Azithromycin and coronary events study in patients with stable coronary disease - ACES

Description:

The goal of the ACES trial was to evaluate the use of the antibiotic azithromycin compared with placebo for secondary prevention of coronary events in patients with stable coronary artery disease (CAD).

Hypothesis:

Treatment with the antibiotic azithromycin will be associated with a reduction in coronary events compared with placebo in patients with stable CAD.

Study Design

Study Design:

Patients Enrolled: 4,012
Mean Follow Up: Four years
Mean Patient Age: Mean age 65 years
Female: 20

Patient Populations:

Documented stable CAD

Primary Endpoints:

Composite of CHD death, MI, coronary revascularization, or hospitalization for unstable angina

Drug/Procedures Used:

Patients with stable CAD were randomized to either azithromycin (600 mg once weekly for one year; n=2,004) or placebo (n=2,008). Patients were followed for four years.

Principal Findings:

Baseline characteristics were similar between treatment groups, with 54% of patients in the azithromycin group and 58% in the placebo group having a prior myocardial infarction (MI), and coronary revascularization in 90% and 88%, respectively. Concomitant medications included statins (76%), aspirin (87%), and beta-blockers (60%).

There was no difference in the primary composite endpoint of death due to coronary heart disease (CHD), MI, coronary revascularization, or hospitalization for unstable angina between treatment groups at the end of follow-up (22.3% in the azithromycin group vs. 22.4% in the placebo group, relative risk [RR] 1, p=NS). There was also no difference in any component of the composite endpoint, including CHD death (3.2% vs. 3.7%, RR 13), MI (6.8% vs. 6.5%, RR -5), coronary revascularization (19.0% vs. 18.4%, RR -2), or hospitalization for unstable angina (2.5% vs. 2.7%, RR 9) or the composite of CHD death or MI (9.5% vs. 9.3%, RR -2). There was no difference in titer levels in patients who had an event compared with those who did not have an event.

Interpretation:

Among patients with stable CAD, secondary prevention treatment with the antibiotic azithromycin was not associated with a reduction in coronary events compared with placebo.

The findings of a lack of benefit with antibiotic therapy in the present trial are similar to the findings seen with gatifloxacin in the PROVE IT-TIMI 22 trial and with azithromycin in the WIZARD trial. Given the consistent lack of benefit with use of antibiotics for widespread secondary prevention in acute coronary syndrome, therapy will likely continue to be directed toward other methods of prevention including high-dose statins and ACE inhibitors. Despite the lack of benefit for secondary prevention, the presenter noted that data from these three large trials do not address whether antibiotic therapy may be beneficial for primary prevention of coronary events and development of atherosclerosis, but identification of patients at high risk for such events would be difficult.

References:

Grayston JT, et al. Azithromycin for the Secondary Prevention of Coronary Events. N Engl J Med 2005;352:1637-45.

Grayston JT. ACES: Azithromycin and Coronary Events Study in patients with stable coronary disease. Paper presented at the European Society of Cardiology Congress 2004, 29 August-1 September, Munich, Germany.

Clinical Topics: Acute Coronary Syndromes, Prevention, Novel Agents, Statins

Keywords: Coronary Artery Disease, Myocardial Infarction, Acute Coronary Syndrome, Atherosclerosis, Secondary Prevention, Azithromycin, Fluoroquinolones, Hospitalization


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