通过根除肺炎衣原体进行动脉粥样硬化二级预防（SPACE试验）：一项针对外周动脉疾病患者的随机临床试验。

Secondary prevention of atherosclerosis through chlamydia pneumoniae eradication (SPACE Trial): a randomised clinical trial in patients with peripheral arterial disease.

作者信息

Vainas T, Stassen F R M, Schurink G W H, Tordoir J H M, Welten R J Th J, van den Akker L H J M, Kurvers H A J M, Bruggeman C A, Kitslaar P J E H M

机构信息

Department of Surgery, Maastricht University Hospital, PO Box 5800, 6202 AZ Maastricht, The Netherlands.

出版信息

Eur J Vasc Endovasc Surg. 2005 Apr;29(4):403-11. doi: 10.1016/j.ejvs.2005.01.001.

DOI:10.1016/j.ejvs.2005.01.001

PMID:15749042

Abstract

BACKGROUND

Sero-epidemiological and experimental studies suggest that Chlamydia pneumoniae infections play an important role in the development of atherosclerosis. Clinical trials have shown contradictory results regarding the efficacy of antibiotics to prevent atherosclerosis-related complications in patients with coronary artery disease. Our aim was to study the effect of a short course of azithromycin on the incidence of cardiovascular events and peripheral vascular function in patients with stable peripheral arterial disease (PAD).

PATIENTS AND METHODS

Five hundred and nine PAD-patients were randomised to receive either a 3-day course of azithromycin (500 mg daily) or placebo, with 2 years of follow-up. C. pneumoniae serology was determined at baseline. Clinical endpoints were death, coronary events (myocardial infarction, unstable angina, and/or coronary revascularization procedures), cerebral events (stroke, TIA, and/or carotid endarterectomy) and peripheral arterial complications (increased PAD-symptoms with decreased ankle-brachial index (ABPI, 0.1-point decrease after 12 months), and/or peripheral revascularization procedures).

RESULTS

Five hundred and nine patients (160 women) with an atherosclerotic risk factor profile were randomised, 257 patients to azithromycin and 252 to placebo. Four hundred and forty nine patients (88%) had intermittent claudication and 60 (12%) had critical limb ischemia. By 24-month follow up, 182 patients (36%) developed 252 complications (45 deaths, 34 coronary events, 34 cerebral events and 139 peripheral arterial complications). C. pneumoniae IgA-titres were associated with the development of cardiovascular events. Nevertheless, the number of complications (131 in the azithromycin group vs. 121 in the placebo group) and the number of patients that developed complications (98 (38%) in the azithromycin vs. 84 (33%) in the placebo group) was comparable in both treatment groups. Life table analysis showed no effect of azithromycin on survival or ABPI.

CONCLUSION

A short-term course of azithromycin offers no benefits for survival or ankle pressure in PAD-patients.

摘要

背景

血清流行病学和实验研究表明，肺炎衣原体感染在动脉粥样硬化的发展中起重要作用。关于抗生素预防冠心病患者动脉粥样硬化相关并发症的疗效，临床试验结果相互矛盾。我们的目的是研究短期服用阿奇霉素对稳定型外周动脉疾病（PAD）患者心血管事件发生率和外周血管功能的影响。

患者与方法

509例PAD患者被随机分为两组，一组接受为期3天的阿奇霉素治疗（每日500毫克），另一组接受安慰剂治疗，随访2年。在基线时测定肺炎衣原体血清学。临床终点包括死亡、冠状动脉事件（心肌梗死、不稳定型心绞痛和/或冠状动脉血运重建术）、脑部事件（中风、短暂性脑缺血发作和/或颈动脉内膜切除术）以及外周动脉并发症（PAD症状加重伴踝臂指数（ABPI）降低（12个月后降低0.1个百分点）和/或外周血运重建术）。

结果

509例有动脉粥样硬化危险因素的患者（160例女性）被随机分组，257例患者接受阿奇霉素治疗，252例接受安慰剂治疗。449例患者（88%）有间歇性跛行，60例（12%）有严重肢体缺血。到24个月随访时，182例患者（36%）出现了252种并发症（45例死亡、34例冠状动脉事件、34例脑部事件和139例外周动脉并发症）。肺炎衣原体IgA滴度与心血管事件的发生有关。然而，两组治疗中并发症的数量（阿奇霉素组131例，安慰剂组121例）以及出现并发症的患者数量（阿奇霉素组98例（38%），安慰剂组84例（33%））相当。生命表分析显示阿奇霉素对生存率或ABPI没有影响。