O. A. Panibratiuk, O. А. Yakovleva

National Pirogov Memorial Medical University, Vinnytsya, Ukraine;
e-mail: olaynauka@gmail.com

Received: 26 February 2020; Accepted: 30 June 2020

In this research work we examined the effect of various factors on the efficacy and safety of warfarin pharmacotherapy. Particular emphasis was placed on drug interaction in the standardized treatment of patients with coronary heart disease and atrial fibrillation. Since the administration of such drugs as digoxin and statins with warfarin leads to an increase in the blood level of all three drugs (they interact at the level of P-glycoprotein) and warfarin has a narrow therapeutic window, the risk of hemorrhagic complications is increased. For the first time in patients of the Podillya region of Ukraine, the genetic polymorphism of cytochrome CYP2C9 was determined, which is associated with the slow withdrawal of anticoagulant from the bloodstream and the possible risk of bleeding. For safe pharmacotherapy, patients were given significantly different doses of warfarin in all comparison groups, according to the International Normalized Ratiо (INR). For example, in the group with a CYP2C9 mutation present, the dose was 3.08 ± 0.25 mg versus 4.15 ± 0.22 mg in the non-mutation group (P = 0.008). In addition, in patients with genetic polymorphism of detoxification enzymes, significantly more bleeding events (light or clinically significant; critical organ bleeding) were observed, but among these patients bleeding occurred at an INR of 2.6 (despite the recommendations of the European Society of Cardiology, that the INR can be maintained within 2.0-3.0). Therefore, patients with CYP2C9 mutations require a personalized approach and control of the INR in a safer range (2.0 to 2.5) and consideration of drug interactions.

Keywords: bleeding on anticoagulation, genetic polymorphism CYP2C9, interaction of warfarin, slow metabolites, warfarin