Proton pump inhibitor monotherapy and the risk of cardiovascular events in patients with gastro‐esophageal reflux disease: a meta‐analysis

Background and Purpose Proton pump inhibitors ( PPI s) 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 PPI s 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 ( RCT s) 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 I 2 statistic, respectively. Key Results Seventeen RCT s covering 7540 patients were selected. The pooled data suggested that the use of PPI s was associated with a 70% increased cardiovascular risk ( RR =1.70, 95% CI : [1.13–2.56], P =.01, I 2 =0%). Furthermore, higher risks of adverse cardiovascular events in the omeprazole subgroup ( RR =3.17, 95% CI : [1.43–7.03], P =.004, I 2 =25%) and long‐term treatment subgroup ( RR =2.33, 95% CI : [1.33–4.08], P =.003, I 2 =0%) were found. Conclusion & Inferences 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.