The Risks of Thromboembolism Vs. Recurrent Gastrointestinal Bleeding after Interruption of Systemic Anticoagulation in Hospitalized Inpatients With Gastrointestinal Bleeding: A Prospective Study N. Sengupta MD, J.D. Feuerstein MD, V.R. Patwardhan MD, E.B. Tapper MD, G.A. Ketwaroo MD, A.M. Thaker MD and D.A. Leffl er MD, MS R2 전민아 / Prof. 김정욱 The American Journal of GASTROENTEROLOGY, FEBRUARY 2015, Vol 110

Introduction  gastrointestinal bleeding (GIB) & systemic anticoagulation  Patients on systemic anticoagulation have a 4–6% annual risk of developing GIB  Major bleeding on anticoagulation has been associated with a case fatality of rate of 8–10%  Data regarding safety of anticoagulation cessation or continuation after hospitalization for GIB are limited  Existing evidence suggests that there are risks associated with both continuing and discontinuing anticoagulation after GIB · small retrospective study : warfarin was associated with an 8.3% risk of rebleeding · Retrospective cohort study : interruption of warfarin increased the risk of thromboembolic complication and death w/o a significantly increased risk of GIB

Introduction  No clinical guidelines exist on appropriate timing of restarting anticoagulation following admission for GIB  Aim of the study  Compare the rate of major thromboembolic events in patients with GIB whose anticoagulation was discontinued to those patients in whom anticoagulation was resumed at discharge  Determine the rate of readmissions related to recurrent GIB as well as overall mortality within 90 days following the index episode of GIB in both groups of patients

Methods  single-center, prospective, observational cohort study  The study was conducted at Beth Israel Deaconess Medical Center (BIDMC, Boston, MA, USA)  ~  Patients were included evidence of clinically significant GIB  overt hematochezia, hematemesis, melena, or guaiac-positive stools with a significant drop in hemoglobin (hgb)  We obtained baseline demographic information and the following clinical data via medical record review at index hospitalization  We also recorded in-hospital management  Vit K use, transfusion, ICU care

Methods  Endoscopic intervention  Use of epinephrine, clips, electrocautery, or argon plasma coagulation  We categorized patients into whether anticoagulation was resumed or whether there was interruption of anticoagulation  Decision was made by the physicians directly responsible for patient care, depending on clinician and patient preferences  Interruption of anticoagulation was defined as holding systemic anticoagulation for ≥72hr after discharge  An investigator (NS, JDF, or VRP) subsequently contacted all patients by telephone 90 days after discharge

Methods  Thromboembolic event  venous thromboembolism(pulmonary embolism or DVT), arterial thromboembolism, stroke, or transient ischemic attack  Recurrent GIB  readmission to any hospital in the 90-day follow-up period because of another episode of GIB  Patients who developed recurrent GIB within 90 days and were admitted to this hospital were further reviewed to assess the following : admission hgb, transfusion requirements, and need for any endoscopic, radiologic, or surgical intervention  Patients who died during initial hospitalization were excluded

Results 208 : on systemic anticoagulation were admitted with or developed GIB 11(5%) : died during the initial hospitalization 197 included in final analysis 121 continued on systemic anticoagulation at hospital discharge 76 interrupted systemic anticoagulation at hospital discharge treated with the following anticoagulants: warfarin(74%, n =145) enoxaparin (8%, n =15) dabigatran (6%, n =12) rivaroxaban (6%, n =11) unfractionated heparin (6%, n =12) apixaban (1%, n =2)

prevention of A fib-related stroke or embolization Patients continued on anticoagulation at discharge were more likely to have a history of a prosthetic valve, prior stroke or transient ischemic attack or prior history of GIB Patients with anticoagulation interruption were more likely to have a history of active malignancy 63% required red blood cell transfusion need for endoscopic intervention during initial hospitalizationwas not associated with group assignment

Results : 90-Day outcomes: thromboembolic events  Only 12% of the original cohort was lost to follow-up before the 90-day study call  During the 90-day follow-up period after hospital discharge, 7(4%) patients developed a thromboembolic event  1 of 121(0.8%) patients who resumed anticoagulation  6 of 76 patients (8%) who had interruption or cessation of anticoagulation  3 DVT  3 stroke  1 Pulmonary embolism  All seven of the patients with thromboembolic episodes required blood transfusion during their index hospitalization

Results : 90-Day outcomes: thromboembolic events Patients with an active malignancy at the time of their GIB were more likely to have a thrombotic episode Need for endoscopic intervention during initial hospitalization was not associated with having recurrent GIB

Results : 90-Day outcomes: thromboembolic events Anticoagulation continuation was independently associated on multivariate regression with a lower risk of major thrombotic episodes within 90 days

Results : 90-Day outcomes: thromboembolic events  Time-to-outcome analysis according to resuming anticoagulation at original discharge

Results : 90-Day outcomes: recurrent GIB  During the 90-day follow-up period, 27 patients (14%) were readmitted with recurrent GIB with a median time to readmission of 13 days  22 patients who resumed anticoagulation  5 patients who had interruption or cessation of anticoagulation  Anticoagulation continuation at discharge was not significantly associated with an increased risk of recurrent GIB at 90 days Resuming anticoagulation at hospital discharge was associated with a higher rate of readmissions because of GIB within 90days, although this result did not reach statistical significance

Results : 90-Day outcomes: recurrent GIB only 36% had a drop in hgb greater than 1 g/dL compared with their discharge hgb levels only 5 (19%) patients required endoscopic, radiographic, or surgical intervention to manage their recurrent GIB

Results : 90-Day outcomes: mortality  During the 90-day follow-up period, 16 (8%) patients died within 90 days of discharge  All deaths in the cohort were unrelated to recurrent GIB or thrombotic events  There was no significant difference in mortality at 90 days for patients who had their anticoagulation resumed at hospital discharge

Conclusion  Restarting anticoagulation at discharge after GIB was associated with fewer thromboembolic events without a significantly increased risk of recurrent GIB at 90 days  The benefits of continuing anticoagulation at discharge may outweigh the risks of recurrent GIB  These data support the recommendation that anticoagulation should be continued after an episode of GIB whenever possible