Efficacy and safety of preventive treatments with proton pump inhibitors and histamine 2 receptor antagonists for stress ulcer bleeding in postoperative patients: a Meta-analysis

Abstract

Objective To evaluate the efficacy and safety of preventive treatments with proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) for stress ulcer bleeding (SUB) in postoperative patients. Methods The Cochrane library, Medline, Embase, CBM, CNKI, VIP, Wan Fang Data etc. were searched from the inception to March 2016. Randomized controlled trials (RCT) and quasi-RCT (qRCT) of preventive treatments with PPI and H2RA for SUB were collected. Inclusion criteria was any of the following outcome measures: (1) incidence of SUB, (2) SUB-related morbidity, (3) gastric juice pH, (4) hospital days, (5) hospital days in ICU, (6) adverse reactions related to SUB treatments with PPI or H2RA. Quality of methodology was evaluated using bias risk assessment tool from Cochrane collaboration networks. Meta-analysis was performed using RevMan 5.3 software and the results were expressed as relative risk (RR) and its 95% confidence interval (CI). Rating quality of evidence for outcome measures was assessed using the Grading of Recommendations Assessment Development and Evaluation (GRADE). Results A total of 14 RCTs and 1 qRCT were entered into this study and 1 334 patients were involved. Of the 1 334 patients, 653 were in the experimental group (PPI group) and 681 were in the control group (H2RA group). The overall quality of the 15 studies was lower. Randomization and double-blinding methods were applied only in one study, no allocation concealment methods were used, and patients′s loss to follow-up or withdrawal from the trial was not reported in any of the 15 studies. The funnel plot of SUB and SUB-related morbidity showed no significant publication bias. Meta-analysis showed that the incidences of SUB were 5.1% (25/493) and 17.7% (92/521) in the PPI group and H2RA group, respectively; there was statistically significant difference between the 2 groups [RR=0.33, 95%CI: 0.22-0.49; P<0.01]. The SUB-related morbidity was 0.6% (2/328) and 2.2% (8/359) in the PPI group and H2RA group, respectively; there was no statistically significant difference between the 2 groups [RR=0.39, 95%CI: 0.12-1.30; P=0.12]. Adverse drug reactions (ADR) were reported in 2 studies. The ADR incidences were 3.2% (1/31) and 6.1% (2/33) in the PPI and H2RA groups, respectively in 1 of the 2 studies [RR=0.53, 95%CI: 0.05-5.58, P=0.60] and no ADR was reported in the other study. Conclusions PPI was superior to H2RA in preventing SUB, but there was no statistically significant difference in the SUB-related morbidity in patients with PPI and H2RA treatments. The incidence of adverse reactions of PPI and H2RA was low and mild. Key words: Proton pump inhibitor; Histamine 2 receptor antagonists; Meta-analysis; Stress ulcer