Christian Gluud a, b , Bodil Als-Nielsen c , Morten Damgaard d , Jørgen Fischer Hansen d , Stig Hansen e , Olav H. Helø f , Per Hildebrandt g , Jørgen Hilden h , Gorm Boje Jensen e , Jens Kastrup f , Hans Jørn Kolmos i , Erik Kjøller j , Inga Lind k , Henrik Nielsen c , Lars Petersen g , Christian M. Jespersen a, d
02 May 2008
Objectives: 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.