Ways to increase freedom from DOAC-dependent complications in elderly patients with polypharmacy and chronic kidney disease: molecular and genetic aspects

Introduction. Thanks to advances in modern medicine, it has been possible to significantly increase life expectancy. With the high effectiveness of methods for diagnosing and treating many chronic pathologies, a sharp increase in the number of elderly patients is expected. This cohort of patients has features including polymorbidity; polypharmacy, and low compliance. Taking direct oral anticoagulants (DOACs) is associated with a risk of hemorrhagic complications, which can be difficult to predict in elderly patients, especially those with impaired renal function. Objective. To evaluate factors that increase the risk of taking direct oral anticoagulants in elderly patients with polypharmacy and chronic kidney disease based on the analysis of molecular and genetic markers. Material and methods. For this study, a database was collected that included 503 patients observed at the Moscow State Budgetary Healthcare Institution “Hospital for War Veterans No.2 of the Moscow City Healthcare Department” for the period from April to September 2023 with atrial fibrillation and stage 2C–4C kidney disease. The questionnaire method was used, as well as the collection of clinical and laboratory data to evaluate DOAC-dependent complications – cases of bleeding, duration of DOAC administration. Additionally, molecular markers of endothelial dysfunction and inflammation were determined, as well as genetic polymorphisms associated with DOAC metabolism in kidney tissues. Results. DOAC administration increases bleeding risks with a significant decrease in creatinine clearance (less than 45 ml/min/1.73m2), especially with dabigatran. This observation regarding dabigatran applied to patients in CKD stages C2 and C3a; with creatinine clearance less than 45 ml/min/1.73 m2, this drug was rarely used. The use of apixaban and rivaroxaban does not have a statistically significant increase in the incidence of hemorrhagic complications as renal failure progresses. A correlation was found between the level of molecular markers of endothelial dysfunction (eNOS, VEGF) and the risk of developing DOAC-dependent bleeding. Patients with the rs2032582 single nucleotide polymorphism of the ABCB1 (MDR1) gene had an increased risk of hemorrhagic complications when taking dabigatran. Conclusion. The study of drug interactions and the association of DOAC intake with various endpoints in larger samples will help identify molecular and genetic predictors of adverse outcomes and adjust therapy. A personalized approach to DOAC prescription based on the assessment of kidney function, molecular markers of endothelial dysfunction, and the patient's genetic profile can significantly reduce the risk of hemorrhagic complications in geriatric patients.