美国马里兰大学医学院Michael Terrin联合内布拉斯加大学医学院B. Timothy Baxter团队探讨了多西环素抑制肾下腹主动脉瘤生长的效果。2020年5月26日，《美国医学会杂志》发布了该成果。

腹主动脉瘤影响超过3％的美国老年人。为了探讨多西环素在两年内是否能抑制腹主动脉瘤的生长，2013年5月至2017年1月，研究组在美国22个临床中心进行了一项平行、两组、随机临床试验，招募了261例肾下小动脉瘤（男性3.5-5.0cm，女性3.5-4.5cm）且年龄超过50岁的患者，将其随机分组，其中133例接受多西环素治疗，128例接受安慰剂治疗，为期2年。主要结果是在基线和2年随访时从CT图像测量的腹主动脉瘤最大横径的变化。

多西环素组中129例患者、安慰剂组125例患者进入初步分析，中位年龄为71.0岁，女性占14%。多西环素组和安慰剂组中动脉瘤修复率分别为10%和7%，死亡率分别为2%和3%。两组间反映主动脉直径变化的正常评分无显著差异。两组基线时肿瘤的最大横向直径分别为4.3厘米。在为期2年的随访中，多西环素组和安慰剂组测量的肿瘤最大横泾变化分别为0.36cm，无显著差异。没有患者因不良反应退出研究。多西环素组中有65%的患者发生关节痛，而安慰剂组中有63%。

总之，对于肾下较小的腹主动脉瘤患者，采用多西环素治疗，与安慰剂相比，并不能显著抑制动脉瘤的生长。

附：英文原文

Title: Effect of Doxycycline on Aneurysm Growth Among Patients With Small Infrarenal Abdominal Aortic Aneurysms: A Randomized Clinical Trial

Author: B. Timothy Baxter, Jon Matsumura, John A. Curci, Ruth McBride, LuAnn Larson, William Blackwelder, Diana Lam, Marniker Wijesinha, Michael Terrin

Issue&Volume: 2020/05/26

Abstract: Importance  Abdominal aortic aneurysms affect more than 3% of US older adults.

Objective  To test whether doxycycline reduces the growth of abdominal aortic aneurysm over 2 years as measured by maximum transverse diameter.

Design, Setting, and Participants  Parallel, 2-group, randomized clinical trial that was conducted at 22 US clinical centers between May 2013 and January 2017, and enrolled patients 50 years or older with small (3.5-5.0 cm for men, 3.5-4.5 cm for women) infrarenal aneurysms. The final date of follow-up was July 31, 2018.

Interventions  Patients were randomized to receive twice daily for 2 years doxycycline 100 mg orally (as capsules) (n=133) or placebo (n=128).

Main Outcomes and Measures  The primary outcome was change in abdominal aortic aneurysm maximum transverse diameter measured from CT images at baseline and follow-up at 2 years. Patients were assigned ranks based on the maximum transverse diameter (measured or imputed) of the aorta and also if they underwent aneurysm repair or died. The ranks were converted to scores having a normal distribution to facilitate the primary analysis (“normal scores”).

Results  Of 261 patients randomized, no follow-up CT scans were obtained on 7 (3%), leaving a final analysis set of 129 patients assigned to doxycycline and 125 to placebo (mean [SD] age, 71.0 years [7.4 years], 35 women [14%]). The outcome normal scores used in the primary analysis were based on maximum transverse diameter (measured or imputed) in 113 patients (88%) in the doxycycline group and 112 patients (90%) in the placebo group; aneurysm repair in 13 (10%) and 9 (7%), and death in 3 (2%) and 4 (3%), respectively. The primary outcome, normal scores reflecting change in aortic diameter, did not differ significantly between the 2 groups, mean change in normal scores, 0.0262 vs 0.0258 (1-sided P=.71). Mean (SD) baseline maximum transverse diameter was 4.3 cm (0.4 cm) for doxycycline and 4.3 cm (0.4 cm) for placebo. At the 2-year follow-up, the change in measured maximum transverse diameter was 0.36 cm (95% CI, 0.31 to 0.40 cm) for 96 patients in the doxycycline group vs 0.36 cm (95% CI, 0.30 to 0.41 cm) for 101 patients in the placebo group (difference, 0.0; 95% CI, 0.07 to 0.07 cm; 2-sided P=.93). No patients were withdrawn from the study because of adverse effects. Joint pain occurred in 84 of 129 patients (65%) with doxycycline and 79 of 125 (63%) with placebo.

Conclusions and Relevance  Among patients with small infrarenal abdominal aortic aneurysms, doxycycline compared with placebo did not significantly reduce aneurysm growth at 2 years. These findings do not support the use of doxycycline for reducing the growth of small abdominal aortic aneurysms.

DOI: 10.1001/jama.2020.5230

Source: https://jamanetwork.com/journals/jama/article-abstract/2766422