title: Should patients prescribed long-term low-dose aspirin receive proton pump inhibitors? A systematic review and meta-analysis.
abstract: BACKGROUND
  Several clinical guidelines recommend the use of proton pump inhibitors (PPIs) in patients taking low-dose aspirin but report no or limited supporting data. We conducted a systematic review and meta-analysis to examine the effects of co-administration of PPIs in patients taking low-dose aspirin on the risks of adverse gastrointestinal (GI) and cardiovascular (CV) events, and on patient adherence to aspirin.
  
  
  METHODS
  We searched PUBMED, EMBASE and Cochrane Central Register of Controlled Trials databases for relevant articles published through November 2013. We included randomised controlled trials (RCTs) and observational studies in patients taking low-dose aspirin with and without PPIs. Risk of bias was assessed using the Cochrane Collaboration's tool (for RCTs) and the Newcastle-Ottawa Scale (for observational studies). Pooled risk ratios (RRs) were computed using a random-effects model.
  
  
  RESULTS
  We included 13 studies, of which 12 (2 RCTs and 10 observational studies) reported on GI events, and one (cohort study) on both GI bleeding and CV events. No study reported on adherence to aspirin. Co-administration of PPIs in patients receiving low-dose aspirin was associated with risk reductions of 73% (RR 0.27, 95% CI 0.17-0.42) and 50% (RR 0.50, 95% CI 0.32-0.80) in the occurrence of peptic ulcer and GI bleeding respectively. There was evidence of bias in publications reporting on the GI events.
  
  
  CONCLUSIONS
  The practice of co-prescribing PPIs in patients taking low-dose aspirin is supported by some data, but the evidence is rather weak. It currently remains unclear whether the benefits of co-administration of PPIs in users of low-dose aspirin outweigh their potential harms.
authors.affiliation: Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, Maastricht, The Netherlands.|Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Tran-Duy
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: F H
authors.initials: FH
authors.lastname: Vanmolkot
authors.affiliation: Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Joore
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: A W
authors.initials: AW
authors.lastname: Hoes
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.|CARIM School for Cardiovascular Diseases, Maastricht UMC+, Maastricht, the Netherlands.
authors.forename: C D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001241:Aspirin / Q000008:administration & dosage*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control; D014943:Global Health; D006801:Humans; D015994:Incidence; D011379:Prognosis; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D012307:Risk Factors; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D054328:Proton Pump Inhibitors; D001241:Aspirin