The possibilities of improving the clinical use of direct oral anticoagulants

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Abstract

Background. More than 40 million people worldwide suffer from atrial fibrillation. Atrial fibrillation is often combined with chronic heart failure (CHF). All patients with atrial fibrillation and CHF, regardless of the left ventricular ejection fraction, are prescribed anticoagulants. Direct oral anticoagulants (DOACs) apixaban and rivaroxaban are widely used in patients with atrial fibrillation. However, to date, there is very little data comparing these two drugs.

Aims — сomparative evaluation of the clinical efficacy and safety profile of DOACs (apixaban and ravaroxaban) in patients based on real clinical practice data.

Methods. The study materials were based on the results of the analysis of commercial data on the use of DOACs (apixaban, rivaroxaban) from the depersonalized Optum Clinformatics Data Mart database for the period from January 1, 2013 to December 31, 2020. The primary efficacy indicator was a comprehensive indicator of ischemic stroke. The primary safety indicator was a comprehensive indicator of gastrointestinal bleeding. Information on adverse reactions was obtained from a specialized website VigiAccess (http://www.vigiaccess.org). As an analytical tool, attribute statistics methods were used to determine the risk of developing a particular condition against the background of using the analyzed drug relative to the comparison drug.

Results. During the analysis of two compared drugs (rivaroxaban versus apixaban), the following values of statistical parameters were obtained: AR — 0.3% (95% CI: 0.08–0.52%); OR — 1.61 (95% CI: 0.43–2.80); PAR — 0.15% (95% CI: 0.03–0.34%). The use of rivaroxaban increases the likelihood of developing ischemic stroke compared to the use of apixaban by 0.15% in the entire population. According to the electronic resource VigiAccess, 174,234 reports of adverse events were identified for apixaban (as of 16.07.2025), and 177,285 similar reports for rivaroxaban as of the same date. Circulatory disorders were noted in the total number of reports in 7% of cases for apixaban, and in 9% for rivaroxaban. Apixaban and rivaroxaban are substrates of both CYP3A4 and P-glycoprotein (P-gp). Coadministration with CYP3A4 and P-gp inhibitors increases plasma concentrations of DOACs and increases the risk of bleeding. Coadministration with CYP3A4 and P-gp inducers decreases plasma concentrations of DOACs and increases the risk of thrombosis and thromboembolic events.

Conclusions. Apixaban and rivaroxaban demonstrate similar efficacy in relation to the primary goal — prevention of stroke and thrombosis. The safety and efficacy of therapy with OPA is determined by optimizing the choice of drug and its dose, taking into account possible drug interactions, and dose adjustment in case of liver and kidney dysfunction.

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About the authors

Olga V. Zhukova

Plekhanov Russian University of Economics; Privolzhsky Research Medical University

Author for correspondence.
Email: ov-zhukova@mail.ru
ORCID iD: 0000-0002-6454-1346
SPIN-code: 4167-1496

PhD in Pharmacology, Assistant Professor

Russian Federation, Moscow; Nizhny Novgorod

Nikolay L. Shimanovsky

Plekhanov Russian University of Economics; Pirogov Russian National Research Medical University (Pirogov Medical University)

Email: shimann@yandex.ru
ORCID iD: 0000-0001-8887-4420
SPIN-code: 5232-8230

MD, PhD, Professor, Corresponding Member of the RAS

Russian Federation, Moscow; Moscow

Valery V. Beregovykh

Russian Academy of Sciences

Email: beregovykh@ramn.ru
ORCID iD: 0000-0002-0210-4570
SPIN-code: 5940-7554

PhD in Technical Sciences, Professor, Academician of the RAS

Russian Federation, Moscow

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