Abstract 14321: Dabigatran-Associated Bleedings May Result From Pharmacokinetic Interactions With Mild P-gp Inhibitors in Very Elderly Patients

• Published in: Circulation (New York, N.Y.) N.Y.), 2019-11, Vol.140 (Suppl_1 Suppl 1), p.A14321-A14321
• Main Authors: Bernier, Marjorie, Parassol, Nadege, Lavrut, Thibaud, Drici, Milou-Daniel
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.140.suppl_1.14321

IntroductionAFib shall concern more than half of the very elderly population by 2050. The benefit risk ratio of anticoagulants must thereforebe optimized in this population. Direct oral anticoagulants do not require any routine therapeutic drug monitoring. Yet, concerns about their inherent bleeding risk, especially in very elderly, patients are under scrutiny at the EMA level in normal conditions of use.HypothesisWe aimed to evaluate whether the co-prescription of mild P-gp inhibitors commonly prescribed during AFib might increase dabigatran plasma level and yield bleeding complications, in usual conditions of care of the very elderly.MethodsSixty very elderly patients (>85 years-old) with non valvular AFib receiving dabigatran were included in a prospective cohort. Prescriptions were screened for the presence (Group A) or not (Group B) of P-gp inhibitors. Dabigatran plasma levels were measured by HPLC couple to tandem mass spectrometry. Plasma concentrations were deemed as normal (95th percentile).Resultspatients from Group A had increased mean dabigatran plasma concentrations as compared with patients from Group B (190 ± 112 ng/ml vs 93 ± 54 ng/ml respectively). About a third of the patients from Group A had concentrations deemed “out of range” (> 95 percentile of peak and trough concentrations of the RE-LY pivotal study) versus none in Group B (p=0.05). This was associated with more frequent bleeding complications in Group A (A30.4%) as compared with group B8.6%, p = 0.04). The main co-prescription of concern in term of mild P-gp antagonists was amiodarone (all, but one case with verapamil).Conclusionsco-prescription of dabigatran in usual conditions of care with mild P-gp inhibitors such as amiodarone or verapamil yields higher dabigatran plasma concentrations and more frequent bleeding occurrences in the very elderly patient. Therapeutic drug monitoring in this population might not then be superfluous.