Treatment of Chlamydia pneumoniae infection with roxithromycin and effect on neointima proliferation after coronary stent placement (ISAR-3): a randomised, double-blind, placebo-controlled trial

Background Vascular infection with Chlamydia pneumoniae might boost inflamm atory responses that play a pivotal part in neointima formation, which is t he main cause of restenosis after stenting. Our aim was to investigate whet her or not treatment of C pneumoniae infection with antibiotics prevents re stenosis after coronary stent placement. Methods We enrolled 1010 consecutive patients with successful coronary sten ting into a randomised, double-blind trial. Patients received the macrolide antibiotic roxithromycin 300 mg once daily for 28 days (506), or placebo ( 504). Primary endpoint was frequency of restenosis (diameter stenosis great er than or equal to 50%) at follow-up angiography, and secondary endpoint w as rate of target vessel revascularisation during the year after stenting. A prespecified secondary analysis addressed treatment effect with respect t o titre of C pneumoniae in serum. Analysis was by intention to treat. Findings Rate of angiographic restenosis was 31% (157 lesions) in the roxit hromycin group and 29% (148) in the placebo group (relative risk 1.08 [95% CI 0.92-1.26]; p=0.43), corresponding to a rate of target vessel revascular isation of 19% (120) and 17% (105), respectively (1.13 [0.95-1.36]; p=0.30) . The combined 1-year rates of death and myocardial infarction were 7% (36) in the roxithromycin group and 6% (30) in the placebo group (p=0.45). We s howed a significant interaction between treatment and C pneumoniae antibody titre (p=0.038 for restenosis, p=0.006 for revascularisation), favouring r oxithromycin at high titres (adjusted odds ratios at a titre of 1/512 were 0.44 [0.19-1.06] and 0.32 [0.13-0.81], respectively). Interpretation Non-selective use of roxithromycin is inadequate for prevent ion of restenosis after coronary stenting. There is, however, a differentia l effect dependent on C pneumoniae titres. In patients with high titres, ro xithromycin reduced the rate of restenosis.