Pharmacokinetic and Pharmacogenetic Predictors of Major Bleeding Events in Patients with an Acute Coronary Syndrome and Atrial Fibrillation Receiving Combined Antithrombotic Therapy

Abstract

Objective: This study’s objective was to evaluate the effects of pharmacokinetic and pharmacogenetic factors on major bleeding in patients with ACS and non-valvular AF receiving combined antithrombotic therapy consisting of rivaroxaban, clopidogrel, and aspirin as part of dual or triple therapy. Methods: A prospective observational study was conducted in two PCI centers in Moscow, the Russian Federation, from 2017 to 2018. One hundred patients with ACS and AF were enrolled. Prospective follow-ups continued for 12 months. Results: A total of 36 patients experienced bleeding events, with 10 experiencing major bleeding based on the BARC scale and 17 experiencing major bleeding based on the ISTH scale. The following predictors associated with an increased number of major bleeding events were identified: for the ISTH scale, a Css min. of rivaroxaban of >137 pg/mL (5.94 OR, (95% CI, 3.13–12.99; p p p Conclusions: Measuring residual steady-state rivaroxaban concentrations and determining the carriage of the T allelic variant polymorphism ABCB1 rs4148738 may be applicable to high-risk patients for subsequent antithrombotic therapy modification.

Keywords

• combined antithrombotic therapy
• rivaroxaban
• clopidogrel
• dual antiplatelet therapy
• triple antiplatelet therapy
• atrial fibrillation