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.
BACKGROUND
Chlamydia pneumoniae commonly causes respiratory infection, is vasotropic, causes atherosclerosis in animal models, and has been found in human atheromas. Whether it plays a causal role in clinical coronary artery disease (CAD) and is amenable to antibiotic therapy is uncertain.


RESULTS
CAD patients (n=302) who had a seropositive reaction to C pneumoniae (IgG titers >/=1:16) were randomized to receive placebo or azithromycin, 500 mg/d for 3 days, then 500 mg/wk for 3 months. Circulating markers of inflammation (C-reactive protein [CRP], interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-alpha), C pneumoniae antibody titers, and cardiovascular events were assessed at 3 and 6 months. Treatment groups were balanced, with age averaging 64 (SD=10) years; 89% of the patients were male. Azithromycin reduced a global rank sum score of the 4 inflammatory markers at 6 (but not 3) months (P=0. 011) as well as the mean global rank sum change score: 531 (SD=201) for active drug and 587 (SD=190) for placebo (P=0.027). Specifically, change-score ranks were significantly lower for CRP (P=0.011) and IL-6 (P=0.043). Antibody titers were unchanged, and number of clinical cardiovascular events at 6 months did not differ by therapy (9 for active drug, 7 for placebo). Azithromycin decreased infections requiring antibiotics (1 versus 12 at 3 months, P=0.002) but caused more mild, primarily gastrointestinal, adverse effects (36 versus 17, P=0.003).


CONCLUSIONS
In CAD patients positive for C pneumoniae antibodies, global tests of 4 markers of inflammation improved at 6 months with azithromycin. However, unlike another smaller study, no differences in antibody titers and clinical events were observed. Longer-term and larger studies of antichlamydial therapy are indicated.
Anderson
J L
JL
Department of Medicine, Division of Cardiology, University of Utah, LDS Hospital, Salt Lake City, Utah 84143, USA.
Muhlestein
J B
JB
Carlquist
J
J
Allen
A
A
Trehan
S
S
Nielson
C
C
Hall
S
S
Brady
J
J
Egger
M
M
Horne
B
B
Lim
T
T
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000907:Antibodies, Bacterial / Q000097:blood; D017963:Azithromycin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D002690:Chlamydia Infections / Q000188:drug therapy*; D016993:Chlamydophila pneumoniae / Q000276:immunology; D003327:Coronary Disease / Q000188:drug therapy* / Q000517:prevention & control; D004311:Double-Blind Method; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010342:Patient Acceptance of Health Care; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D017963:Azithromycin; D002097:C-Reactive Protein