老年人使用克拉霉素与阿奇霉素和直接口服抗凝剂治疗时发生出血住院的风险。
Risk of Hospitalization With Hemorrhage Among Older Adults Taking Clarithromycin vs Azithromycin and Direct Oral Anticoagulants.
机构信息
Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
出版信息
JAMA Intern Med. 2020 Aug 1;180(8):1052-1060. doi: 10.1001/jamainternmed.2020.1835.
IMPORTANCE
Clarithromycin is a commonly prescribed antibiotic associated with higher levels of direct oral anticoagulants (DOACs) in the blood, with the potential to increase the risk of hemorrhage.
OBJECTIVE
To assess the 30-day risk of a hospital admission with hemorrhage after coprescription of clarithromycin compared with azithromycin among older adults taking a DOAC.
DESIGN, SETTING, AND PARTICIPANTS: This population-based, retrospective cohort study was conducted among adults of advanced age (mean [SD] age, 77.6 [7.2] years) who were newly coprescribed clarithromycin (n = 6592) vs azithromycin (n = 18 351) while taking a DOAC (dabigatran, apixaban, or rivaroxaban) in Ontario, Canada, from June 23, 2009, to December 31, 2016. Cox proportional hazards regression was used to examine the association between hemorrhage and antibiotic use (clarithromycin vs azithromycin). Statistical analysis was performed from December 23, 2019, to March 25, 2020.
MAIN OUTCOMES AND MEASURES
Hospital admission with major hemorrhage (upper or lower gastrointestinal tract or intracranial). Outcomes were assessed within 30 days of a coprescription.
RESULTS
Among the 24 943 patients (12 493 women; mean [SD] age, 77.6 [7.2] years) in the study, rivaroxaban was the most commonly prescribed DOAC (9972 patients [40.0%]), followed by apixaban (7953 [31.9%]) and dabigatran (7018 [28.1%]). Coprescribing clarithromycin vs azithromycin with a DOAC was associated with a higher risk of a hospital admission with major hemorrhage (51 of 6592 patients [0.77%] taking clarithromycin vs 79 of 18 351 patients [0.43%] taking azithromycin; adjusted hazard ratio, 1.71 [95% CI, 1.20-2.45]; absolute risk difference, 0.34%). Results were consistent in multiple additional analyses.
CONCLUSIONS AND RELEVANCE
This study suggests that, among adults of advanced age taking a DOAC, concurrent use of clarithromycin compared with azithromycin was associated with a small but statistically significantly greater 30-day risk of hospital admission with major hemorrhage.
重要性
克拉霉素是一种常用的抗生素，与血液中直接口服抗凝剂（DOAC）水平升高有关，可能增加出血风险。
目的
评估与阿奇霉素相比，在服用 DOAC 的老年人中同时使用克拉霉素与 30 天内因出血而住院的风险。
设计、地点和参与者：这是一项基于人群的回顾性队列研究，纳入了 2009 年 6 月 23 日至 2016 年 12 月 31 日期间在加拿大安大略省新同时服用 DOAC（达比加群、阿哌沙班或利伐沙班）的年龄较大的成年人（平均[SD]年龄 77.6[7.2]岁），这些成年人被新处方了克拉霉素（n=6592）或阿奇霉素（n=18351）。使用 Cox 比例风险回归来检查出血与抗生素使用（克拉霉素与阿奇霉素）之间的关联。统计分析于 2019 年 12 月 23 日至 2020 年 3 月 25 日进行。
主要结局和测量
因大出血（上或下胃肠道或颅内）而住院。在处方后的 30 天内评估结果。
结果
在 24943 名患者（12493 名女性；平均[SD]年龄 77.6[7.2]岁）中，利伐沙班是最常用的 DOAC（9972 名患者[40.0%]），其次是阿哌沙班（7953 名[31.9%]）和达比加群（7018 名[28.1%]）。与 DOAC 同时使用克拉霉素而非阿奇霉素与因大出血而住院的风险较高相关（服用克拉霉素的 6592 名患者中有 51 名[0.77%]，服用阿奇霉素的 18351 名患者中有 79 名[0.43%]；调整后的危险比，1.71[95%CI，1.20-2.45]；绝对风险差异，0.34%）。在多项额外分析中，结果一致。
结论和相关性
这项研究表明，在服用 DOAC 的年龄较大的成年人中，与阿奇霉素相比，同时使用克拉霉素与 30 天内因大出血而住院的风险略有但统计学上显著增加相关。
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