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

Lancet. 2001 Jun 30;357(9274):2085-9. doi: 10.1016/s0140-6736(00)05181-3.


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 >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]; p50.43), corresponding to a rate of target vessel revascularisation of 19% (120) and 17% (105), respectively (1.13 [0.95-1.36]; p50.30). The combined 1-year rates of death and myocardial infarction were 7% (36) in the roxithromycin group and 6% (30) in the placebo group (p50.45). We showed a significant interaction between treatment and C pneumoniae antibody titre (p50.038 for restenosis, p50.006 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Antibodies, Bacterial / blood
  • Cell Division / drug effects
  • Chlamydophila Infections / complications*
  • Chlamydophila Infections / drug therapy*
  • Chlamydophila pneumoniae* / immunology
  • Coronary Angiography
  • Coronary Disease / complications*
  • Coronary Disease / diagnostic imaging
  • Coronary Disease / pathology
  • Coronary Disease / therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Prospective Studies
  • Recurrence
  • Roxithromycin / pharmacology
  • Roxithromycin / therapeutic use*
  • Stents*
  • Survival Analysis
  • Tunica Intima / drug effects
  • Tunica Intima / pathology*


  • Anti-Bacterial Agents
  • Antibodies, Bacterial
  • Roxithromycin