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 >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.


RESULTS
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).


CONCLUSIONS
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.
Neumann
F
F
Medizinische Klinik, Technische Universität München, 81675, München, Germany. neumann@dhm.mhn.de
Kastrati
A
A
Miethke
T
T
Pogatsa-Murray
G
G
Mehilli
J
J
Valina
C
C
Jogethaei
N
N
da Costa
C P
CP
Wagner
H
H
Schömig
A
A
D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000907:Antibodies, Bacterial / Q000097:blood; D002455:Cell Division / Q000187:drug effects; D023521:Chlamydophila Infections / Q000150:complications* / Q000188:drug therapy*; D016993:Chlamydophila pneumoniae / Q000276:immunology; D017023:Coronary Angiography; D003327:Coronary Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D015575:Roxithromycin / Q000494:pharmacology / Q000627:therapeutic use*; D015607:Stents; D016019:Survival Analysis; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*
D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D015575:Roxithromycin