Azithromycin in Coronary Artery Disease: Elimination of Myocardial Infection With Chlamydia - ACADEMIC

Description:

The Azithromycin in Coronary Artery Disease: Elimination of Myocardial Infection With Chlamydia (ACADEMIC) study was a randomized controlled trial of azithromycin versus placebo for the secondary prevention of coronary artery disease (CAD).

Hypothesis:

Administration of azithromycin to patients with known CAD and positive Chlamydia pneumoniae serologies would reduce global markers of inflammation and cardiovascular events.

Study Design

Study Design:

Patients Screened: 430
Patients Enrolled: 302
Mean Follow Up: 2 years
Mean Patient Age: average age 64
Female: 14

Patient Populations:

CAD (prior MI, coronary artery bypass graft [CABG], >50% angiographic stenosis), and age >18

Exclusions:

New York Heart Association class III/IV heart failure, left ventricular ejection fraction <25%, MI within five days, recent CABG or percutaneous coronary intervention, significant comorbid illnesses (malignancy, hemodialysis, liver failure, drug/alcohol abuse), female of child-bearing age without birth control, intolerance to azithromycin, or chronic macrolide/tetracycline use

Primary Endpoints:

1) Laboratory: Global (aggregate) measure of systemic levels of CRP, IL-1, IL-6, and TNF-α; and 2) Clinical: Combined endpoint of cardiovascular death, resuscitated cardiovascular arrest, nonfatal myocardial infarction (MI) or stroke, unstable angina requiring hospitalization, and unplanned coronary interventions

Secondary Endpoints:

1) Laboratory: antichlamydial antibody levels; and 2) Clinical: all deaths, other cardiovascular hospitalizations/procedures, adverse experiences/discontinuations, and clinical infections

Drug/Procedures Used:

Azithromycin 500 mg/day for three days, and then 500 mg/wk for three months versus placebo

Concomitant Medications:

No restrictions aside from pre-existing macrolide/tetracycline use

Principal Findings:

In 302 patients with known CAD and positive Chlamydia pneumoniae titers, azithromycin, compared to placebo, resulted in a reduction of a global score of four inflammatory markers (C-reactive protein [CRP], interleukin [IL]-1, IL-6, tumor necrosis factor [TNF]-α) with average rank sum scores of 532 for azithromycin versus 598 for placebo (p=0.011). There was also a difference in change in global scores from baseline at six months (average rank sum score for change in values compared to baseline of 531 for azithromycin vs. 587 for placebo, p=0.027).

There was no significant change in Chlamydia titers. There were no significant differences in clinical cardiovascular endpoints at up to two years between groups (22 events in the azithromycin group vs. 25 events in the placebo group, hazard ratio [HR] 0.89, p=0.74).

Interpretation:

Among patients with CAD and positive Chlamydia pneumoniae titers, azithromycin therapy resulted in decreases in several markers of inflammation at six months. However, there was a lack of a significant clinical benefit at any of the timepoints in up to two years of follow-up.

It is possible that the relatively small sample size of this study limited its power to detect a clinical difference in therapy, and larger trials are underway to further test this hypothesis.

References:

1. Anderson JL, Muhlestein JB, Carlquist J, et al. Randomized secondary prevention trial of azithromycin in patients with coronary artery disease and serological evidence for Chlamydia pneumoniae infection: The Azithromycin in Coronary Artery Disease: Elimination of Myocardial Infection with Chlamydia (Academic) Study. Circulation 1999;99:1540-7.

2. Muhlestein JB, Anderson JL, Carlquist JF, et al. Randomized secondary prevention trial of azithromycin in patients with coronary artery disease: primary clinical results of the ACADEMIC study. Circulation 2000;102:1755-60.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Prevention, Cardiac Surgery and Arrhythmias, Interventions and Coronary Artery Disease

Keywords: Inflammation, Coronary Artery Disease, C-Reactive Protein, Secondary Prevention, Interleukin-6, Azithromycin, Chlamydophila pneumoniae, Constriction, Pathologic, Tumor Necrosis Factor-alpha, Chlamydia Infections, Coronary Artery Bypass, Interleukin-1


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