The Impact of Combination Therapy with Rivaroxaban and Acetylsalicylic Acid in Patients with Coronary Heart Disease on the Achievement of the Target for Reducing Mortality from Cardiovascular Diseases of the Federal Project "Fight against Cardiovascular Diseases"

Aim. To assess the outcomes of combination therapy with rivaroxaban and acetylsalicylic acid (ASA) in patients with stable coronary artery disease (CAD) and a high risk of thrombotic events on the set targets of Ministry of Health for reduction of cardiovascular mortality in Russia.

Material and methods. The development of the model for analysis in MS Excel included the following stages: calculation of the population of patients with stable CAD who can be treated with combination therapy (rivaroxaban and ASA); calculation of the number of deaths due to cardiovascular disease (CVD), number of strokes and myocardial infarction (MI) in the current scenario (patients receive monotherapy with ASA) and simulated scenario (some patients switch from monotherapy to combination therapy); estimation the impact of the number of avoided cases of deaths due to combination therapy on set target for reducing CVD mortality in 2024 year; sensitivity analysis to assess the sustainability of outcomes.

Results. Total number of eligible patients for combination therapy was estimated as 1.08 million patients. Based on the simulation results, it was determined that with the reallocation of patients from monotherapy with ASA to combination therapy with rivaroxaban and ASA, the number of avoided deaths in 2022 will be 973 cases, in 2023 – 1,622 cases, in 2024 – 3,245 cases, which will make it possible to reach 6.7%, 7.4% and 11.1% of the set target for reduction of mortality from CVD in the respective years. In addition, the gradual reallocation of patients from monotherapy to combination therapy might decrease the cases of stroke and MI in 973 and 649 cases by 2022, 1,622 and 1,082 cases by 2023, and 3 245 and 2 163 cases by 2024 year, respectively. Sensitivity analysis showed that outcomes are sustainable.

Conclusion. The use of combination therapy of rivaroxaban and ASA in patients with stable CAD and high thrombotic risk will allow to achieve up to 11.1% of the set target for reduction of mortality from CVD by 2024 in Russia and can also potentially impact on another set target for reduction mortality from cerebrovascular diseases by reducing the number of strokes. Thereby, this therapy can be considered for drug provision programmes for patients with stable CAD and high thrombotic risk to fulfill the goals to reduce mortality from CVD.

1. Roth GA, Mensah GA, Johnson CO, et al. Global burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study. J Am Coll Cardiol. 2020;76(25):2982-3021. DOI:10.1016/j.jacc.2020.11.010.

2. World Health Organization. Cardiovascular diseases (CVDs) [cited 2021 May 12]. Available from: https://www.who.int/en/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds).

3. Federal State Statistics Service. Number of deaths per cause in 2020. [cited 2021 May 12]. Available from: https://rosstat.gov.ru/storage/mediabank/lA0wo9Xm/demo24-2.xlsx (In Russ.)

4. Federal State Statistics Service. Distribution of the number of persons aged 18 and over who are disabled for the first time in 2019 [cited 2021 May 12]. Available from: https://rosstat.gov.ru/folder/13721 (In Russ.)

5. Gheorghe A, Griffiths U, Murphy A, et al. The economic burden of cardiovascular disease and hypertension in low-and middle-income countries: a systematic review. BMC Public Health. 2018;18(1):1-11. DOI:10.1186/s12889-018-5806-x.

6. Mendis S, Puska P, Norrving B. Global Atlas on Cardiovascular Disease Prevention and Control. Geneva: WHO; 2011 [cited 2021 May 12]. Available from: https://apps.who.int/iris/handle/10665/44701.

7. Harvard School of Public Health. A report by the World Economic Forum and the Harvard School of Public Health: The Global Economic Burden of Non-communicable Diseases. [cited 2021 May 12]. Available from: https://www3.weforum.org/docs/WEF_Harvard_HE_GlobalEconomicBurdenNonCommunicableDiseases_2011.pdf.

8. Government Decree of Russian Federation “About approval of state programme “Development of Healthcare” dated 26.12.2017 №1640 [cited 2021 May 12]. Available from: http://www.consultant.ru/document/cons_doc_LAW_286834/ (in Russ.)

9. Government Decree of Russian Federation “About inclusion of changes into state programme “Development of Healthcare” dated 30.11.2019 №1569 [cited 2021 May 12]. Available from: http://publication.pravo.gov.ru/Document/View/0001201912060020 (in Russ.)

10. Order of Ministry of Health of Russian Federation “On approval of the list of drugs for medical use to provide on an outpatient basis to persons who have suffered an acute cerebrovascular accident, myocardial infarction, and who have undergone coronary artery bypass grafting, angioplasty of the coronary arteries with stenting and catheter ablation for cardiovascular diseases” dated 24.09.2021 №936n [cited 2021 Oct 12]. Available from: http://publication.pravo.gov.ru/Document/View/0001202110150031 (In Russ.)

11. Ministry of Health of Russian Federation. Results of 2020. [cited 2021 May 12]. Available from: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/055/642/original/MZRF_2021_All_08-04-2021-Preview.pdf?1619014721 (In Russ.)

12. Government of Russian Federation. Meeting of project committee for national projects “Health care” and “Demography” [cited 2021 May 12]. Available from: http://government.ru/news/41878/ (in Russ.)

13. Government Decree of Russian Federation “About inclusion of changes into state programme “Development of Healthcare” dated 31.03.2021 №512 [cited 2021 May 12]. Available from: http://publication.pravo.gov.ru/Document/View/0001202104070027 (in Russ.)

14. Government Decree of Russian Federation “About inclusion of changes into Application N 10 of state programme “Development of Healthcare” dated 24.07.2021 №1254 [cited 2021 Oct 12]. Available from: http://publication.pravo.gov.ru/Document/View/0001202108020037 (in Russ.)

15. Boytsov SA, Demkina AE, Oshchepkova EV, et al. Progress and Problems of Practical Cardiology in Russia at the Present Stage. Kardiologiia. 2019;59(3):53-9 (In Russ.) DOI:10.18087/cardio.2019.3.10242.

16. Russian Society of Cardiology. Clinical guidelines: Stable coronary artery disease [cited 2021 May 12]. Available from: http://cr.rosminzdrav.ru/recomend/155_1 (in Russ.)

17. Presidential Decree of Russian Federation “On national goals of development of Russian Federation during the period before 2030 year” dated 21.07.2020 №474 [cited 2021 May 12]. Available from: http://publication.pravo.gov.ru/Document/View/0001202007210012 (In Russ.)

18. Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Eng J Med. 2017;377(14):1319-30. DOI: 10.1056/NEJMoa1709118.

19. Steffel J, Eikelboom JW, Anand SS, et al. The COMPASS trial: net clinical benefit of low-dose rivaroxaban plus aspirin as compared with aspirin in patients with chronic vascular disease. Circulation. 2020;142(1):40-8. DOI:10.1161/CIRCULATIONAHA.120.046048.

20. Sharma M, Hart RG, Connolly SJ, et al. Stroke outcomes in the COMPASS trial. Circulation. 2019;(139):1134-45. DOI:10.1161/CIRCULATIONAHA.118.035864

21. Federal State Statistics Service. Data of statistical form N 12 in 2020. Moscow: TsNIIOIZ; 2021. (In Russ.)

22. Order of Ministry of Health of Russian Federation “On approval of standard of care for stable coronary artery disease (diagnostics, treatment and monitoring)” dated 28.04.2021 №410n [cited 2021 May 12]. Available from: http://publication.pravo.gov.ru/Document/View/0001202105240046 (in Russ.)

23. Federal State Statistics Service. Number of population in Russia in 2020 [cited 2021 May 12]. Available from: https://showdata.gks.ru/report/278928/ (In Russ.)

24. Zhuravleva MV, Zyryanov SK, Paleev FN, et al. Evaluation of the effect of the use of the drug ticagrelor in patients with acute coronary syndrome on achieving the target indicator “reduction of mortality from diseases of the circulatory system” in 2022-2024. Russian Journal of Cardiology. 2021;26(12):4819 (In Russ.) DOI:10.15829/1560-4071-2021-4819

25. Zhuravleva MV, Tereshchenko SN, Zhirov IV, et al. Effect of dapagliflozin in patients with heart failure on reducing cardiovascular mortality in federal project on the prevention of cardiovascular diseases. Russian Journal of Cardiology. 2020;25(10):4142 (In Russ.) DOI:10.15829/1560-4071-2020-4142.

26. Desperak P, Hudzik B, Gąsior M. Assessment of patients with coronary artery disease who may benefit from the use of rivaroxaban in the real world: implementation of the COMPASS trial criteria in the TERCET registry population. Pol Arch Intern Med. 2019;129(7-8):460-8. DOI:10.20452/pamw.14907.