Randomized secondary prevention trial of azithromycin in patients with coronary artery disease : Primary clinical results of the ACADEMIC study

• Published in: Circulation (New York, N.Y.) N.Y.), 2000-10, Vol.102 (15), p.1755-1760
• Main Authors: MUHLESTEIN, Joseph B, ANDERSON, Jeffrey L, CARLQUIST, John F, SALUNKHE, Kirti, HORNE, Benjamin D, PEARSON, Robert R, BUNCH, T. Jared, ALLEN, Ann, TREHAN, Sanjeev, NIELSON, Cindy
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Antibacterial agents; Antibiotic Prophylaxis; Antibiotics. Antiinfectious agents. Antiparasitic agents; Azithromycin - adverse effects; Azithromycin - therapeutic use; Biological and medical sciences; Chlamydophila Infections - epidemiology; Chlamydophila Infections - microbiology; Chlamydophila Infections - prevention & control; Chlamydophila pneumoniae; Coronary Disease - complications; Coronary Disease - microbiology; Coronary Disease - prevention & control; Double-Blind Method; Female; Humans; Male; Medical sciences; Middle Aged; Patient Compliance; Pharmacology. Drug treatments; Prospective Studies
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.102.15.1755

Chlamydia pneumoniae is associated with coronary artery disease (CAD), although its causal role is uncertain. A small preliminary study reported a >50% reduction in ischemic events by azithromycin, an antibiotic effective against C pneumoniae, in seropositive CAD patients. We tested this prospectively in a larger, randomized, double-blind study. CAD patients (n=302) seropositive to C pneumoniae (IgG titers >/=1:16) were randomized to placebo or azithromycin 500 mg/d for 3 days and then 500 mg/wk for 3 months. The primary clinical end point included cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction (MI), stroke, unstable angina, and unplanned coronary revascularization at 2 years. Treatment groups were balanced, and azithromycin was generally well tolerated. During the trial, 47 first primary events occurred (cardiovascular death, 9; resuscitated cardiac arrest, 1; MI, 11; stroke, 3; unstable angina, 4; and unplanned coronary revascularization, 19), with 22 events in the azithromycin group and 25 in the placebo group. There was no significant difference in the 1 primary end point between the 2 groups (hazard ratio for azithromycin, 0.89; 95% CI, 0.51 to 1.61; P:=0.74). Events included 9 versus 7 occurring within 6 months and 13 versus 18 between 6 and 24 months in the azithromycin and placebo groups, respectively. This study suggests that antibiotic therapy with azithromycin is not associated with marked early reductions (>/=50%) in ischemic events as suggested by an initial published report. However, a clinically worthwhile benefit (ie, 20% to 30%) is still possible, although it may be delayed. Larger (several thousand patient), longer-term (>/=3 to 5 years) antibiotic studies are therefore indicated.