title: Clarithromycin for 2 weeks for stable coronary heart disease: 6-year follow-up of the CLARICOR randomized trial and updated meta-analysis of antibiotics for coronary heart disease.
abstract: OBJECTIVE
  We have reported increased 2.6-year mortality in clarithromycin- versus placebo-exposed stable coronary heart disease patients, but meta-analysis of randomized trials in coronary heart disease patients showed no significant effect of antibiotics on mortality. Here we report the 6-year mortality of clarithromycin- versus placebo-exposed patients and updated meta-analyses.
  
  
  METHODS
  Centrally randomized, placebo controlled multicenter trial. All parties were blinded. Analyses were by intention to treat. Meta-analyses followed the Cochrane Collaboration methodology.
  
  
  RESULTS
  We randomized 4,372 patients with stable coronary heart disease to clarithromycin 500 mg (n = 2,172) or placebo (n = 2,200) once daily for 2 weeks. Mortality was followed through public register. Nine hundred and twenty-three patients (21.1%) died. Six-year mortality was significantly higher in the clarithromycin group (hazard ratio 1.21, 95% confidence interval 1.06-1.38). Adjustment for entry characteristics (sex, age, prior myocardial infarction, center, and smoking) did not change the results (1.18, 1.04-1.35). Addition of our data to that of other randomized trials on antibiotics for patients with coronary heart disease versus placebo/no intervention (17 trials, 25,271 patients, 1,877 deaths) showed a significantly increased relative risk of death from antibiotics of 1.10 (1.01-1.20) without heterogeneity.
  
  
  CONCLUSIONS
  Our results stress the necessity to consider carefully the strength of the indication before administering antibiotics to patients with coronary heart disease.
authors.affiliation: The Copenhagen Trial Unit, Center for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. cgluud@ctu.rh.dk
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
authors.forename: Bodil
authors.initials: B
authors.lastname: Als-Nielsen
authors.forename: Morten
authors.initials: M
authors.lastname: Damgaard
authors.forename: Jørgen
authors.initials: J
authors.lastname: Fischer Hansen
authors.forename: Stig
authors.initials: S
authors.lastname: Hansen
authors.forename: Olav H
authors.initials: OH
authors.lastname: Helø
authors.forename: Per
authors.initials: P
authors.lastname: Hildebrandt
authors.forename: Jørgen
authors.initials: J
authors.lastname: Hilden
authors.forename: Gorm Boje
authors.initials: GB
authors.lastname: Jensen
authors.forename: Jens
authors.initials: J
authors.lastname: Kastrup
authors.forename: Hans Jørn
authors.initials: HJ
authors.lastname: Kolmos
authors.forename: Erik
authors.initials: E
authors.lastname: Kjøller
authors.forename: Inga
authors.initials: I
authors.lastname: Lind
authors.forename: Henrik
authors.initials: H
authors.lastname: Nielsen
authors.forename: Lars
authors.initials: L
authors.lastname: Petersen
authors.forename: Christian M
authors.initials: CM
authors.lastname: Jespersen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D017291:Clarithromycin / Q000008:administration & dosage* / Q000009:adverse effects*; D016001:Confidence Intervals; D003327:Coronary Disease / Q000188:drug therapy* / Q000401:mortality*; D003718:Denmark; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D016017:Odds Ratio; D012306:Risk; D016019:Survival Analysis
chemical_list: D000900:Anti-Bacterial Agents; D017291:Clarithromycin