WARFARIN AND ITS IMPORTANCE IN THE ERA OF NEW ORAL ANTICOAGULANTS. ISSUES OF MONITORING THE EFFECTIVENESS AND SAFETY OF TREATMENT

Oral anticoagulant (OAC) therapy is currently gaining special importance due to the significant spread of atrial fibrillation (AF) in the population (especially in older age groups). The use of OAC in AF has an extensive evidence base, which confirms a significant decrease in the number of strokes and total mortality in the context of anticoagulation therapy (ACT) in AF. Currently, the "gold standard" of the OAC is warfarin, which has proved effectiveness in all categories of patients with AF. A whole group  of new OAC (NOAC) also appeared. In Russia, dabigatran, rivaroxaban and apixaban have been registered. All NOAC were studied in randomized clinical trials (RCTs) in comparison with warfarin, mainly in patients with non-valvular AF, therefore, in valvular AF, as well as in patients with severe renal failure, warfarin remains the drug of choice. Advantages of warfarin in comparison with NOAC are the presence of known  antidote and standardized indicator of the efficacy and safety of the anticoagulation therapy – International Normalized Ratio (INR), as well as low price of the drug. The leading problem in the treatment of warfarin is the complexity and, at the same time, a strong  need to maintain INR within the therapeutic "window" of at least 60% of the treatment time. Obviously, the optimal solution to this problem is the possibility of self-testing of this indicator by the patient himself and,  probably, the ability to adjust the dosage of warfarin independently, to achieve the necessary values of INR (self-management) or titrate the dose with the help of a medical consultation by phone (self-monitoring). To date, several devices have been developed for self-monitoring of anticoagulation therapy – coagulometers. Their use leads to a decrease in the number of thromboembolic complications, and from the results of some RCTs – to a decrease in the number of large bleedings and total mortality, and to improve the quality of life of AF patients who  need  constant anticoagulation therapy. The high economic efficiency of using coagulometers has  also been  confirmed. Coagulometer CoaguChek  (Roche, Switzerland) has the largest evidence base for self-monitoring of INR and its impact on the efficacy and safety of anticoagulation therapy.

1. Zoni-Berisso M, Lercari F, Carazza T, Domenicucci S. Epidemiology of atrial fibrillation: European perspective. Clin Epidemiol. 2014; 6: 213-20. doi: 10.2147/CLEP.S47385.

2. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146:857-67

3. Fauchier L, Philippart R, Clementy N et al. How to define valvular atrial fibrillation? Arch Cardiovasc Dis. 2015;108(10):530-9. doi: 10.1016/j.acvd.2015.06.002.

4. Di Pasquale G, Zagnoni S, Riva L. Novel oral anticoagulants and valvular atrial fibrillation: are they always contraindicated? Intern Emerg Med. 2015 Feb;10(1):21-4. doi: 10.1007/s11739-014-1181-5.

5. Eikelboom JW, Connoly SJ, Brueckmann M et al. for the REALIGN Investigators. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369:1206-14. doi: 10.1111/jth.12500.

6. White HD, Gruber M, Feyzi J et al. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Intern Med. 2007;167(3):239-45. doi: 10.1001/archinte.167.3.239

7. Gómez-Outes A., Terleira-FernЗndez AI, Calvo-Rojas G. et al. Dabigatran, Rivaroxaban, or Apixaban versus Warfarin in Patients with Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis of Subgroups. Thrombosis. 2013;2013:640723. doi: 10.1155/2013/640723

8. Garcia-Alamino JM, Ward AM, Alonso-Coello P. et al. Self-monitoring and self-management of oral anticoagulation. Cochrane Database Syst Rev. 2010;4(4):CD003839. : doi: 10.1002/14651858. CD003839.pub2

9. Sharma P, Scotland G, Cruickshank M. et al. The clinical effectiveness and cost-effectiveness of pointof-care tests (CoaguChek system, INRatio2 PT/INR monitor and ProTime Microcoagulation system) for the self-monitoring of the coagulation status of people receiving long-term vitamin K antagonist therapy, compared with standard UK practice: systematic review and economic evaluation. Health Technol Assess. 2015;19(48):1-172. doi: 10.3310/hta19480

10. Heneghan CJ, Garcia-Alamino JM, Spencer EA. Self-monitoring and self-management of oral anticoagulation. Cochrane Database Syst Rev. 2016;7:CD003839. doi: 10.1002/14651858.CD003839.pub3.

11. Heneghan C, Ward A, Perera R. et al. Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data. Lancet. 2012;379(9813):322-34. doi: 10.1016/S0140-6736(11)61294-4.

12. Martsevich S.Y., Navasardyan A.R., Kutishenko N.P. et al. The assessment of compliance to the use of new oral anticoagulants in patients with atrial fibrillation according to the PROFILE register. Rational Pharmacotherapy in Cardiology. 2014;10(6):625-30. (In Russ.) [Марцевич С.Ю., Навасардян А.Р., Кутишенко Н.П. и соавт. Оценка приверженности к приему новых пероральных антикоагулянтов у пациентов с фибрилляцией предсердий по данным регистра ПРОФИЛЬ. Рациональная Фармакотерапия в Кардиологии. 2014;10(6):625-30]. DOI:10.20996/1819-6446-2014-10-6-625-630

13. Craig JA, Chaplin S, Jenks M. Warfarin monitoring economic evaluation of point of care self-monitoring compared to clinic settings. J Med Econ. 2014;17(3):184-90. doi: 10.3111/13696998.2013.877468