(Circulation. 1999;99:1540-1547.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
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
From the Department of Medicine, Division of Cardiology, University of Utah, LDS Hospital, Salt Lake City, Utah.
Correspondence to J. Brent Muhlestein, MD, or Jeffrey L. Anderson, MD, Coprincipal Investigators, Division of Cardiology, LDS Hospital, 8th Ave & C St, Salt Lake City, UT 84143.
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.
Methods and 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]-
), 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.
Key Words: Chlamydia pneumoniae • antibiotics • coronary disease
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