Comparison of the Effects of Warfarin and Direct Oral Anticoagulants in Upper Gastrointestinal System Bleeding

Abstract

Background This study aimed to compare the frequency of use of new-generation oral anticoagulants or warfarin in patients presenting to our hospital with upper gastrointestinal system bleeding and to determine the rates of recurrent upper gastrointestinal system bleeding. Methods In this cross-sectional study, the data of 346 patients who applied to Samsun Research and Training Hospital between 01.01.2021 and 31.12.2021 and were hospitalized by Internal Medicine and Gastroenterology clinics with a diagnosis of upper gastrointestinal tract bleeding or who underwent outpatient endoscopy were examined retrospectively. Patients who experienced recurrent upper GI bleeding were identified. The frequency of direct oral anticoagulant drug usage in patients with recurrent bleeding was determined, and data such as rebleeding rate, length of hospital stay, transfusion requirement, and mortality were analyzed between the groups of patients who did not use the drug and those who did. Results Of 346 patients included in the study, 151 (43.6%) were female, 195 (56.4%) were male, and the mean age was 68.8±15.8 years. When the frequencies of drug usage that could create a risk of bleeding were examined, it was found that 107 (30.9%) used nonsteroidal anti-inflammatory drugs, 102 (29.5%) used acetylsalicylic acid, 65 (18.8%) used direct oral anticoagulants, 58 (16.8%) used clopidogrel, and 19 (5.5%) used warfarin. When the frequencies of drug usage that could create a risk of bleeding were compared according to recurrent bleeding and mortality status, it was found that the groups were statistically similar. Conclusion There was no difference in the frequency of recurrent upper gastrointestinal bleeding between the patients using warfarin and direct oral anticoagulants. When the patients were divided into two groups according to the incidence of recurrent gastrointestinal bleeding and compared in terms of age, gender, comorbid conditions that could cause bleeding, drug usage, and mortality, there was no statistically significant difference between the groups. More comprehensive studies are needed on this subject.

Keywords

• : Gastrointestinal system
• oral anticoagulant
• recurrent bleeding

References

1. Laine L, Yang H, Chang SC. Trends for incidence of hospitalization and due to GI complications in the United States from 2001 to 2009. Am J Gastroenterol. 2012;107:1190-1195. doi: 10.1038/ajg.2012.110.
2. Feldman M, Friedmann LS, Sleisenger MH. Sleisenger & Fordtran's Gastrointestinal and Liver Disease: pathophysiology, diagnosis, management. 7th ed. Philadelphia: Saunders; 2002. p.211-243.
3. Lee JG. What is the value of early endoscopy in upper gastrointestinal bleeding? Nat Clin Pract Gastroenterol Hepatol. 2006;3:534-535. doi: 10.1038/ncpgasthep0623.
4. Szura M, Pasternak A. Upper non-variceal gastrointestinal bleeding - review the effectiveness of endoscopic hemostasis methods. World J Gastrointest Endosc. 2015;7(13):1088-1095. doi: 10.4253/wjge.v7.i13.1088.
5. Guerrouij M, Uppal CS, Alklabi A, Douketis JD. The clinical impact of bleeding during oral anticoagulant therapy: assessment of morbidity, mortality and post-bleed anticoagulant management. J Thromb Thrombolysis. 2011;31(4):419-423. doi: 10.1007/s11239-010-0522-x.
6. Gedikli Ö, Altay S, Ünlü S, Çakmak HA, Aşkın L, Yanık A, Baycan ÖF, Avcı İİ, Gürel YE, Gürel OM. Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study. Anatol J Cardiol. 2021;25:196-204. doi: 10.14744/AnatolJCardiol.2020.00516.
7. Coleman CI, Sobieraj DM, Winkler S, Cutting P, Mediouni M, Alikhanov S, Kluger J. Effect of pharmacological therapies for stroke prevention on major gastrointestinal bleeding in patients with atrial fibrillation. Int J Clin Pract. 2012;66(1):53-63. doi: 10.1111/j.1742-1241.2011.02809.x.
8. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Husted S, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-992. doi: 10.1056/NEJMoa1107039.

9. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-1151. doi: 10.1056/NEJMoa0905561.
10. Laine L. Bleeding with direct oral anticoagulants: The gastrointestinal tract and beyond. Clin Gastroenterol Hepatol. 2017;15(11):1665-1667. doi: 10.1016/j.cgh.2017.06.036.
11. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883-891. doi: 10.1056/NEJMoa1009638.
12. Miller CS, Grandi SM, Shimony A, Filion KB, Eisenberg MJ. Meta-analysis of efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus warfarin in patients with atrial fibrillation. Am J Cardiol. 2012;110(3):453-460. doi: 10.1016/j.amjcard.2012.03.049.
13. Rajan D, Bonde AN, Olesen JB, Lamberts M, Lip GYH, Pedersen CT, Torp-Pedersen C, Gislason GH. Resumption of anticoagulant treatment in patients with atrial fibrillation following gastrointestinal bleeding: a nationwide cohort study. Eur Heart J. 2019;40(Supplement_1). doi: 10.1093/eurheartj/ehz748.0214.
14. Hernandez I, Zhang Y, Brooks MM, Chin PKL, Saba S. Anticoagulation use and clinical outcomes after major bleeding on dabigatran or warfarin in atrial fibrillation. Stroke. 2017;48(1):159-166. doi: 10.1161/STROKEAHA.116.015652.
15. Türedi S, Gündüz A, Yandı M. Etiological and prognostic evaluation of patients with upper gastrointestinal system bleeding presenting to the emergency department of Karadeniz Technical University Faculty of Medicine. Turk J Emerg Med. 2010;10(1):20-25.
16. Anthony T, Penta P, Todd RD, Sarosi GA, Nwariaku F, Rege RV. Rebleeding and survival after acute lower gastrointestinal bleeding. Am J Surg. 2004;188(5):485-490. doi: 10.1016/j.amjsurg.2004.07.028.
17. Stanley AJ, Laine L, Dalton HR, Ngu JH, Schultz M, Abazi R, Zakko L, Thornton S, Wilkinson K, Khor CJ, Murray IA, Laursen SB. Comparison of risk scoring systems for patients presenting with upper gastrointestinal bleeding: an international multicentre prospective study. BMJ. 2017;356:j6432. doi: 10.1136/bmj.j6432.
18. Boonpongmanee S, Fleischer DE, Pezzullo JC, Collier K, Mayoral W, Al-Kawas FH, Smith RE. The frequency of peptic ulcers as a cause of upper GI bleeding is exaggerated. Gastrointest Endosc. 2004;59(7):788-794. doi: 10.1016/S0016-5107(04)00188-4.
19. Van Leerdam ME, Vreeburg EM, Rauws EAJ, Geraedts AAM, Tijssen JGP, Reitsma JB, Tytgat GN, Dekker E. Acute upper GI bleeding: did anything change? Time trend analysis of incidence and outcome of acute upper GI bleeding between 1993/1994 and 2000. Am J Gastroenterol. 2003;98(7):1494-1499. doi: 10.1111/j.1572-0241.2003.07461.x.
20. Dicu D, Pop F, Ionescu D, Dicu T. Comparison of risk scoring systems in predicting clinical outcome at upper gastrointestinal bleeding patients in an emergency unit. Am J Emerg Med. 2013;31(1):94-99. doi: 10.1016/j.ajem.2012.07.035.
21. Gölgeli H, Ecirli Ş, Kutlu O, Başer H, Karasoy D. Evaluation of patients with upper gastrointestinal system bleeding. Dicle Med J. 2014;41(3):495-501. doi: 10.5798/diclemedj.0921.2014.03.0455.
22. Tatlıparmak AC, Dikme Ö, Dikme Ö, Topaçoğlu H. Cancer, platelet distribution width, and total protein levels as predictors of rebleeding in upper gastrointestinal bleeding. PeerJ. 2022;10:e13837. doi: 10.7717/peerj.13837.
23. Brodie MM, Newman JC, Smith T, Rockey DC. Severity of gastrointestinal bleeding in patients treated with direct-acting oral anticoagulants. Am J Med. 2018;131(5):573.e9-573.e15. doi: 10.1016/j.amjmed.2017.10.040.
24. Fukuda S, Shimodaira Y, Watanabe K, Takahashi S, Sugawara K, Suzuki Y, Tanaka T, Sugimoto K. Risks for rebleeding and in-hospital mortality after gastrointestinal bleeding in a tertiary referral center in Japan. Digestion. 2020;101(1):31-37. doi: 10.1159/000504262.
25. Pálinkás D, Teutsch B, Gagyi EB, Engh MA, Kalló P, Veres DS, Márton G, Török M. No association between gastrointestinal rebleeding and DOAC therapy resumption: a systematic review and meta-analysis. Biomedicines. 2023;11(2):520. doi: 10.3390/biomedicines11020520.
26. Candeloro M, van Es N, Cantor N, Schulman S, Carrier M, Ageno W, Monreal M, Becattini C. Recurrent bleeding and thrombotic events after resumption of oral anticoagulants following gastrointestinal bleeding: Communication from the ISTH SSC Subcommittee on Control of Anticoagulation. J Thromb Haemost. 2021;19(10):2618-2628. doi: 10.1111/jth.15445.