Comparison of the Endoscopic Picture in Case of Complications of the upper Gastrointestinal Tract Caused by the Use of Antithrombotic Agents and Non-Steroidal Anti-Inflammatory Drugs

Intaking antithrombotic funds (ATA) and non-steroidal anti-inflammatory drugs (NSAIDs) is one of the most frequent causes of pathology in gastrointestinal (GI) tract.
The purpose of the study: comparison of pathological changes of the mucous membrane in the upper GI tract, that occur against the background of ATA and NSAIDs admission.
Material and methods. Endoscopic data of two groups of patients taking ATA and NSAIDS have been compared. The first group of 448 patients from the 10th Gastrointestinal Department in N.N. Burdenko Main Military Clinical Hospital was on record from 2013 to 2017. The patients had erosive ulcerous changes of gastrointestinal mucosa, occurred against the background of the ATA admission. The second group comprised 6431 patients with rheumatic diseases. They were hospitalized in the clinic of V.A. Nasonova Research Institute of Rheumatology in the period from 2007 to 2016 and took NSAIDs regularly.
Results. Duodenal and gastric ulcer changes in gastric mucosa and duodenal ulcers were identified in 168 (37.5 %) patients taking ATA and in 1691 (26.3 %) patient treated with NSAIDS. Structure of pathology varied. So, against the background of ATA and NSAIDS admission, the number of acute gastric ulceration amounted to 6.5 % and 15.5 % (p < 0.001); acute ulcers duodenal was 2.9 % and 4.9 %; combined ulcerative lesions of gastric and duodenal was 2.9 % and 2.0 %; multiple erosions of gastroduodenal mucosa were 52.4 % and 15.7 % (p < 0.001); single erosion was 35. 1% and 61.6 %. The factor of ulcer history and age ≥ 65 years old increased significantly the risk of duodenal and gastric ulcer changes in patients taking ATA and NSAIDs: OR 5.182 (95% CI 2.701–9.942) and 3.24 (95% CI 2.19–5.34), 4.537 (95% CI 2.036–10.11) and 2.016 (95% CI 1.230–2.917) respectively. Intaking of proton pump inhibitor (PPI) reduced significantly the risk of complications for both ATA and NSAIDs: OR 0.329 (95% CI 0.199–0.546) and 0.317 (95% CI 0.210–0.428) respectively.
Conclusion. The structure of pathology of mucous in the upper gastrointestinal tract that arose against the backdrop of ATA and NSAIDs admission is different. The first is characterized by a multiple erosion, while the second one has single acute distal gastric ulcers. The ulcerative history and advanced age of patients increase significantly the risk of complications concerning the gastroduodenal mucosa when using ATA and NSAIDs. PPI is the effective means of preventing this pathology.

1. Raskin JB, White RH, Jackson JE, Weaver AL, Tindall EA, Lies RB, et al. Misoprostol dosage in the prevention of nonsteroidal anti-inflammatory drug-induced gastric and duodenal ulcers: a comparison of three regimens. Ann Intern Med. 1995; 123(5): 344-350. doi: 10.7326/0003-4819-123-5-199509010-00004

2. Moroz EV, Karateev AE, Kryukov EV, Chernetsov VA. Gastrointestinal bleeding when using the new oral anticoagulants: epidemiology, risk factors, prevention and treatment. Nauchno-prakticheskaya revmatologiya. 2017; 55(6): 675-684. doi: 10.14412/1995-4484-2017-675-684. (In Russ.)

3. Cullen D, Bardhan KD, Eisner M, Kogut DG, Peacock RA, Thomson JM, et al. Primary gastroduodenal prophylaxis with omeprazole for non-steroidal anti-inflammatory drug users. Aliment Pharmacol Ther. 1998; 12(2): 135-140. doi: 10.1046/j.1365-2036.1998.00288.x

4. Gralnek IM, Dumonceau JM, Kuipers EJ, Lanas A, Sanders DS, Kurien M, et al. Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2015; 47(10): a1-46. doi: 10.1055/s-0034-1393172.

5. Ekström P, Carling L, Wetterhus S, Wingren PE, Anker-Hansen O, Lundegårdh G, et al. Prevention of peptic ulcer and dyspeptic symptoms with omeprazole in patients receiving continuous non-steroidal anti-inflammatory drug therapy. A Nordic multicentre study. Scand J Gastroenterol 1996; 31(8): 753-758. doi: 10.3109/00365529609010347

6. Laursen SB. Treatment and prognosis in peptic ulcer bleeding. Dan Med J. 2014; 61(1): B4797.

7. Graham DY, Agrawal NM, Campbell DR, Haber MM, Collis C, Lukasik NL, et al. Ulcer prevention in long-term users of nonsteroidal anti-inflammatory drugs. Arch Intern Med. 2002; 162(2): 169-175. doi: 10.1001/archinte.162.2.169

8. Federal State Statistics Service. Healthcare in Russia 2017. Moscow; 2017. (In Russ.)

9. Hunt RH, Harper S, Callegari P, Yu C, Quan H, Evans J, et al. Complementary studies of the gastrointestinal safety of the cyclo-oxygenase-2-selective inhibitor etoricoxib. Aliment Pharmacol Ther. 2003; 17(2): 201-210. doi: 10.1046/j.1365-2036.2003.01407.x

10. Karateev AE, Nasonov EL, Ivashkin VT, Martynov AI, Yakhno NN, Arutyunov GP, et al. Rational use of nonsteroidal anti-inflammatory drugs. Clinical guidelines. Rheumatology Science and Practice. 2018; 56: 1-29. doi: 10.14412/1995-4484-2018-1-29. (In Russ.)

11. Hunt RH, Harper S, Watson DJ, Yu C, Quan H, Lee M, et al. The gastrointestinal safety of the COX-2 selective inhibitor etoricoxib assessed by both endoscopy and analysis of upper gastrointestinal events. Am J Gastroenterol. 2003; 98(8): 1725-1733. doi: 10.1111/j.1572-0241.2003.07598.x

12. Fashner J, Gitu AC. Diagnosis and treatment of peptic ulcer disease and H. pylori infection. Am Fam Physician. 2015; 91(4): 236-242.

13. Karateev AE, Nasonov VA. Development and relapse of gastroduodenal ulcer in patients taking nonsteroid anti-inflammatory drugs: effects of standard risk factors. Terapevticheskiy arkhiv. 2008; 80(5): 62-66. (In Russ.)

14. Deutsch D, Boustière C, Ferrari E, Albaladejo P, Morange PE, Benamouzig R. Direct oral anticoagulants and digestive bleeding: therapeutic management and preventive measures. Therap Adv Gastroenterol. 2017; 10(6): 495-505. doi: 10.1177/1756283X17702092

15. Cheung KS, Leung WK. Gastrointestinal bleeding in patients on novel oral anticoagulants: Risk, prevention and management. World J Gastroenterol. 2017; 23(11): 1954-1963. doi: 10.3748/wjg.v23.i11.1954

16. Lavie CJ, Howden CW, Scheiman J, Tursi J. Upper gastrointestinal toxicity associated with long-term aspirin therapy: consequences and prevention. Curr Probl Cardiol. 2017; 42(5): 146-164. doi: 10.1016/j.cpcardiol.2017.01.006

17. Cryer B, Mahaffey KW. Gastrointestinal ulcers, role of aspirin, and clinical outcomes: pathobiology, diagnosis, and treatment. J Multidiscip Healthc. 2014; 7: 137-146. doi: 10.2147/JMDH.S54324

18. Lanas A, Chan FKL. Peptic ulcer disease. Lancet. 2017; 390(10094): 613-624. doi: 10.1016/S0140-6736(16)32404-7

19. Hsu PI, Tsai TJ. Epidemiology of upper gastrointestinal damage associated with low-dose aspirin. Curr Pharm Des. 2015; 21(35): 5049-5055. doi: 10.2174/1381612821666150915104800

20. Sostres C, Gargallo CJ, Lanas A. Interaction between Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs and/or low-dose aspirin use: old question new insights. World J Gastroenterol. 2014; 20(28): 9439-9450. doi: 10.3748/wjg.v20.i28.9439

21. Uemura N, Sugano K, Hiraishi H, Shimada K, Goto S, Uchiyama S, et al. Risk factor profiles, drug usage, and prevalence of aspirin-associated gastroduodenal injuries among high-risk cardiovascular Japanese patients: the results from the MAGIC study. J Gastroenterol. 2014; 49(5): 814-824. doi: 10.1007/s00535-013-0839-5

22. Thomopoulos KC, Mimidis KP, Theocharis GJ, Gatopoulou AG, Kartalis GN, Nikolopoulou VN. Acute upper gastrointestinal bleeding in patients on long-term oral anticoagulation therapy: endoscopic findings, clinical management and outcome. World J Gastroenterol. 2005; 11(9): 1365-1368. doi: 10.3748/wjg.v11.i9.1365

23. Rubin TA, Murdoch M, Nelson DB. Acute GI bleeding in the setting of supratherapeutic international normalized ratio in patients taking warfarin: endoscopic diagnosis, clinical management, and outcomes. Gastrointest Endosc. 2003; 58(3): 369-373. doi: 10.1067/S0016-5107(03)00010-5

24. Graham DY, White RH, Moreland LW, Schubert TT, Katz R, Jaszewski R, et al. Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs. Ann Inter Med. 1993; 119(4): 257-262. doi: 10.7326/0003-4819-119-4-199308150-00001

25. Raskin JB, White RH, Jackson JE, Weaver AL, Tindall EA, Lies RB, et al. Misoprostol dosage in the prevention of nonsteroidal anti-inflammatory drug-induced gastric and duodenal ulcers: a comparison of three regimens. Ann Intern Med. 1995; 123(5): 344-350. doi: 10.7326/0003-4819-123-5-199509010-00004

26. Cullen D, Bardhan KD, Eisner M, Kogut DG, Peacock RA, Thomson JM, et al. Primary gastroduodenal prophylaxis with omeprazole for non-steroidal anti-inflammatory drug users. Aliment Pharmacol Ther. 1998; 12(2): 135-140. doi: 10.1046/j.1365-2036.1998.00288.x

27. Ekström P, Carling L, Wetterhus S, Wingren PE, Anker-Hansen O, Lundegårdh G, et al. Prevention of peptic ulcer and dyspeptic symptoms with omeprazole in patients receiving continuous non-steroidal anti-inflammatory drug therapy. A Nordic multicentre study. Scand J Gastroenterol 1996; 31(8): 753-758. doi: 10.3109/00365529609010347

28. Graham DY, Agrawal NM, Campbell DR, Haber MM, Collis C, Lukasik NL, et al. Ulcer prevention in long-term users of nonsteroidal anti-inflammatory drugs. Arch Intern Med. 2002; 162(2): 169-175. doi: 10.1001/archinte.162.2.169

29. Hunt RH, Harper S, Callegari P, Yu C, Quan H, Evans J, et al. Complementary studies of the gastrointestinal safety of the cyclo-oxygenase-2-selective inhibitor etoricoxib. Aliment Pharmacol Ther. 2003; 17(2): 201-210. doi: 10.1046/j.1365-2036.2003.01407.x

30. Hunt RH, Harper S, Watson DJ, Yu C, Quan H, Lee M, et al. The gastrointestinal safety of the COX-2 selective inhibitor etoricoxib assessed by both endoscopy and analysis of upper gastrointestinal events. Am J Gastroenterol. 2003; 98(8): 1725-1733. doi: 10.1111/j.1572-0241.2003.07598.x

31. Karateev AE, Nasonov VA. Development and relapse of gastroduodenal ulcer in patients taking nonsteroid anti-inflammatory drugs: effects of standard risk factors. Terapevticheskiy arkhiv. 2008; 80(5): 62-66. (In Russ.)