Gastrointestinal bleeding risk of non-vitamin K antagonist oral anticoagulants versus warfarin in general and after polypectomy: a population-based study with propensity score matching analysis

다국어 초록 (Multilingual Abstract)

Background/Aims: Gastrointestinal bleeding (GIB) risk for non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin is largely unknown. We aimed to determine the risk of overall and post-polypectomy GIB for NOACs and warfarin. Methods: Using the Korean National Health Insurance database, we created a cohort of patients who were newly prescribed NOACs or warfarin between July 2015 and December 2017 using propensity score matching (PSM). Kaplan-Meier analysis with log-rank test was performed to compare the risk of overall and post-polypectomy GIB between NOACs (apixaban, dabigatran, and rivaroxaban) and warfarin. Post-polypectomy GIB was defined as bleeding within 1 month after gastrointestinal endoscopic polypectomy.Results: Out of 234,206 patients taking anticoagulants (187,687 NOACs and 46,519 warfarin), we selected 39,764 pairs of NOACs and warfarin users after PSM. NOACs patients showed significantly lower risk of overall GIB than warfarin patients (log-rank <i>P</i><0.001, hazard ratio, 0.86; 95% confidence interval, 0.78–0.94; <i>P</i>=0.001). Among NOACs, apixaban showed the lowest risk of GIB. In the subgroup of 7,525 patients who underwent gastrointestinal polypectomy (lower gastrointestinal polypectomy 93.1%), 1,546 pairs were chosen for each group after PSM. The NOACs group showed a high risk of post-polypectomy GIB compared with the warfarin group (log-rank <i>P</i>=0.001, hazard ratio, 1.97; 95% confidence interval, 1.16–3.33; <i>P</i>=0.012).Conclusions: This nationwide, population-based study demonstrates that risk of overall GIB is lower for NOACs than for warfarin, while risk of post-polypectomy GIB is higher for NOACs than for warfarin.

참고문헌 (Reference)

1 Nagata N, "Therapeutic endoscopy-related GI bleeding and thromboembolic events in patients using warfarin or direct oral anticoagulants : results from a large nationwide database analysis" 67 : 1805-1812, 2018

2 ASGE Standards of Practice Committee, "The management of antithrombotic agents for patients undergoing GI endoscopy" 83 : 3-16, 2016

3 Brodie MM, "Severity of gastrointestinal bleeding in patients treated with direct-acting oral anticoagulants" 131 : 573-579, 2018

4 Patel MR, "Rivaroxaban versus warfarin in nonvalvular atrial fibrillation" 365 : 883-891, 2011

5 Lau LH, "Risks of post-colonoscopic polypectomy bleeding and thromboembolism with warfarin and direct oral anticoagulants : a population-based analysis" 71 : 100-110, 2022

6 Lanas Á, "Risk of upper and lower gastrointestinal bleeding in patients taking nonsteroidal anti-inflammatory drugs, antiplatelet agents, or anticoagulants" 13 : 906-912, 2015

7 Washio E, "Proton pump inhibitors increase incidence of nonsteroidal anti-inflammatory drug-induced small bowel injury: a randomized, placebo-controlled trial" 14 : 809-815, 2016

8 Yanagisawa N, "Post-polypectomy bleeding and thromboembolism risks associated with warfarin vs direct oral anticoagulants" 24 : 1540-1549, 2018

9 Mega JL, "Pharmacology of antithrombotic drugs : an assessment of oral antiplatelet and anticoagulant treatments" 386 : 281-291, 2015

10 Abraham NS, "Novel anticoagulants : bleeding risk and management strategies" 29 : 676-683, 2013

11 Holster IL, "New oral anticoagulants increase risk for gastrointestinal bleeding : a systematic review and meta-analysis" 145 : 105-112, 2013

12 Kirley K, "National trends in oral anticoagulant use in the United States, 2007 to 2011" 5 : 615-621, 2012

13 Chan FKL, "Management of patients on antithrombotic agents undergoing emergency and elective endoscopy : joint Asian Pacific Association of Gastroenterology(APAGE)and Asian Pacific Society for Digestive Endoscopy(APSDE)practice guidelines" 67 : 405-417, 2018

14 Adeboyeje G, "Major bleeding risk during anticoagulation with warfarin, dabigatran, apixaban, or rivaroxaban in patients with nonvalvular atrial fibrillation" 23 : 968-978, 2017

15 Tien A, "Impact of direct-acting oral anticoagulants and warfarin on postendoscopic GI bleeding and thromboembolic events in patients undergoing elective endoscopy" 92 : 284-292, 2020

16 Feagins LA, "GI bleeding risk of DOACs versus warfarin : is newer better?" 63 : 1675-1677, 2018

17 Cha JM, "Features of postcolonoscopy colorectal cancer and survival times of patients in Korea" 17 : 786-788, 2019

18 Niikura R, "Factors predicting adverse events associated with therapeutic colonoscopy for colorectal neoplasia : a retrospective nationwide study in Japan" 84 : 971-982, 2016

19 Cheol Seong S, "Data resource profile : the National Health Information Database of the National Health Insurance Service in South Korea" 46 : 799-800, 2017

20 Connolly SJ, "Dabigatran versus warfarin in patients with atrial fibrillation" 361 : 1139-1151, 2009

21 RuffCT, "Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation : a meta-analysis of randomised trials" 383 : 955-962, 2014

22 Abraham NS, "Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin : population based cohort study" 350 : h1857-, 2015

23 Joseph DA, "Colorectal cancer screening : estimated future colonoscopy need and current volume and capacity" 122 : 2479-2486, 2016

24 Kohsaka S, "Bleeding risk of apixaban, dabigatran, and low-dose rivaroxaban compared with warfarin in Japanese patients with non-valvular atrial fibrillation: a propensity matched analysis of administrative claims data" 33 : 1955-1963, 2017

25 Ray WA, "Association of oral anticoagulants and proton pump inhibitor cotherapy with hospitalization for upper gastrointestinal tract bleeding" 320 : 2221-2230, 2018

26 Granger CB, "Apixaban versus warfarin in patients with atrial fibrillation" 365 : 981-992, 2011

27 Cangemi DJ, "A comparison of the rate of gastrointestinal bleeding in patients taking non-vitamin K antagonist oral anticoagulants or warfarin" 112 : 734-739, 2017