Rational Pharmacotherapy in Cardiology

Advanced search

Risk Controlling of Gastrointestinal Bleeding in Comorbid Patients with Cardiovascular Diseases

Full Text:


The issues of prevention of thromboembolic complications (TE) in the management of patients with atrial fibrillation (AF) are of leading importance. Recently, non-vitamin K antagonist oral anticoagulants (NOACs), previously known as new oral anticoagulants are used in the treatment and prevention of TE in patients with AF. A lot of data has been accumulated, in which the NOACs indications have been revised. As a result, the updating has been done in the Recommendations of European Society of Cardiology (2016), the project of Russian Society of Cardiology Guidelines (2017), as well as in the new Recommendations of the European Heart Rhythm Association (2018). At the same time, the issues of prevention ща hemorrhagic complications, especially gastrointestinal bleeding, remain unresolved. Currently, there are no clinical guidelines on the use of NOACs from the standpoint of prevention of gastrointestinal bleeding, as well as definition of the risk of gastrointestinal bleeding in the treatment of NOACs. The authors analyze the recommended algorithms for the evaluation of the risk of gastrointestinal bleeding in NOACs using.

About the Authors

O. Yu. Chizhova
North-Western State Medical University named after I.I. Mechnikov
Russian Federation

Olga Yu. Chizhova – MD, PhD, Professor, Chair of Propedeutics of Internal Diseases, Gastroenterology and Dietology

Piskarevskij prosp. 47, Saint-Petersburg, 195067

L. N. Belousova
North-Western State Medical University named after I.I. Mechnikov
Russian Federation

Liya N. Belousova – MD, PhD, Associate Professor, Chair of Propedeutics of Internal Diseases, Gastroenterology and Dietology,

Piskarevskij prosp. 47, Saint-Petersburg, 195067

I. G. Bakulin
North-Western State Medical University named after I.I. Mechnikov
Russian Federation

Igor G. Bakulin – MD, PhD, Professor, Head of Chair of Propedeutics of Internal Diseases, Gastroenterology and Dietology 

Piskarevskij prosp. 47, Saint-Petersburg, 195067


1. Global Health Observatory (GHO) data. [cited 2018 Jul 20. Available from:

2. Strategy of prevention and control of non-infectious diseases and injuries in the Russian Federation. [cited 2018 Jul 20]. Available from: (In Russ.)

3. Chugh SS, Havmoeller R, Narayanan K, et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation. 2014;129:837-47. doi: 10.1161/CIRCULATIONAHA.113.005119.

4. Colilla S, Crow A, PetkunW, et al. Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. adult population. Am J Cardiol. 2013;112:1142-7. doi: 10.1016/j.amjcard.2013.05.063.

5. Andersson T, Magnuson A, Bryngelsson IL, et al. All‐cause mortality in 272,186 patients hospitalized with incident atrial fibrillation 1995‐2008: a Swedish nationwide long-term casecontrol study. Eur Heart J. 2013;34:1061-7. doi: 10.1093/eurheartj/ehs469.

6. Benjamin EJ, Wolf PA, D’Agostino RB, et al. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998;98:946-52. doi: 10.1161/01.CIR.98.10.946.

7. Dox KA. CardioPulse: Anticoagulants reduce risk of death in atrial fi brillation patients by 38%. Eur Heart J. 2016;37:860-7. doi: 10.1093/eurheartj/ehw012.

8. Lip GY, Nieuwlaat R, Pisters R, et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on atrial fibrillation. Chest. 2010;137:263-72. doi: 10.1378/chest.09-1584.

9. Hughes M, Lip GY. Stroke and thromboembolism in atrial fibrillation: a systematic review of stroke risk factors, risk stratification schema and cost effectiveness data. Thromb Haemost. 2008;99:295-304. doi: 10.1160/TH07-08-0508.

10. Kirchhof P, Benussi S, Kotecha D, et al.; Authors/Task Force Members. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS: The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC). Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Endorsed by the European Stroke Organisation (ESO). Eur Heart J. 2016;37:2893-962. doi:10.1093/eurheartj/ ehw210.

11. Shubik YuV. Peculiar features of prevention of thromboembolic events in atrial fibrillation in Russia. Journal of Arrhythmology. 2017;87:5-6. (In Russ.)

12. Diagnosis and treatment of atrial fibrillation, recommendations of the Russian Society of Cardiology, Russian Society of Arrhythmology and Association of Cardiovascular Surgeons of Russia. Russian Journal of Cardiology. 2014;4(102):1-100. (In Russ.).

13. Edupuganti S, Xie C, Wyrzykowski M, et al. Bleeding Complications in Patients Receiving Direct Oral Anticoagulant Therapy in the Post Clinical Trial General Practice. American Journal of Clinical and Experimental Medicine. 2017;5(3):64-8. doi: 10.11648/j.ajcem.20170503.12.

14. Desai J, Kolb JM, Weitz JI, et al. Gastrointestinal bleeding with the new oral anticoagulants--defining the issues and the management strategies. Thromb Haemost. 2013;110:205-12. doi:10.1160/ TH13-02-0150.

15. Cheung KS, Leung WK. Gastrointestinal bleeding in patients on novel oral anticoagulants: Risk, prevention and management World J Gastroenterol. 2017;23(11):1954-63. doi: 10.3748/wjg. v23.i11.1954.

16. Vaduganathan M, Bhatt D. Gastrointestinal Bleeding With Oral Anticoagulation: Understanding the Scope of the Problem. Clin Gastroenterol Hepatol. 2017;15(5):691-3. doi: 10.1016/j.cgh. 2016.12.033.

17. Lanas-Gimeno A, Lanas A. Risk of gastrointestinal bleeding during anticoagulant treatment. Expert Opin Drug Saf. 2017;16(6):673-85. doi: 10.1080/14740338.2017.1325870.

18. Gage BF, Yan Y, Milligan PE, et al. Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J. 2006;151(3):713-9. doi: 10.1016/j.ahj.2005.04.017.

19. Fang MC, Go AS, Chang Y, et al. A new risk scheme to predict warfarin-associated hemorrhage: The ATRIA (Antic-oagulation and Risk Factors in Atrial Fibrillation) Study. J Am Coll Cardiol. 2011;58:395-401. doi: 10.1016/j.jacc.2011.03.031.

20. Pisters R, Lane DA, Nieuwlaat R, et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093-100. doi: 10.1378/chest.10-0134.

21. Omran H, Bauersachs R, Rubenacker S, et al. The HAS-BLED score predicts bleedings during bridging of chronic oral anticoagulaion. Results from the national multicentre BNK Online bRiDging REgistRy (BORDER). Thromb Haemost. 2012;108:65-73. doi: 10.1378/chest.10-0134.

22. Connolly SJ, Ezekowitz MD, Yusuf S, et al. RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-51. doi: 10.1056/NEJMoa0905561.

23. Patel MR, Mahaffey KW, Garg J, et al.; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883-91. doi: 10.1056/NEJMoa1009638.

24. Loukianov MM, Boytsov SA, Yakushin SS, et al. Diagnostics, treatment, associated cardiovascular and concomitant non-cardiac diseases in patients with diagnosis of “atrial fibrillation” in real outpatient practice (according to data of REgistry of CardioVAScular diseAses, RECVASA). Rational Pharmacotherapy in Cardiology. 2014;10(4):366-77. (In Russ).

25. Erlikh AD, Gratsiansky NA; on behalf of participants RECORD-3 REGISTERS Registry of Acute Coronary Syndromes “RECORD-3”. Characteristics of Patients and Treatment Until Discharge During Initial Hospitalization. Kardiologiia. 2016;56(4):16-24. (In Russ.)

26. Tereshchenko SN, Zhirov IV, Osmolovskaya YuF, et al. The Russian register of patients with chronic heart failure and atrial fibrillation (RIF-CHF): clinical and demographic characteristics of the sample at the time of inclusion in the register. ZHurnal Serdechnaya Nedostatochnost'. 2016;17(6):418-(In Russ)

27. Serdecnaya EV, Yurieva SV, Ryabaya IN. Prevention of stroke in a patient with atrial fibrillation in the practice of a physician-therapist. Public health: traditions, innovations, perspectives: Trudnyy Patsiyent. 2016;4-5:143-4. (In Russ.)

28. Granger CB, Alexander JH, McMurray JJ, et al., for the ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981‐92. doi: 10.1056/NEJMoa1107039.

29. Nessel C, Mahaffey K, Piccini J, et al. Incidence and Outcomes of Gastrointestinal Hemorrhage in Patients With Atrial Fibrillation Treated With Rivaroxaban or Warfarin: Results From the ROCKET AF Trial. Chest. 2012;142(4) Suppl:84A. doi: 10.1378/chest.1388403.

30. Cannon CP, Kohli P. Danger ahead: watch out for indirect comparisons! J Am Coll Cardiol. 2012;60:747-8.

31. McMurray JJ, Ezekowitz JA, Lewis BS, et al. Left ventricular systolic dysfunction, heart failure, and the risk of stroke and systemic embolism in patients with atrial fibrillation: insights from the ARISTOTLE trial. Circ Heart Fail. 2013;6(3):451-60. doi: 10.1161/CIRCHEARTFAILURE.112.000143.

32. Kirchhof P, Radaideh G, Kim YH, et al. Safety analysis of rivaroxaban: a pooled analysis of the global XANTUS programme (real-world, prospective, observational studies for stroke prevention in patients with atrial fibrillation). Poster 86691 presented at the 2017 European Society of Cardiology (ESC) Congress, 26-30 August 2017; Barcelona, Spain.

33. Hecker J, Marten S, Keller L, et al. Effectiveness and safety of rivaroxaban therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOAC Registry. Thromb Haemost. 2016;115:939949. doi: 10.1160/TH15-10-0840.

34. Beyer-Westendorf J, Ebertz F, Gelbricht V, et al. Real life efficacy and safety of rivaroxaban for stroke prevention in atrial fibrillation: updated results of the prospective NOAC registry (NCT01588119). Eur Heart J. 2013;34(1):P4870. doi: 10.1093/eurheartj/eht310.p4870.

35. Tamayo S, Frank Peacock W, Patel M, et al. Characterizing major bleeding in patients with nonvalvular atrial fibrillation: a pharmacovigilance study of 27 467 patients taking rivaroxaban. Clin Cardiol. 2015;38:63-8.

36. Pokorney SD. Patients’ time in therapeutic range on warfarin among US patients with atrial fibrillation: Results from ORBIT-AF registry. Am Heart J. 2015;170:141-8.e1. doi: 10.1016/j.ahj.2015.03.017.

37. Renda G, De Caterina R. The new oral anticoagulants in atrial fibrillation: once daily or twice daily? Vascul Pharmacol. 2013;59:53—62. doi: 10.1016/j.vph.2013.07.003.

38. Arutyunov GP. Place and importance of observational studies of PLA in patients with non-valvular atrial fibrillation from the perspective of evidence-based medicine. Serdtse. 2016;15(6):441-7. (In Russ.).

39. Martsevich SYu, Lukina YV, Kutishenko NP. Once again about the Hierarchy of Evidences in Medicine or whether it is Possible to Choose the Most Effective and Safe Drug with the Help of Observational Studies. Rational Pharmacotherapy in Cardiology. 2017;13(2):270-4. (In Russ.).

40. Xu W, Hu S, Wu T. Risk analysis of new oral anticoagulants for gastrointestinal bleeding and intracranial hemorrhage in atrial fibrillation patients: a systematic review and network meta-analysis. J Zhejiang Univ Sci B. 2017;18:567-76. doi: 10.1631/jzus.B1600143.

41. Chai-Adisaksopha C, Crowther M, Isayama T, et al. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood. 2014;124:2450-8. doi: 10.1182/blood-2014-07-590323.

42. Masharova AA. Anticoagulation Therapy: Gastroenterologists' Opinion. Doctor.Ru. 2015;8 (109)9(110):9-13. (In Russ.) [Машарова А. А. Антикоагулянтная терапия: точка зрения гастроэнтеролога. Доктор.Ру. Терапия Кардиология Ревматология. 2015;8 (109)-9(110):9-13.

43. Manatsathit W, Al-Hamid H, Leelasinjaroen P, et al. Management of gastrointestinal bleeding in patients anticoagulated with dabigatran compared with warfarin: a retrospective, comparative case review. Cardiovascular Diagnosis and Therapy. 2014;4:224-31. doi: 10.3978/j.issn.2223-3652. 2014.03.07.

44. Heidbuchel H, Verhamme P, Alings M, et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2015;17(10):1467-507. doi: 10.1093/europace/euv309.

45. Heidbuchel H, Verhamme P, Alings M, et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013;15:625-51. doi: 10.1093/europace/eut083.

46. Chang HY, Zhou M, Tang W, et al. Risk of gastrointestinal bleeding associated with oral anticoagulants: population based retrospective cohort study. BMJ. 2015;350:h1585. bmj.h1585.

47. Abraham NS, Singh S, Alexander GC, et al. Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study. BMJ. 2015;350:h1857.

48. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64:2246-80. doi: 10.1016/j.jacc.2014.03.021.

49. Instructions for the use of the drug Xarelto® 15/20 mg (version dated 12.02.2018). [cited 2018 Jul 20. Available from: (In Russ.)

50. Instructions for the use of the drug Eliquis® 15/20 mg (version dated 12.02.2018). [cited 2018 Jul 20. Available from: (In Russ.)

51. Instructions for the use of the drug Pradaxa® 15/20 mg (version dated 12.02.2018). [cited 2018 Jul 20. Available from: (In Russ.)

52. Radaelli F, Dentali F, Repici A, et al. Management of anticoagulation in patients with acute gastrointestinal bleeding. Digestive and Liver Disease. 2015;47:621-7. doi: 10.1016/j.dld.2015.03.029.

53. Vasilyev S, Smirnova E, Popov D, et al. A New-Generation Fecal Immunochemical Test (FIT) Is Superior to Quaiac-based Test in Detecting Colorectal Neoplasia Among Colonoscopy Referral Patients. Anticancer Research. 2015;35(5):2873-80.

For citation:

Chizhova O.Yu., Belousova L.N., Bakulin I.G. Risk Controlling of Gastrointestinal Bleeding in Comorbid Patients with Cardiovascular Diseases. Rational Pharmacotherapy in Cardiology. 2018;14(4):583-590. (In Russ.)

Views: 355

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

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