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Features of Modern Anticoagulant Therapy in Patients with Nonvalvular Atrial Fibrillation and Chronic Kidney Disease

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Prevalence of atrial fibrillation (AF) in population is very high and continues to grow. According to the existing statistics its prevalence reaches about 2% so it is twice more, than it was considered in the last decade. Prevalence of AF among patients with chronic kidney disease (CKD) varies from 11 to 22% (according to other data – from 15 to 20%) and increases with age, considerably surpassing that in the general population among all age groups. Vast majority of patients with AF need in treatment with anticoagulants to prevent an ischemic stroke and systemic thromboembolisms. However, in case of combination AF and CKD, in addition to increase in frequency of strokes and the thromboembolic events, also the frequency of major bleedings significantly increases that considerably complicates the choice of adequate anticoagulant therapy in such situation. Many years the vitamin K antagonists were the only representatives of a class of anticoagulants for long-term therapy in patients with AF. Their well-known deficiencies (a narrow therapeutic window, need of frequent laboratory control, numerous drug-drug and dietary interactions, unpredictability of a pharmacodynamics and pharmacokinetics at certain patients) promoted search of new medicines, more convenient in use. Direct oral anticoagulants were easier to use, and by results of the main studies didn't yield or exceeded warfarin concerning balance of efficiency and safety. However, they were not specially studied in patients with the reduced kidney function. Features of modern anticoagulant therapy in patients with the nonvalvular AF and CKD are considered in the review. The possibility of the safest use of anticoagulants for patients with decreased creatinine clearance is analyzed.

About the Authors

I. S. Daabul
I.M. Sechenov First Moscow State Medical University. Trubetskaya ul. 8-2, Moscow, 119991 Russia
Russian Federation

MD, PhD Student of Chair of Faculty Therapy #1, I.M. Sechenov First Moscow State Medical University

A. A. Sokolova
I.M. Sechenov First Moscow State Medical University. Trubetskaya ul. 8-2, Moscow, 119991 Russia
Russian Federation

MD, PhD, Deputy Director for Educational Activities, Institute of Personalized Medicine, I.M. Sechenov First Moscow State Medical University

D. A. Napalkov
I.M. Sechenov First Moscow State Medical University. Trubetskaya ul. 8-2, Moscow, 119991 Russia
Russian Federation

MD, PhD, Professor of Chair of Faculty Therapy #1, I.M. Sechenov First Moscow State Medical University


1. Zoni-Berisso M., Lercari F., Carazza T., et al. Epidemiology of atrial fibrillation: European perspective. Clin Epidemiol 2014; 6: 213-20.

2. National guidelines on the diagnosis and treatment of atrial fibrillation (2012). Available at: Retrieved 09/18/2016. In Russian (Национальные рекомендации по диагностике и лечению фибрилляции предсердий (2012). Доступно на:Проверено 18.09.2016).

3. Smirnov AV, Shilov EM, Dobronravov VA National guidelines. Chronic kidney disease: the basic principles of screening, diagnosis, prevention and treatment approaches. St. Petersburg: Levsha; 2012. In Russian (Смирнов А. В., Шилов Е. М., Добронравов В. А. Национальные рекомендации. Хроническая болезнь почек: основные принципы скрининга, диагностики, профилактики и подходы к лечению. СПб.: Левша: 2012).

4. Schwartzenberg, S., Lev EI., Sagie A., et al. The Quandary of Oral Anticoagulation in Patients With Atrial Fibrillation and Chronic Kidney Disease. Am J Cardiol 2016; 117(3): 477- 82.

5. Alonso A., Lopez FL., Matsushita K., et al. Chronic kidney disease is associated with the incidence of atrial fibrillation: the Atherosclerosis Risk in Communities (ARIC) study. Circulation 2011; 123(25): 2946-53.

6. Wheeler D.S., Giugliano R.P., Rangaswami J. Anticoagulation-related nephropathy. Thromb Haemost 2016; 14(3): 461-67.

7. Sardar P. Chatterjee S., Herzog E., et al. Novel oral anticoagulants in patients with renal insufficiency: a meta-analysis of randomized trials. Can J Cardiol 2014; 30(8): 888-97.

8. Schurgers L.J., Aebert H., Vermeer C., et al. Oral anticoagulant treatment: friend or foe in cardiovascular disease? Blood 2004; 104(10): 3231-2.

9. Pankratov V., Pigarova EA, Dzeranova L. K. Vitamin K-dependent proteins: osteocalcin, the Gla-protein matrix and vnekostnye effects. Ozhirenie i Metabolizm 2013; (2): 11-8. In Russian (Панкратова Ю. В., Пигарова Е. А., Дзеранова Л. К. Витамин К-зависимые белки: остеокальцин, матриксный Gla-белок и их внекостные эффекты. Ожирение и метаболизм 2013; (2): 11 - 8).

10. Luo G., Ducy P., McKee MD., et al. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 1997; 386(6620): 78-81.

11. Price P.A., Faus S.A., Williamson M.K. Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves. Arterioscler Thromb Vasc Biol 1998; 18(9): 1400-7.

12. Koos R., Mahnken AH., Mühlenbruch G., et al. Relation of oral anticoagulation to cardiac valvular and coronary calcium assessed by multislice spiral computed tomography. Am J Cardiol 2005; 96(6): 747-9.

13. Weijs B., Blaauw Y., Rennenberg RJ., et al. Patients using vitamin K antagonists show increased levels of coronary calcification: an observational study in low-risk atrial fibrillation patients. Eur Heart J 2011; 32(20): 2555-62.

14. Chatrou M.L., Winckers K., Hackeng TM., et al. Vascular calcification: the price to pay for anticoagulation therapy with vitamin K-antagonists. Blood Rev 2012; 26(4): 155-66.

15. Braam L.A., Hoeks AP., Brouns F., et al. Beneficial effects of vitamins D and K on the elastic properties of the vessel wall in postmenopausal women: a follow-up study. Thromb Haemost 2004; 91(2): 373-80.

16. Connolly S.J., Ezekowitz MD., Yusuf S., et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361(12): 1139-51.

17. Patel M.R., Mahaffey KW., Garg J., et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365(10): 883-91.

18. Granger C.B., Alexander JH., McMurray JJ., et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365(11): 981-92.

19. Heidbuchel H., Verhamme P., Alings M., et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015; 17(10): 1467-507.

20. Hijazi Z., Hohnloser SH., Oldgren J., et al. Efficacy and safety of dabigatran compared with warfarin in relation to baseline renal function in patients with atrial fibrillation: a RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) trial analysis. Circulation 2014; 129(9): 961-70.

21. Böhm M., Ezekowitz MD., Connolly SJ., et al. Changes in Renal Function in Patients With Atrial Fibrillation: An Analysis From the RE-LY Trial. J Am Coll Cardiol 2015; 65(23): 2481-93.

22. Sparkenbaugh E.M., Chantrathammachart P., Mickelson J., et al. Differential contribution of FXa and thrombin to vascular inflammation in a mouse model of sickle cell disease. Blood 2014; 123(11): 1747-56.

23. Lee I.O., Kratz MT., Schirmer SH., et al. The effects of direct thrombin inhibition with dabigatran on plaque formation and endothelial function in apolipoprotein E-deficient mice. J Pharmacol Exp Ther 2012; 343(2): 253-7.

24. Preusch M.R., Ieronimakis N., Wijelath ES., et al. Dabigatran etexilate retards the initiation and progression of atherosclerotic lesions and inhibits the expression of oncostatin M in apolipoprotein E-deficient mice. Drug Des Devel Ther 2015; 9: 5203-11.

25. Hara T., Fukuda D., Tanaka K., et al. Rivaroxaban, a novel oral anticoagulant, attenuates atherosclerotic plaque progression and destabilization in ApoE-deficient mice. Atherosclerosis 2015; 242(2): 639-46.

26. Landray M.J., Wheeler DC., Lip GY., et al. Inflammation, endothelial dysfunction, and platelet activation in patients with chronic kidney disease: the chronic renal impairment in Birmingham (CRIB) study. Am J Kidney Dis 2004; 43(2): 244-53.

27. Brodsky S.V., Nadasdy T., Rovin BH., et al. Warfarin-related nephropathy occurs in patients with and without chronic kidney disease and is associated with an increased mortality rate. Kidney Int 2011; 80(2): 181-9.

28. Brodsky S.V., Collins M., Park E., et al. Warfarin therapy that results in an International Normalization Ratio above the therapeutic range is associated with accelerated progression of chronic kidney disease. Nephron Clin Pract 2010; 115(2): 142-6.

29. Fox K.A., Piccini JP., Wojdyla D., et al. Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment. Eur Heart J, 2011; 32(19): 2387-94.

30. Eto M., Barandiér C., Rathgeb L., et al. Thrombin suppresses endothelial nitric oxide synthase and upregulates endothelin-converting enzyme-1 expression by distinct pathways: role of Rho/ROCK and mitogen-activated protein kinase. Circ Res 2001; 89(7): 583-90.

31. Zhou, Q., Bea F., Preuschet M., al. Evaluation of plaque stability of advanced atherosclerotic lesions in apo E-deficient mice after treatment with the oral factor Xa inhibitor rivaroxaban. Mediators Inflamm 2011; 2011: 432080.

32. Mega J.L., Braunwald E., Wiviott SD., et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2012; 366(1): 9-19.

33. Hohnloser S.H., Hijazi Z., Thomas L., et al. Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J 2012; 33(22): 2821-30.

34. Esmon C.T. Targeting factor Xa and thrombin: impact on coagulation and beyond. Thromb Haemost 2014; 111(4): 625-33.

For citation:

Daabul I.S., Sokolova A.A., Napalkov D.A. Features of Modern Anticoagulant Therapy in Patients with Nonvalvular Atrial Fibrillation and Chronic Kidney Disease. Rational Pharmacotherapy in Cardiology. 2016;12(5):595-602. (In Russ.)

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