Abstract Number: PB1719
Meeting: ISTH 2020 Congress
Background: The direct oral anticoagulants (DOACs) have growing utility in patients with atrial fibrillation (AF) and venous thromboembolic disorders. Major bleeding and thrombotic complications occur in 1-3% of patients. A number of enzymes including CYP450 contribute to the absorption and metabolism of DOACs. CYP450 activity varies among individuals and is susceptible to inhibition and induction via drug-drug interactions. Utilizing pharmacogenomics (PGx) in DOACs dosing may lead to lower bleeding and thrombotic complications.
Aims: We evaluated the association of bleeding and thrombosis complications in subjects on DOACs with specific pharmacogenomics variations.
Methods: We analyze pharmacogenomics data of subjects enrolled in the “Right 10k Study” and on one of the DOACs.
Results: There are 10,036 patients with baseline PGx data enrolled in the Mayo Clinic “Right10k Study”. 294 patients used DOACs, mean age was 73, and 46.9% were female. 66.3 % (195/294) used apixaban, 33.7% (99/294) used rivaroxaban, and 7.1% (21/294) used dabigatran. 21 patients used more than 1 DOAC over the course of treatment for the qualifying condition. AF was the most common indication for DOAC use (71.8%). There were (46) subjects experienced bleeding and (39) have thrombotic complications. Among bleeding complications, 19 developed GI bleeding, 6 developed intracranial hemorrhage, and the remainder had clinically relevant nonmajor bleeding. Among thrombotic complications, 20 developed DVTs/PEs, 4 superficial thromboses, and the remainder were strokes/TIAs. No significant differences with respect to age, gender, DOAC, cancer history were seen between those without complication while on therapy. Chronic kidney disease (CKD) stage 3 or greater was associated with significantly higher rates of bleeding (p=0.018).
Conclusions: Patient genotype was not associated with increased risk of bleeding or thrombotic complications while on DOACs. Patients with CKD were significantly more likely to have major bleeding on DOACs.
|Phenotype||No complications||Bleeding and Thrombotic complications||Total||Chi-Square P value|
|CYP3A4_Phenotype Normal (extensive) metabolizer||192 (86.9%)||68 (93.2%)||260 (88.4%)||0.1712|
|Warfarin sensitivity Phenotype||68 (30.8%)||25 (34.2%)||93 (31.6%)||0.9287|
|CYP2C19_Phenotype Decreased function||44 (19.9%)||17 (23.3%)||61 (20.7%)||0.2526|
|CYP2C9_Phenotype Normal (extensive) metabolizer||133 (60.2%)||43 (58.9%)||176 (59.9%)||0.4721|
|CYP1A2_Phenotype Rapid metabolizer||194 (87.8%)||66 (90.4%)||260 (88.4%)||0.6011|
|CYP3A5_Phenotype Poor metabolizer||192 (86.9%)||63 (86.3%)||255 (86.7%)||0.9423|
|CYP2D6_Phenotype Normal (extensive) metabolizer||76 (34.4%)||23 (31.5%)||99 (33.7%)||0.5665|
|SLCO1B1_Phenotype Decreased function||44 (19.9%)||17 (23.3%)||61 (20.7%)||0.1185|
|UGT1A1_Phenotype Normal (extensive) metabolizer||109 (49.3%)||32 (43.8%)||141 (48.0%)||0.0819|
[DOACs Pharmacogenomics phenotype]
To cite this abstract in AMA style:Schekel C, Shamoun F, Abdelmalek M, Wang J, Girardo M, Kusne Y. DOAC Pharmacogenomics: Personalized Therapeutics to Avoid Bleeding and Thrombotic Complications [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/doac-pharmacogenomics-personalized-therapeutics-to-avoid-bleeding-and-thrombotic-complications/. Accessed January 27, 2022.
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