june 2020 • JAMA Internal Medicine

Risk of Hospitalization With Hemorrhage Among Older Adults Taking Clarithromycin vs Azithromycin and Direct Oral Anticoagulants

Hill K, Sucha E, Rhodes E, et al.

DOI: 10.1001/jamainternmed.2020.1835

Content curated by::David Silvério Rodrigues

Key message

Estudo que tenta responder à pergunta se o uso simultâneo de claritromicina em pessoas idosas que tomam anticoagulantes orais está associado a maior risco de hospitalização por hemorragia em comparação com a azitromicina?Encontraram que neste estudo de coorte em nível populacional de 24943 idosos utilizadores de anticoagulantes orais diretos, a claritromicina foi associada a uma taxa ajustada de hospitalização por hemorragia relevante de 1,71 vezes maior (diferença de risco absoluta, 0,34%) em comparação com a azitromicina .Conclui-se que o uso de claritromicina foi associado a uma maior taxa de hemorragia entre os idosos que tomam anticoagulantes orais diretos em comparação com a azitromicina pelo que poderemos estar perante uma potencial e importante interação medicamentosa.

Abstract

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.