Analysis Group, Inc., Boston, Massachusetts, USA.
Veterans Affairs Medical Center, White River Junction, Vermont, USA.
Pharmacoepidemiol Drug Saf. 2022 Aug;31(8):840-850. doi: 10.1002/pds.5451. Epub 2022 May 24.
Azithromycin is a common first-line antibiotic for respiratory infection; however, there is conflicting evidence regarding risk of cardiovascular death. We assessed cardiovascular and noncardiovascular mortality associated with azithromycin versus amoxicillin-clavulanate among US Veterans treated for nonear-nose-throat respiratory infection ("respiratory") or ear-nose-throat infection indication.
Electronic health record data from the US Veterans Health Administration database were used to identify Veterans (30-74 years) with outpatient dispensings of oral azithromycin versus amoxicillin-clavulanate for respiratory or ear-nose-throat infection (January 01, 2000-December 31, 2014). Outcomes assessed were risk of cardiovascular death and noncardiovascular death within 1-5 and 6-10 days postdispensing. Inverse probability of treatment-weighted proportional hazards models and binomial regression models were used to estimate hazard ratios (HRs) and compute risk differences (RD) per million courses of therapy. Cardiac death (subset of cardiovascular death) was assessed in sensitivity analyses.
There were 629 345 azithromycin and 168 429 amoxicillin-clavulanate dispensings for respiratory indications, 143 783 azithromycin, and 203 142 amoxicillin-clavulanate dispensings for ear-nose-throat indications. For respiratory indications, azithromycin was not associated with a significantly different risk of cardiovascular death versus amoxicillin-clavulanate within 1-5 days postdispensing (HR [95% confidence interval (CI)]: 1.12 [0.63, 2.00]; RD [95% CI]: 11 [-43, 64] deaths/million courses of therapy). No elevated risk for azithromycin was found for ear-nose-throat indications. Pooled results for both indications via meta-analysis showed no association between antibiotics and cardiovascular mortality. There was no significant difference in risk of noncardiovascular or cardiac death between antibiotics postdispensing.
Azithromycin was not associated with elevated risk of cardiovascular or noncardiovascular death versus amoxicillin-clavulanate among US Veterans.
阿奇霉素是治疗呼吸道感染的常用一线抗生素；然而，关于其导致心血管死亡的风险，证据相互矛盾。我们评估了美国退伍军人因非耳鼻喉（“呼吸道”）或耳鼻喉感染而接受阿奇霉素与阿莫西林-克拉维酸治疗后的心血管和非心血管死亡率与阿奇霉素与阿莫西林-克拉维酸的关系。
使用美国退伍军人健康管理局数据库中的电子健康记录数据，确定 2000 年 1 月 1 日至 2014 年 12 月 31 日期间因呼吸道或耳鼻喉感染而接受门诊阿奇霉素与阿莫西林-克拉维酸治疗的退伍军人（30-74 岁）。评估的结果是在配药后 1-5 天和 6-10 天内的心血管死亡和非心血管死亡风险。使用逆概率治疗加权比例风险模型和二项式回归模型估计风险比（HR）并计算每百万疗程的风险差异（RD）。在敏感性分析中评估了心脏死亡（心血管死亡的一个子集）。
在呼吸道指征方面，有 629345 例阿奇霉素和 168429 例阿莫西林-克拉维酸处方，在耳鼻喉指征方面，有 143783 例阿奇霉素和 203142 例阿莫西林-克拉维酸处方。对于呼吸道指征，与阿莫西林-克拉维酸相比，阿奇霉素在配药后 1-5 天内的心血管死亡风险无显著差异（HR [95%置信区间（CI）]：1.12 [0.63, 2.00]；RD [95%CI]：11 [-43, 64] 例/百万疗程）。对于耳鼻喉指征，阿奇霉素没有发现风险增加。通过荟萃分析对两种指征的汇总结果表明，抗生素与心血管死亡率之间没有关联。配药后抗生素与非心血管或心脏死亡的风险没有显著差异。
在美国退伍军人中，与阿莫西林-克拉维酸相比，阿奇霉素与心血管或非心血管死亡的风险增加无关。
