Pharmacogenetics of Bleeding and Thromboembolic Events in Direct Oral Anticoagulant Users

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Lähteenmäki , J , Vuorinen , A-L , Pajula , J , Harno , K , Lehto , M , Niemi , M & Gils , M V 2021 , ' Pharmacogenetics of Bleeding and Thromboembolic Events in Direct Oral Anticoagulant Users ' , Clinical Pharmacology and Therapeutics , vol. 110 , no. 3 , pp. 768-776 . https://doi.org/10.1002/cpt.2316

Title: Pharmacogenetics of Bleeding and Thromboembolic Events in Direct Oral Anticoagulant Users
Author: Lähteenmäki, Jaakko; Vuorinen, Anna-Leena; Pajula, Juha; Harno, Kari; Lehto, Mika; Niemi, Mikko; Gils, Mark van
Contributor organization: University of Helsinki
HUS Heart and Lung Center
Staff Services
HUSLAB
Department of Clinical Pharmacology
Department of Diagnostics and Therapeutics
INDIVIDRUG - Individualized Drug Therapy
HUS Diagnostic Center
Date: 2021-09
Language: eng
Number of pages: 9
Belongs to series: Clinical Pharmacology and Therapeutics
ISSN: 0009-9236
DOI: https://doi.org/10.1002/cpt.2316
URI: http://hdl.handle.net/10138/340484
Abstract: This study aimed to analyze associations between genetic variants and the occurrence of clinical outcomes in dabigatran, apixaban, and rivaroxaban users. This was a retrospective real-world study linking genotype data of three Finnish biobanks with national register data on drug dispensations and healthcare encounters. We investigated several single-nucleotide variants (SNVs) in the ABCG2, ABCB1, CES1, and CYP3A5 genes potentially associated with bleeding or thromboembolic events in direct oral anticoagulant (DOAC) users based on earlier research. We used Cox regression models to compare the incidence of clinical outcomes between carriers and noncarriers of the SNVs or haplotypes. In total, 1,806 patients on apixaban, dabigatran, or rivaroxaban were studied. The ABCB1 c.3435C>T (p.Ile1145=, rs1045642) SNV (hazard ratio (HR) 0.42, 95% confidence interval (CI), 0.18-0.98, P = 0.044) and 1236T-2677T-3435T (rs1128503-rs2032582-rs1045642) haplotype (HR 0.44, 95% CI, 0.20-0.95, P = 0.036) were associated with a reduced risk for thromboembolic outcomes, and the 1236C-2677G-3435C (HR 2.55, 95% CI, 1.03-6.36, P = 0.044) and 1236T-2677G-3435C (HR 5.88, 95% CI, 2.35-14.72, P < 0.001) haplotypes with an increased risk for thromboembolic outcomes in rivaroxaban users. The ABCB1 c.2482-2236G>A (rs4148738) SNV associated with a lower risk for bleeding events (HR 0.37, 95% CI, 0.16-0.89, P = 0.025) in apixaban users. ABCB1 variants are potential factors affecting thromboembolic events in rivaroxaban users and bleeding events in apixaban users. Studies with larger numbers of patients are warranted for comprehensive assessment of the pharmacogenetic associations of DOACs and their relevance for clinical practice.
Subject: ATRIAL-FIBRILLATION
GENE POLYMORPHISMS
PLASMA-LEVELS
ABCB1
DABIGATRAN
IMPACT
APIXABAN
RS4148738
REGISTER
QUALITY
317 Pharmacy
Peer reviewed: Yes
Rights: cc_by_nc
Usage restriction: openAccess
Self-archived version: publishedVersion


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