Management of Acute Upper Gastrointestinal Bleeding in Recent Acute Coronary Syndrome Patients by Early Endoscopy and Non-Endoscopy Treatment: A Randomized Controlled Trial to Evaluate Efficacy and Safety

MATERIALS AND METHODS Study Design and Randomization A multicenter RCT of recent ACS patients presenting with acute UGIB was conducted in three tertiary centers (Far Eastern Memorial Hospital, Hsin-Chu Branch and Taipei Branch of National Taiwan University Hospital) in Taiwan. Patients with recent ACS, including unstable angina (UA), ST-elevation MI (STEMI) and non-ST elevation MI (NSTEMI) who presented symptoms of acute UGIB were evaluated for enrollment. The inclusion criteria were as follows: 1) age over 20-year-old, 2) ACS episodes in the past 2 weeks, 3) symptoms of UGIB including hematemesis, coffee ground emesis or tarry stool passage accompanied with a decrease in hemoglobin (Hb) level greater than 2 g/dl from baseline. Patients with any one of the following criteria were excluded: 1) malignancy or other advanced disease with a life expectancy of < 6 months, 2) pregnant or lactating women, 3) history of allergy or severe side effects from PPIs, contrast, and iodine, 4) platelet count < 80k/uL, or prothrombin time INR >2.0, 5) decompensated (Child-Turcotte-Pugh score B and C) liver cirrhosis, 6) stage 3~5 chronic kidney disease (CKD) (estimated Ccr < 60 ml/min/1.73m2) using Cockcroft-Gault formula, exclusive of end-stage renal disease under renal replacement therapy.17 All the authors had access to the study data and had reviewed and approved the final manuscript.

Eligible patients were randomly assigned to EE or non-EE management. Patients in both groups received bolus intravenous pantoprazole 40mg followed by continuous infusion (8mg/hour).3,18 In the EE group, patients underwent endoscopy within 24 hours after onset of UGIB symptoms. All enrolled patients were monitored in cardiac intensive care unit. At endoscopy, stigmata of hemorrhage (SRH) were treated by endoscopic therapy in combination of any two of the followings: epinephrine submucosal injection, thermocoagulation, hemoclipping, and argon plasma coagulation. Hemostasis was considered initial successful if bleeding had stopped at endoscopy. Antral-biopsy specimens were obtained to a rapid urease test and histopathological examination for Helicobacter pylori (Hp) study. Patients assigned to non-EE group received medical treatment with PPIs alone and underwent esophagogastroduodenoscopy two weeks after enrollment to evaluate the recent SRH. Decision on discontinuation of DAPT was at the discretion of cardiologists depending on cardiac conditions of each enrolled patient.

Study Endpoints The primary endpoint was failure of control hemorrhage. The secondary endpoints included complication rate, length of hospital stay, units of blood transfusion, re-bleeding rate, needs for repeated intervention (endoscopic therapy, transarterial embolization (TAE), or surgery) for uncontrollable recurrent bleeding. Blood troponin-T, creatine kinase-MB, Hb, hematocrit (Hct) and complete electrocardiogram (ECG) were checked every 8 hours within 24 hours after enrollment. APACHE II, Rockall and Blatchford scores at intervention were calculated.19 This study was approved by the Research Ethics Review Committee of study institutes (FEMH IRB-103062-F, Hsin-Chu NTUH 105-001-F, Yun-Lin NTUH 201411020RIND).

Definition of failure to control hemorrhage The time frame for acute bleeding episode was defined as 24 hours after enrollment. Clinical failure of control bleeding was defined as: hematemesis or nasogastric tube drainage of significant fresh blood (≥ 200 mL) ≥ 2hours, or persistent hypovolemic shock after intervention; or 3 g/dl drop in Hb level (or 9% drop of Hct) within 24 hours if no blood transfusion; or a decrease in Hb ≥ 2 g/dL or an increase ≤ 1 g/dL, despite 2 or more units of red blood cells (RBC) component transfusion within 24 hours.

Definition of re-bleeding: