Effect of polypharmacy on bleeding with rivaroxaban versus vitamin K antagonist for treatment of venous thromboembolism.

Autor: Bistervels IM; Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Bavalia R; Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Gebel M; Bayer HealthCare, Wuppertal, Germany., Lensing AWA; Bayer HealthCare, Wuppertal, Germany., Middeldorp S; Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.; Radboud University Medical Center, Department of Internal Medicine & Radboud Institute of Health Sciences (RIHS), Nijmegen, The Netherlands., Prins MH; Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, The Netherlands., Coppens M; Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2022 Jun; Vol. 20 (6), pp. 1376-1384. Date of Electronic Publication: 2022 Mar 27.
DOI: 10.1111/jth.15692
Abstrakt: Background: Polypharmacy, including use of inhibitors of CYP3A4 and P-glycoprotein (P-gp), is common in patients with venous thromboembolism (VTE) and is associated with increased bleeding.
Methods: In 8246 patients included in the EINSTEIN-VTE studies for acute VTE, we evaluated the effect of polypharmacy on bleeding and on the relative differences between rivaroxaban and enoxaparin/vitamin K antagonist (VKA). We assessed the incidence of clinically relevant bleeding (major and clinically relevant nonmajor bleeding) by number of comedications (none, 1-3, ≥4) at baseline, and by use of CYP3A4 and/or P-gp inhibitors. Interaction between rivaroxaban versus enoxaparin/VKA and comedication was assessed by Cox regression analysis with p interaction estimates.
Results: With increasing number of comedications, the incidence of clinically relevant bleeding rose from 5.7% to 13.3% in rivaroxaban recipients and from 9.1% to 11.1% in enoxaparin/VKA recipients. Whereas rivaroxaban was associated with a reduced bleeding risk compared with enoxaparin/VKA in patients without comedication (hazard ratio [HR] 0.6, 95% confidence interval [CI] 0.4-0.9), the risk was similar in patients with ≥4 comedications (HR 1.2, 95% CI 0.97-1.5, p interaction .002). Use of CYP3A4 and/or P-gp inhibitors was associated with a doubled bleeding risk compared with no use, without a difference between rivaroxaban and enoxaparin/VKA.
Conclusion: We conclude that fixed-dose rivaroxaban as compared with enoxaparin followed by dose-adjusted VKA is not associated with an increased bleeding risk in patients with VTE administered polypharmacy in general and CYP3A4 and/or P-gp inhibitors specifically. This implies that the observed increased bleeding risks with polypharmacy and use of CYP3A4 and/or P-gp inhibitors are likely explained by comorbidities and frailty, and not by pharmacokinetic interactions.
(© 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)
Databáze: MEDLINE
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