Azithromycin for the secondary prevention of coronary heart disease events - The WIZARD study: A randomized controlled trial
Azithromycin for the secondary prevention of coronary heart disease events - The WIZARD study: A randomized controlled trial
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DOI：
10.1001/jama.290.11.1459
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发表时间：
2003-09-17
影响因子：
120.7
通讯作者：
Cook, TD
中科院分区：
文献类型：
--
作者：
O'Connor, CM;Dunne, MW;Cook, TD
一些证据表明肺炎衣原体感染与动脉粥样硬化发生之间存在关联。目的探讨稳定型冠状动脉疾病及已知肺炎原体暴露患者12周抗生素治疗对冠心病事件的影响。设计、环境和参与者：随机、安慰剂对照试验，7747例既往心肌梗死至少发生6周（中位，2.6年）且肺炎C IgG滴度为1:16或更高的成年人。从1997年10月10日至2001年7月22日，患者从北美、欧洲、阿根廷和印度的271个临床诊所招募。干预措施患者在第1周接受阿奇霉素（600 mg/d，连续3天，然后在第2-12周接受600 mg/周；n = 3879）或安慰剂（n = 3868）。主要结局指标主要事件为首次发生任何原因死亡、非致死性再梗死、冠状动脉血运重建术或因心绞痛住院。对患者进行随访，直到发生1038起事件。结果中位随访14个月后，与安慰剂相比，阿奇霉素组发生原发性事件的可能性没有显著降低（7%[95%置信区间，-5%至17%]，P= 0.23）。风险比分析表明，早期阿奇霉素对原发事件和死亡或再梗死的益处，但随着时间的推移，这些益处逐渐减少。主要终点的任何组成部分，包括死亡（8%）、复发性心肌梗死（7%）、血运重建术（5%）或因心绞痛住院（-1%），都没有显著的风险降低。在随机接受阿奇霉素治疗的患者中，有13.2%的患者报告了与研究药物相关的不良事件，主要是腹泻，而随机接受安慰剂治疗的患者中有4.6%的患者报告了与研究药物相关的不良事件，服用阿奇霉素的患者中有1.6%的患者报告了停药，服用安慰剂的患者中有0.4%的患者报告了停药。结论在既往心肌梗死且有肺炎C暴露证据的稳定患者中，3个月疗程的阿奇霉素并没有显著减少冠心病的临床后遗症。
Context Several lines of evidence have implied an association between Chlamydia pneumoniae infection and atherogenesis.Objective To determine the effect of 12 weeks of antibiotic therapy on coronary heart disease events in patients with stable coronary artery disease and known C pneumoniae exposure.Design, Setting, and Participants Randomized, placebo-controlled trial of 7747 adults with previous myocardial infarction that had occurred at least 6 weeks previously (median, 2.6 years) and a C pneumoniae IgG titer of 1:16 or more. Patients were recruited from 271 clinical practices in North America, Europe, Argentina, and India, from October 10, 1997, to July 22, 2001.Intervention The patients received either azithromycin (600 mg/d for 3 days during week 1, then 600 mg/wk during weeks 2-12; n = 3879) or placebo (n = 3868).Main Outcome Measures The primary event was the first occurrence of death from any cause, nonfatal reinfarction, coronary revascularization, or hospitalization for angina. Patients were followed up until 1038 events accrued.Results After a median of 14 months of follow-up, there was no significant risk reduction in the likelihood of a primary event with azithromycin vs placebo (7% [95% confidence interval, -5% to 17%], P=.23). Analysis of hazard ratios suggested early benefits of azithromycin on the primary event and on death or reinfarction, but these decreased over time. There were no significant risk reductions for any of the components of the primary end point including death (8%), recurrent myocardial infarction (7%), revascularization procedures (5%), or hospitalizations for angina (-1%). Adverse events related to study drug were reported by 13.2% of those randomized to receive azithromycin, predominantly a result of diarrhea, compared with 4.6% randomized to receive placebo, and resulted in discontinuation of drug in 1.6% of those taking azithromycin and 0.4% taking placebo.Conclusion Among stable patients with previous myocardial infarction and with evidence of C pneumoniae exposure, a 3-month course of azithromycin did not significantly reduce the clinical sequelae of coronary heart disease.