Key result
Rivaroxaban Css min >137 pg/mL linked to ~494% higher major bleeding risk in ACS and AF.
Why the study?
The study sought to evaluate the effects of pharmacokinetic and pharmacogenetic factors on major bleeding in patients with ACS and non-valvular AF receiving combined antithrombotic therapy.
Do pharmacokinetic and pharmacogenetic factors predict major bleeding in patients with ACS and AF receiving combined antithrombotic therapy?
Observational (n=100)
Yes
Do pharmacokinetic and pharmacogenetic factors predict major bleeding in patients with ACS and AF receiving combined antithrombotic therapy?
Measuring residual steady-state rivaroxaban concentrations and determining ABCB1 rs4148738 polymorphism carriage may help identify high-risk ACS patients with AF who could benefit from antithrombotic therapy modification to prevent major bleeding.
Answers are grounded in this paper and cite their sources.
Residual rivaroxaban levels were associated with major bleeding in ACS/AF; hypothesis-generating for concentration-guided dosing pending prospective validation.
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 < 0.004)) and carriage of the T allelic variant polymorphism ABCB1 rs4148738 (8.97 OR (95% CI, 1.48–14.49; p < 0.017)), as well as for the BARC scale (5.76 OR (95% CI, 2.36–9.87; p < 0.018)). 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.
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Baturina et al. (2023) conducted an observational in Acute Coronary Syndrome and Atrial Fibrillation (n=100). Rivaroxaban Css min >137 pg/mL and ABCB1 rs4148738 T allele was evaluated on Major bleeding events based on the ISTH scale (OR 5.94, 95% CI 3.13-12.99, p=<0.004). A rivaroxaban Css min >137 pg/mL was significantly associated with increased major bleeding (OR 5.94; 95% CI 3.13-12.99; p<0.004) in ACS and AF patients on combined antithrombotic therapy.
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