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 inflammatory responses that play a pivotal part in neointima formation, which is the main cause of restenosis after stenting. Our aim was to investigate whether or not treatment of C pneumoniae infection with antibiotics prevents restenosis after coronary stent placement. Methods We enrolled 1010 consecutive patients with successful coronary stenting 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 3=50%) at follow-up angiography, and secondary endpoint was rate of target vessel revascularisation during the year after stenting. A prespecified secondary analysis addressed treatment effect with respect to titre of C pneumoniae in serum. Analysis was by intention to treat. Findings Rate of angiographic restenosis was 31% (157 lesions) in the roxithromycin 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 revascularisation 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 showed a significant interaction between treatment and C pneumoniae antibody titre (p=0·038 for restenosis, p=0·006 for revascularisation), favouring roxithromycin 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 prevention of restenosis after coronary stenting. There is, however, a differential effect dependent on C pneumoniae titres. In patients with high titres, roxithromycin reduced the rate of restenosis.