Rational Pharmacotherapy in Cardiology

Advanced search


Full Text:


Studies data on new anticoagulants, direct oral thrombin inhibitor (dabigatran) and direct inhibitors of coagulation factor Xa (rivaroxaban, apixaban), in the treatment of nonvalvular atrial fibrillation are presented. Effects of these drugs on cardiovascular events in atrial fibrillation are analyzed based on the results of various studies. Prospects for further research are discussed.

About the Authors

Z. M. Safiullina
Tyumen State Medical Academy
Russian Federation

S. V. Shalaev
Tyumen State Medical Academy; Cardiology Clinic, Tyumen Regional Clinical Hospital №1
Russian Federation


1. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991;22:983–.

2. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation: a major contributor to stroke in the elderly: the Framingham Study. Arch Intern Med 1987;147: 1561–.

3. Connolly SJ, Ezekowitz MD, Yusuf S, et al.; RE-LY Steering Committee and Investigators. Dabigatran vs. warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139–151.

4. Gage BF. Can We Rely on RE-LY? N Engl J Med 2009; 361:1201–202.

5. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Newly identified events in the RE-LY trial. N Engl J Med 2010;363:1875–876.

6. Oldgren J, Alings M, Darius H, et al; RE-LY Investigators. Risks for stroke, bleeding, and death in patients with atrial fibrillation receiving dabigatran or warfarin in relation to the CHADS2 score: a subgroup analysis of the RE-LY trial. Ann Intern Med 2011;155:660–67.

7. Hohnloser SH, Oldgren J, Yang S, et al. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Circulation 2012;125:669–76.

8. Uchino K, Hernandez AV. Dabigatran association with higher risk of acute coronary events: meta-analysis of noninferiority randomized controlled trials. Arch Intern Med 2012;172:397–02.

9. Lip GY, Lane DA. Does warfarin for stroke thromboprophylaxis protect against MI in atrial fibrillation patients? Am J Med 2010;123:785–89.

10. Mak KH. Coronary and mortality risk of novel oral antithrombotic agents: a meta-analysis of large randomized trials. BMJ Open 2012;2(5). pii: e001592.

11. Sarich TC, Wolzt M, Eriksson UG, et al. Effects of ximelagatran, an oral direct thrombin inhibitor, rhirudin and enoxaparin on thrombin generation and platelet activation in healthy male subjects. Jam Coll Cardiol 2003;41:557–4.

12. Bostrom SL, Hansson GF, Kiaer M, et al. Effects of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran, and dalteparin on the endogenous thrombin potential in venous blood from healthy male subjects. Blood Coagul Fibrinolysis 2003;14:457–2.

13. Green L, Lawrie AS, Patel S, et al. The impact of elective knee/hip replacement surgery and thromboprophylaxis with rivaroxaban or dalteparin on thrombin generation. Br J Haematol 2010;15:469– 76.

14. Perzbon R, Harwardt M, Heitmeier S, et al. The effect of the oral direct factor Xa inhibitor rivaroxaban on tissue factor mediated in vitro platelet aggregation is enhanced by a P2Y receptor block (abstract). J Thromb Haemost 2011;9:74.

15. Furugohri T, Sugiyama N, Morishima Y, et al. Antithrombin-independent thrombin inhibitors, but not direct Xa inhibitors, enhance thrombin generation in plasma through inhibition of thrombin-thrombomodulin-protein C system. Thromb Haemost 2011;106:1076–3.

16. Christersson C, Oldgren J, Wallentin L, et al. Treatment with an oral direct thrombin inhibitor decreases platelet activity but increases markers of inflammation in patients with myocardial infarction. J Intern Med 2011;270:215–3.

17. Ezekowitz MD, Reilly PA, Nehmiz G, et al. Dabigatran with and without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study). Am J Cardiol 2007;100:1419–6.

18. Eikelboom J, Oldgren J, Reilly P, et al. No evidence of platelet activation in patients with atrial fibrillation who are treated with dabigatran: a substudy of the RELY Trial (abstract). J Thromb Haemost 2011;9:346.

19. Patel MR, Mahaffey KW, Garg J, et al.; ROCKET AF Investigators. Rivaroxaban vs. warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883–91.

20. FDA Draft Briefing Document for the Cardiovascular and Renal Drugs Advisory Committee (CRDAC). Available at: drugs/CardiovascularandRenalDrugsAdvisoryCommittee/ucm270796.pdf. Date of access 18/04/2013.

21. Connolly SJ, Eikelboom J, Joyner C, et al; AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med 2011;364:806–17.

22. Granger CB, Alexander JH, McMurray JJ, et al.; ARISTOTLE Committees and Investigators. Apixaban vs. warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981–92.

23. Hohnloser SH, 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 J2012;33:2821–830.

24. Banerjee A, Lane DA, Torp-Pedersen C, Lip GY. Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) vs. no treatment in a ‘real world’ atrial fibrillation population: a modelling analysis based on a nationwide cohort study. Thromb Haemost 2012;107:584–89.

25. Mega JL, Braunwald E, Wiviott SD, et al.; ATLAS ACS 2–IMI 51 Investigators. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2012;366:9–9.

26. Alexander JH, Lopes RD, James S, et al.; APPRAISE-2 Investigators. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med 2011;365:699–08.

27. Price J, Hynes M, Labinaz M et al. Mechanical valve thrombosis with dabigatran. J Am Coll Cardiol 2012;60(17):1710–.

28. Boehringer Ingelheim discontinues Phase II trial in patients with artificial heart valves. Press release. Available at: Date of access 18/04/2013.

29. FDA Drug Safety Communication: Pradaxa (dabigatran etexilate mesylate) should not be used in patients with mechanical prosthetic heart valves. Available at: Date of access 18/04/2013.

30. Opinions on safety variations. Adopted at the CHMP meeting of 10–3 December 2012. Available at: Date of access 18/04/2013.

31. Komocsi A., Vorobcsuk A., Kehl D., Aradi D. Use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an acute coronary syndrome. Arch Intern Med 2012; DOI:10.1001/archinternmed.2012.4026.

32. Hernandez AV. No place for novel oral anticoagulants in current treatment of acute coronary syndromes. Arch Intern Med 2012;172(20):1546–.

33. Nainggolan L. No place for new anticoagulants in ACS, says new review. Available at: Date of access 18/04/2013.

34. Ruff C.T., Giugliano R.P., Antman E.M., et al. Evaluation of the novel factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation: design and rationale for the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation-Thrombolysis In Myocardial Infarction study 48 (ENGAGE AF-TIMI 48). Am Heart J 2010;160:635–1.


For citation:

Safiullina Z.M., Shalaev S.V. ERA OF NEW ANTICOAGULANTS IN THE TREATMENT OF NON-VALVULAR ATRIAL FIBRILLATION: PROSPECTS AND CHALLENGES. Rational Pharmacotherapy in Cardiology. 2013;9(2):171-176. (In Russ.)

Views: 523

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)