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Risk of major bleeding among users of direct oral anticoagulants combined with interacting drugs: A population‐based nested case–control study
Author(s) -
Zhang Yumao,
Souverein Patrick C.,
Gardarsdottir Helga,
Ham Hendrika A.,
Maitlandvan der Zee AnkeHilse,
Boer Anthonius
Publication year - 2020
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.14227
Subject(s) - medicine , nested case control study , rivaroxaban , odds ratio , dabigatran , apixaban , confidence interval , pharmacodynamics , warfarin , population , rotterdam study , pharmacokinetics , atrial fibrillation , environmental health
Aims To assess the association between concurrent use of potential pharmacokinetic or pharmacodynamic interacting drugs and major bleeding among direct oral anticoagulant (DOAC) users. Methods We performed a case–control study nested in a cohort of new users of DOACs (dabigatran etexilate, apixaban or rivaroxaban). Data were obtained from the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics (2008–2015). Cases were patients hospitalized having a primary diagnosis of major bleeding. Up to 4 controls were matched on age, sex, index date and region. Odds ratios (ORs) for the risk of major bleeding were assessed by conditional logistic regression analysis and adjusted for well‐known covariates for the risk of bleeding. Results We identified 393 patients with a major bleeding from a total of 23 492 new users of DOACs and 1494 matched controls. Most subjects were users of rivaroxaban (58.8%) on the index date. The concurrent use of pharmacodynamic interacting drugs was associated with an increased risk of major bleeding (21.6% of cases vs 13.5% of controls, adjusted odds ratio [aOR] 1.92; 95% confidence interval [CI], 1.40–2.66). For the antiplatelet drugs the aOR was 2.01 (95% CI, 1.29–3.11) and for the selective serotonin reuptake inhibitors the aOR was 1.68 (95% CI, 1.10–2.59). We found no increased risk of major bleeding for concurrent use of pharmacokinetic interacting drugs vs DOACs alone (45.0 vs 51.2%; aOR: 0.77; 95% CI: 0.53–1.10). Conclusion Among patients taking DOACs the concurrent use of antiplatelet drugs or selective serotonin reuptake inhibitors was associated with increased risk of major bleeding, while pharmacokinetic interacting drugs do not increase this risk.