Direct oral anticoagulants (DOACs) plus clarithromycin associated with higher risk of bleed than DOACs plus azithromycin

Référence

Hill K, Sucha E, Rhodes E, et al. Risk of hospitalization with hemorrhage among older adults taking clarithromycin vs. azithromycin and direct oral anticoagulants. JAMA Intern Med 2020;180(8):1052-1060.

Sommaire

Pharmacokinetic studies have shown that clarithromycin used concurrently with DOACs leads to increased serum levels of DOACs and prolongation of coagulation time. The same effect is not seen with azithromycin. Whether the combined use of clarithromycin and a DOAC leads to increased bleeding in the clinical setting is unknown. In this Ontario-based study, investigators used multiple national databases to find adults older than 65 years who had received a new prescription for a DOAC (apixaban, dabigatraban, or rivaroxaban) and then identified a subset of these patients who also received a prescription for clarithromycin or azithromycin. Of the 24,943 patients in this cohort, 6592 (26.4%) received clarithromycin and 18,351 (73.6%) received azithromycin. The 2 groups were similar except for proton pump inhibitor use, mean daily DOAC dose, and DOAC type. The most commonly prescribed DOAC was rivaroxaban (40.0%). The primary outcome was a major hemorrhage, such as gastrointestinal bleeds and nontraumatic intracranial bleeds, requiring hospital admission or emergency department visit up to 30 days after the dispensing of clarithromycin or azithromycin. As compared with patients who were prescribed azithromycin, patients in the clarithromycin group were more likely to experience a major bleed (0.77% vs. 0.43%; adjusted hazard ratio 1.71; 95% CI 1.20 - 2.45). The higher rate of bleeds also occurred when comparing periods of clarithromycin use with periods of nonuse in individuals.