Division of Research, Kaiser Permanente Northern California, Oakland.
School of Pharmacy, Chapman University, Irvine, California.
JAMA Netw Open. 2020 Jun 1;3(6):e208199. doi: 10.1001/jamanetworkopen.2020.8199.
Azithromycin is one of the most commonly prescribed antibiotics in the US. It has been associated with an increased risk of cardiovascular death in some observational studies.
To estimate the relative and absolute risks of cardiovascular and sudden cardiac death after an outpatient azithromycin prescription compared with amoxicillin, an antibiotic not known to increase cardiovascular events.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 2 large, diverse, community-based integrated care delivery systems with comprehensive capture of encounters and prescriptions from January 1, 1998, to December 31, 2014. The cohort included patients aged 30 to 74 years who had at least 12 months of health-plan enrollment prior to antibiotic exposure. The exclusion criteria were absence of prescription benefits, prescription for more than 1 type of study antibiotic within 10 days, hospitalization or nursing home residence, and serious medical conditions. Risk of cardiovascular death associated with azithromycin vs amoxicillin exposure was calculated after controlling for confounding factors using a propensity score. Data were analyzed from December 1, 2016, to March 30, 2020.
Outpatient prescription of azithromycin or amoxicillin.
The primary outcomes were cardiovascular death and sudden cardiac death. An a priori subgroup analysis quantified the effects of azithromycin exposure among patients with increased baseline cardiovascular risk. The secondary outcomes were noncardiovascular death and all-cause mortality.
The study included 7 824 681 antibiotic exposures, including 1 736 976 azithromycin exposures (22.2%) and 6 087 705 amoxicillin exposures (77.8%), among 2 929 008 unique individuals (mean [SD] age, 50.7 [12.3] years; 1 810 127 [61.8%] women). Azithromycin was associated with a significantly increased hazard of cardiovascular death (hazard ratio [HR], 1.82; 95% CI, 1.23-2.67) but not sudden cardiac death (HR, 1.59; 95% CI, 0.90-2.81) within 5 days of exposure. No increases in risk were found 6 to 10 days after exposure. Similar results were observed in patients within the top decile of cardiovascular risk (HR, 1.71; 95% CI, 1.06-2.76). Azithromycin was also associated with an increased risk of noncardiovascular death (HR, 2.17; 95% CI, 1.44-3.26) and all-cause mortality (HR, 2.00; 95% CI, 1.51-2.63) within 5 days of exposure.
These findings suggest that outpatient azithromycin use was associated with an increased risk of cardiovascular death and noncardiovascular death. Causality cannot be established, particularly for noncardiovascular death, owing to the likelihood of residual confounding.
阿奇霉素是美国最常用的抗生素之一。一些观察性研究表明，它与心血管死亡风险增加有关。
与未发现会增加心血管事件的抗生素阿莫西林相比，评估门诊使用阿奇霉素后心血管和心源性猝死的相对和绝对风险。
设计、地点和参与者：这项回顾性队列研究纳入了 2 个大型、多样化的社区综合医疗服务提供系统，全面记录了从 1998 年 1 月 1 日至 2014 年 12 月 31 日的就诊和处方信息。该队列纳入了年龄在 30 至 74 岁之间、在抗生素暴露前至少有 12 个月健康计划覆盖的患者。排除标准为无处方权益、在 10 天内开出 1 种以上研究抗生素、住院或疗养院居住以及患有严重的医疗状况。使用倾向评分控制混杂因素后，计算阿奇霉素与阿莫西林暴露相关的心血管死亡风险。数据分析于 2016 年 12 月 1 日至 2020 年 3 月 30 日进行。
门诊开出阿奇霉素或阿莫西林处方。
主要结局为心血管死亡和心源性猝死。一个事先确定的亚组分析量化了基线心血管风险增加的患者中阿奇霉素暴露的影响。次要结局是非心血管死亡和全因死亡率。
该研究纳入了 7824681 例抗生素暴露，包括 1736976 例阿奇霉素暴露（22.2%）和 6087705 例阿莫西林暴露（77.8%），涉及 2929008 名个体（平均[标准差]年龄 50.7[12.3]岁；1810127[61.8%]为女性）。阿奇霉素与心血管死亡的风险显著增加相关（风险比[HR]，1.82；95%置信区间[CI]，1.23-2.67），但在暴露后 5 天内与心源性猝死无关（HR，1.59；95%CI，0.90-2.81）。在暴露后 6 至 10 天未发现风险增加。在心血管风险最高的十分位数的患者中也观察到了类似的结果（HR，1.71；95%CI，1.06-2.76）。阿奇霉素还与暴露后 5 天内非心血管死亡（HR，2.17；95%CI，1.44-3.26）和全因死亡率（HR，2.00；95%CI，1.51-2.63）的风险增加相关。
这些发现表明，门诊使用阿奇霉素与心血管死亡和非心血管死亡风险增加有关。由于存在残留混杂的可能性，不能确定因果关系，尤其是对于非心血管死亡。
