurrence of ischemic events or death during follow-up for six months. The results of this trial, while negative, are not generalizable to other antibiotics or other anti-inflammatory agents. Whether differing agents, duration of therapy, and follow-up in other patients with atherosclerotic vascular disease will reveal beneficial effects remains to be determined in upcoming larger randomized trials such as PROVE-IT and ACES. Trials to date have shown conflicting results. The WIZARD trial showed a nonsignificant reduction of the primary end point in patients treated with long-term azithromycin therapy, while the STAMINA trial showed a significant reduction in the primary end point of event-free survival in patients treated with short-term use of amoxicillin or azithromycin.


Cercek B, Shah PK, Noc M, et al. Effect of short-term treatment with azithromycin on recurrent ischaemic events in patients with acute coronary syndrome in the Azithromycin in Acute Coronary Syndrome (AZACS) trial: a randomised controlled trial. Lancet. 2003;361:809-13.

Keywords: Inflammation, Myocardial Infarction, Acute Coronary Syndrome, Pneumonia, Follow-Up Studies, Heart Failure, Azithromycin, Disease-Free Survival, Chlamydophila pneumoniae

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