Abstract Number: PB1719
Meeting: ISTH 2020 Congress
Theme: Platelets and Megakaryocytes » Platelet Proteomics and Genomics
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.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/doac-pharmacogenomics-personalized-therapeutics-to-avoid-bleeding-and-thrombotic-complications/