Association between Use of Pharmacokinetic-Interacting Drugs and Effectiveness and Safety of Direct Acting Oral Anticoagulants: Nested Case-Control Study

Clin Pharmacol Ther. 2021 Jul 19. doi: 10.1002/cpt.2369. Online ahead of print.ABSTRACTConcomitant use of direct oral anticoagulants (DOACs) and medications with inhibition/induction effect on P-gp/CYP3A might increase risk of bleeding/treatment failure, respectively. We designed a nested case-control study within a Clalit cohort of atrial fibrillation (AF) patients and a cohort of venous thromboembolic patients, new users of a DOAC (1.1.2010-24.8.2020). Propensity scores were constructed from demographic, clinical and medications at cohort entry. Each case of: 1) serious bleeding event; 2) stroke/systemic emboli (SE) in AF patients; 3) recurrent thromboembolism in thromboembolic patients, was matched by age, sex, length of follow up, year of cohort entry, DOAC type, and DOAC indication, to up to 20 controls. Within 89284 AF and venous thromboembolic patients and 126,302 patient-years of follow up, there were 1587 serious bleeding events. Risk of serious bleeding increased in association with concurrent prescription of P-gp/CYP3A4 inhibitors. Specifically, higher bleeding risk was associated with dabigatran-verapamil, rivaroxaban-verapamil, and rivaroxaban-amiodarone concurrent prescriptions: adjusted ORs 2.29 (1.13-4.60), 2.18 (1.07-4.40), 1.68 (1.14-2.49), respectively. There were 1116 events of stroke/SE, in 79302 DOAC-treated AF patients and 118,124 patient-years of follow up. Concomitant use of phenytoin, carbamazepine, valproic acid, or levetiracetam was associated with...
Source: Clinical Pharmacology and Therapeutics - Category: Drugs & Pharmacology Authors: Source Type: research