Randomized Secondary Prevention Trial of Azithromycin in Patients With Coronary Artery Disease and Serological Evidence for Chlamydia pneumoniae Infection

Abstract

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]-α), 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.