Oral anticoagulants in the prevention of thromboembolic complications in cardiac patients: analysis of use in the Russian Federation

Abstract

In last years, special attention has been paid in the Russian Federation (RF) to improving medical care for patients with atrial fibrillation (AF) and the prevention of thromboembolic complications (TEC). The appearance on the Russian market of new oral anticoagulants (NOAC) has become a help for doctors, however, their cost imposes restrictions on the use. A humanitarian aid drugs to medical organizations of the RF, an active information program from manufacturers over the past 1.5 years have significantly increased the use of NOAC. In different regions, a different situation arises regarding the procurement and frequency of use of one or another anticoagulant. Analyzing the procurement of additional drug supplies for different regions of the Russian Federation, we see that dabigatran is preferred in a number of regions of the Central Federal District, and rivaroxaban in the Northern regions. The cost of warfarin is low. Data on the important role of the genotype in determining the individual dose and the development of bleeding, which is associated with the metabolism of warfarin, have been obtained. The pharmacogenetic approach allows you to quickly and efficiently choose its dose. The use of generics is highly relevant on the Russian market. Also, a number of regions are of great interest as a basis for conducting clinical trials of drugs. Aim. To analyze the current use of anticoagulant drugs taking into account personalized treatment approaches (the implementation of pharmacogenetic examinations and the work of anticoagulation clinics). Methods. Analysis of real clinical practice in the Russian Federation, patient registries, evaluation of adverse events in anticoagulation therapy and pharmacogenetic studies. Analysis of anticoagulant purchase under the Drug Reimbursement Program in several regions of the RF. Evaluation of the effect of anticoagulation clinics throughout the RF. Results. We analyzed the use of anticoagulants. To reduce the risk of thromboembolic complications and select the appropriate antithrombotic therapy, the entire range of antithrombotic agents is required, including NOACs and vitamin K antagonists (warfarin). Th e appearance of warfarin and NOACs on the Russian market has significantly improved the quality of medical care and treatment outcomes in these patients. Active awareness raising, the addition of anticoagulants to the national clinical guidelines and to clinical practice, and state support as part of the Drug Reimbursement Program have significantly increased the frequency of anticoagulant use. Nevertheless, the frequency of anticoagulant use varies slightly between regions. Warfarin is the most widely used anticoagulant and has high affordability (from 44 to 72.5 % out of all anticoagulants). The frequency of bleeding does not differ significantly between different anticoagulants, with an average of 2.8 %. A first INR value of ≥2.0 aft er 3-5 days is significantly associated with over coagulation during warfarin dose titration. The rapid achievement of an anticoagulation effect is often associated with a specific genotype (CYP2C9*2/*2, *3/*3 and 2/*3 variants and A/A of the VKORC1 gene, or CYP2C9 and VKORC1 polymorphism). Pharmacogenomics-guided warfarin dosing in clinical practice allows the warfarin dose to be selected in a faster and more effective way and for the risk of adverse reactions to be reduced. The creation of a network of anticoagulation clinics has proven to be highly effective. The most well-structured system of anticoagulation clinics is present in the Kursk Region. Rivaroxaban was the biggest selling anticoagulant out of the NOACs on the Russian sales market in 2018, but given the growth in apixaban sales, it is likely that this NOAC will move into first place in the near future.Conclusion. A personalized approach to anticoagulant use is crucial for the prevention of thromboembolic complications.