Gluud Christian, Als-Nielsen Bodil, Damgaard Morten, Fischer Hansen Jørgen, Hansen Stig, Helø Olav H, Hildebrandt Per, Hilden Jørgen, Jensen Gorm Boje, Kastrup Jens, Kolmos Hans Jørn, Kjøller Erik, Lind Inga, Nielsen Henrik, Petersen Lars, Jespersen Christian M
The Copenhagen Trial Unit, Center for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Cardiology. 2008;111(4):280-7. doi: 10.1159/000128994. Epub 2008 May 2.
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.
Centrally randomized, placebo controlled multicenter trial. All parties were blinded. Analyses were by intention to treat. Meta-analyses followed the Cochrane Collaboration methodology.
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.
Our results stress the necessity to consider carefully the strength of the indication before administering antibiotics to patients with coronary heart disease.
我们曾报道，与服用安慰剂的稳定型冠心病患者相比，服用克拉霉素的患者2.6年死亡率有所增加，但对冠心病患者随机试验的荟萃分析表明，抗生素对死亡率无显著影响。在此，我们报告服用克拉霉素与服用安慰剂患者的6年死亡率，并更新荟萃分析。
进行中心随机、安慰剂对照的多中心试验。所有参与方均为盲法。分析采用意向性治疗。荟萃分析遵循Cochrane协作组方法。
我们将4372例稳定型冠心病患者随机分为两组，一组每日服用一次500毫克克拉霉素（n = 2172），另一组服用安慰剂（n = 2200），为期2周。通过公共登记系统跟踪死亡率。923例患者（21.1%）死亡。克拉霉素组的6年死亡率显著更高（风险比1.21，95%置信区间1.06 - 1.38）。对入组特征（性别、年龄、既往心肌梗死、中心和吸烟情况）进行调整后，结果未改变（1.18，1.04 - 1.35）。将我们的数据与其他关于冠心病患者使用抗生素与安慰剂/无干预的随机试验数据（17项试验，25271例患者，1877例死亡）合并分析显示，抗生素导致的死亡相对风险显著增加至1.10（1.01 - 1.20），且无异质性。
我们的结果强调，在对冠心病患者使用抗生素之前，必须仔细考虑用药指征的强度。
