title: Randomized secondary prevention trial of azithromycin in patients with coronary artery disease: primary clinical results of the ACADEMIC study.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Division of Cardiology, University of Utah, LDS Hospital, Salt Lake City, Utah 84143, USA. ldbmuhle@ihc.com
authors.forename: J B
authors.initials: JB
authors.lastname: Muhlestein
authors.forename: J L
authors.initials: JL
authors.lastname: Anderson
authors.forename: J F
authors.initials: JF
authors.lastname: Carlquist
authors.forename: K
authors.initials: K
authors.lastname: Salunkhe
authors.forename: B D
authors.initials: BD
authors.lastname: Horne
authors.forename: R R
authors.initials: RR
authors.lastname: Pearson
authors.forename: T J
authors.initials: TJ
authors.lastname: Bunch
authors.forename: A
authors.initials: A
authors.lastname: Allen
authors.forename: S
authors.initials: S
authors.lastname: Trehan
authors.forename: C
authors.initials: C
authors.lastname: Nielson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D017963:Azithromycin / Q000009:adverse effects / Q000627:therapeutic use*; D023521:Chlamydophila Infections / Q000453:epidemiology / Q000382:microbiology / Q000517:prevention & control*; D016993:Chlamydophila pneumoniae; D003327:Coronary Disease / Q000150:complications / Q000382:microbiology / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011446:Prospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin