Randomized secondary prevention trial of azithromycin in patients with coronary artery disease: primary clinical results of the ACADEMIC study.
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.
Muhlestein
J B
JB
Department of Medicine, Division of Cardiology, University of Utah, LDS Hospital, Salt Lake City, Utah 84143, USA. ldbmuhle@ihc.com
Anderson
J L
JL
Carlquist
J F
JF
Salunkhe
K
K
Horne
B D
BD
Pearson
R R
RR
Bunch
T J
TJ
Allen
A
A
Trehan
S
S
Nielson
C
C
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
D000900:Anti-Bacterial Agents; D017963:Azithromycin