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.
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.
Gluud
Christian
C
The Copenhagen Trial Unit, Center for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. cgluud@ctu.rh.dk
Als-Nielsen
Bodil
B
Damgaard
Morten
M
Fischer Hansen
Jørgen
J
Hansen
Stig
S
Helø
Olav H
OH
Hildebrandt
Per
P
Hilden
Jørgen
J
Jensen
Gorm Boje
GB
Kastrup
Jens
J
Kolmos
Hans Jørn
HJ
Kjøller
Erik
E
Lind
Inga
I
Nielsen
Henrik
H
Petersen
Lars
L
Jespersen
Christian M
CM
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
D000900:Anti-Bacterial Agents; D017291:Clarithromycin