628 Proton Pump Inhibitors or Histamine-2 Receptor Antagonist Co-Therapy Decrease the Risk of Upper Gastrointestinal Bleeding in Patients on Direct Oral Anticoagulation: A Systematic Review and Meta-Analysis

Abstract

INTRODUCTION: Direct oral anticoagulation (DOAC) has gained more universal acceptance for use in patients with venous thrombosis or atrial fibrillation because of its safety profile and the elimination of drug monitoring. However, upper gastrointestinal bleeding (UGIB) is a major complication, especially in those with higher bleeding risk. Recent studies have reported a decreased risk of UGIB in patients using DOAC with proton pump inhibitors (PPI) or histamine-2 receptor (H2RA) but the results are controversial. We aimed to assess the effect of PPI or H2RA co-therapy with DOAC on the risk of UGIB by a systematic review and meta-analysis. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2019. Included studies were cohort (prospective or retrospective) studies that investigated the incidence of UGIB comparing between DOAC with and without PPI or H2RA co-therapy. Upper gastrointestinal bleeding is defined as melena or hematemesis that required hospitalization. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate pooled risk ratio (RR) and 95% confidence intervals. RESULTS: Six studies from 2015 to 2018 were included in this meta-analysis and reported a total of 469,593 patients using DOAC. Mean age was more than 70 years. Proton pump inhibitors co-therapy and histamine-2 receptor antagonist co-therapy significantly decreased the incidence of UGIB in DOAC users (pooled RR 0.58 (0.45-0.74), P < 0.001, I2 = 0.0% and 0.63 (0.42-0.96), P = 0.033, I2 = 0.0% respectively) (Figure1 and 2). Three studies reported PPI plus H2RA co-therapy with DOAC decreased the incidence of UGIB but it is not statistically significance (pooled RR 0.71 (0.18-2.74), P = 0.616, I2 = 88.5%) (Figure 3). CONCLUSION: Our study demonstrated statistically significant benefit of the combination either PPI or H2RA co-therapy with DOAC to lower the incidence of UGIB. However, the combination of PPI and H2RA did not decrease the risk of bleeding. Randomized controlled trials studies are needed to further evaluate this association.