Higher quality, large, multicenter RCTs are needed to demonstrate the preventive effect of the two acid-suppressive drugs. Introduction Rationale Low-dose aspirin (LDA) is usually defined as 75C325 mg daily. to December 31, 2013. Randomized controlled trials comparing PPIs and H2RAs for prevention of GI injury associated with low-dose aspirin (LDA) were collected. Two reviewers independently abstracted studies and patient characteristics and appraised study Umeclidinium bromide quality using the Cochrane risk-of-bias tool. Meta-analysis was performed using RevMan 5.1 software. We included nine RCTs involving 1047 patients. The meta-analysis showed that PPIs were superior to H2RAs for prevention of LDA-associated GI erosion/ulcer [odds ratio (OR=0.28, 95% confidence interval (CI): 0.16C0.50] and bleeding (OR=0.28, 95% CI: 0.14C0.59). In conclusion, PPIs were superior to H2RAs for prevention of LDA-related GI erosion/ulcer and bleeding. Higher quality, large, multicenter RCTs are needed to demonstrate the preventive effect of the two acid-suppressive drugs. Introduction Rationale Low-dose aspirin (LDA) is usually defined as 75C325 mg daily. The mechanism of gastrointestinal (GI) injuries associated with LDA can be subdivided into topical and systemic effects. With the widespread use of LDA in primary and secondary prevention of cardiovascular and cerebrovascular diseases, the incidence of LDA-related upper GI injuries, including gastric mucosal erosion, peptic ulcer and bleeding, has increased annually. A retrospective study found that 50% of patients who were long-term LDA users were taking concomitant gastrointestinal protective drugs [1]. Researchers have also found that physicians have poor awareness of LDA-induced GI damage [2], so the prevention of LDA-associated GI injuries has been an important topic for cardiologists and gastroenterologists. Objectives It is well known that proton pump inhibitors (PPIs) reduce the incidence of LDA-associated GI ulcers and bleeding [3C7]. However, concerns about PPICclopidogrel conversation, overprescribing of PPIs [8] and side effects of PPIs [9C11] have increased in recent years. Histamine H2 receptor antagonists (H2RAs) are more cost-effective and safer compared with PPIs. Taha et al. confirmed that standard Umeclidinium bromide doses of famotidine decrease LDA-associated GI injuries and suggested that high-dose H2RAs are an alternative to PPIs to prevent LDA-associated GI bleeding [12]. Rostom et al. pointed out in their systematic review that PPIs were superior to H2RAs for prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastroduodenal ulcer [13]. Only a few studies have investigated prevention of LDA-associated GI ulcers and bleeding, and it has not been established whether H2RAs are a rational alternative to PPIs. The present meta-analysis compared the effect of PPIs and H2RAs for prevention of LDA-related upper GI MAP2K2 injuries, and attempted to provide the best evidence for clinical decision making. Methods The reporting format of this systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement revised in 2009 2009 [14]. Eligibility criteria Inclusion criteria. (1) The design of studies was randomized controlled trials. (2) Patients eligible for inclusion were adults (aged 18 years) who used LDA for at least two continuous weeks. Studies were included regardless of the patients concomitant medication, medical condition and comorbidity. (3) Intervention measures: oral PPIs were used in the experimental group and H2RAs were used as the control drugs. (4) Outcomes of studies: the incidence of LDA-related peptic ulcer and upper GI bleeding in the two groups was observed no matter which was primary endpoint or second endpoint. Exclusion criteria: non-randomized clinical trials, cohort studies, Umeclidinium bromide caseCcontrol studies, pharmacokinetic experiments, and case reports. Search We conducted a comprehensive literature search of PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Chinese National Knowledge Infrastructure (CNKI), WanFang Data and Chinese Biomedical Literature Database (CBM) from their inception to December 31, 2013. Only studies published in English and Chinese were included. The search terms included combinations of the following keywords: aspirin, acetylsalicylic, low-dose aspirin, LDA, proton pump inhibitor, PPI, esomeprazole, pantoprazole, Umeclidinium bromide omeprazole, rabeprazole, lansoprazole, histamine receptor antagonist, H2RA, famotidine, ranitidine, cimetidine, nizatidine, roxatidine, and randomized controlled trial. The search strategy for PubMed as an example is presented below. #1 aspirin OR acetylsalicylic OR low-dose aspirin OR LDA #2 proton pump inhibitor OR PPI OR omeprazole OR esomeprazole OR lansoprazole OR pantoprazole OR rabeprazole #3 histamine receptor antagonist OR H2RA OR famotidine OR ranitidine OR cimetidine OR nizatidine.