title: Adverse cardiovascular effects of concomitant use of proton pump inhibitors and clopidogrel in patients with coronary artery disease: a systematic review and meta-analysis.
abstract: OBJECTIVE
  Conclusions from clinical studies and previous meta-analyses were inconsistent regarding the cardiovascular effects of concomitant use of proton pump inhibitors (PPIs) and clopidogrel. As new studies are constantly emerging, we performed this meta-analysis to further assess the cardiovascular effects of concomitant use of PPIs and clopidogrel with a focus on individual PPIs.
  
  
  METHODS
  A systematic electronic literature search was conducted in EMBASE, MEDLINE, PubMed and Chinese Biomedical Literature Database (CBM) to identify the studies reporting on the association of concomitant use of PPIs and clopidogrel with adverse cardiovascular outcomes. A hand search of reference lists was performed to identify further studies. Only studies published in English or Chinese were included in this review.
  
  
  RESULTS
  Twenty seven full-text articles and five abstracts with 159,998 patients were included in meta-analysis. Concomitant use of PPIs and clopidogrel is associated with an increased risk of major cardiovascular events (MACE) (HR 1.40, 95% CI 1.19-1.64; OR 1.27, 95% CI 1.13-1.42) and acute coronary syndrome (HR 1.42, 95% CI 1.14-1.77; OR 1.42, 95% CI 1.08-1.87) but not with all-cause mortality (HR 1.30, 95% CI 0.91-1.86; OR 0.92, 95% CI 0.82-1.04), cardiovascular death (HR 1.21, 95% CI 0.60-2.43) and stent thrombosis (HR 1.52, 95% CI 0.87-2.65). In the analyses of individual PPIs, none of the PPIs is associated with an increased MACE risk except for pantoprazole (HR 1.52, 95% CI 1.18-1.94).
  
  
  CONCLUSIONS
  Concomitant use of PPIs and clopidogrel in patients with coronary artery disease is associated with an increased risk of MACE or acute coronary syndrome, but there is insufficient evidence to conclude that there is an interaction between individual PPIs and clopidogrel.
authors.affiliation: Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Baotao
authors.initials: B
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.forename: Hongmei
authors.initials: H
authors.lastname: Yao
authors.forename: Xianchao
authors.initials: X
authors.lastname: Jing
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.forename: Jing
authors.initials: J
authors.lastname: Li
mesh_terms: D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D054328:Proton Pump Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine