title: Proton pump inhibitor monotherapy and the risk of cardiovascular events in patients with gastro-esophageal reflux disease: a meta-analysis.
abstract: OBJECTIVE
  Proton pump inhibitors (PPIs) are commonly used as potent gastric acid secretion antagonists for gastro-esophageal disorders and their overall safety in patients with gastro-esophageal reflux disease (GERD) is considered to be good and they are well-tolerated. However, recent studies have suggested that PPIs may be a potential independent risk factor for cardiovascular adverse events. The aim of our meta-analysis was to examine the association between PPI monotherapy and cardiovascular events in patients with GERD.
  
  
  METHODS
  A literature search involved examination of relevant databases up to July 2015 including PubMed, Cochrane Library, EMBASE, and ClinicalTrial.gov, as well as selected randomized controlled trials (RCTs) reporting cardiovascular events with PPI exposure in GERD patients. In addition, the pooled risk ratio (RR) and heterogeneity were assessed based on a fixed effects model of the meta-analysis and the I2statistic, respectively.
  
  
  RESULTS
  Seventeen RCTs covering 7540 patients were selected. The pooled data suggested that the use of PPIs was associated with a 70% increased cardiovascular risk (RR=1.70, 95% CI: [1.13-2.56], P=.01, I2=0%). Furthermore, higher risks of adverse cardiovascular events in the omeprazole subgroup (RR=3.17, 95% CI: [1.43-7.03], P=.004, I2=25%) and long-term treatment subgroup (RR=2.33, 95% CI: [1.33-4.08], P=.003, I2=0%) were found.
  
  
  CONCLUSIONS
  PPI monotherapy can be a risk factor for cardiovascular adverse events. Omeprazole could significantly increase the risk of cardiovascular events and, so, should be used carefully.
authors: Shenyang Pharmaceutical University, Shenyang, China.
authors: S
authors: S
authors: Sun
authors: Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, China.
authors: Z
authors: Z
authors: Cui
authors: Shenyang Pharmaceutical University, Shenyang, China.
authors: M
authors: M
authors: Zhou
authors: Shenyang Pharmaceutical University, Shenyang, China.
authors: R
authors: R
authors: Li
authors: Shenyang Pharmaceutical University, Shenyang, China.
authors: H
authors: H
authors: Li
authors: Shenyang Pharmaceutical University, Shenyang, China.
authors: S
authors: S
authors: Zhang
authors: Shenyang Pharmaceutical University, Shenyang, China.
authors: Y
authors: Y
authors: Ba
authors: Shenyang Pharmaceutical University, Shenyang, China.
authors: G
authors: G
authors: Cheng
mesh_terms: D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000453:epidemiology*; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D009853:Omeprazole / Q000008:administration & dosage / Q000009:adverse effects; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012307:Risk Factors
chemical_list: D005765:Gastrointestinal Agents; D054328:Proton Pump Inhibitors; D009853:Omeprazole
keywords: cardiovascular events; gastro-esophageal reflux disease; meta-analysis; proton pump inhibitors