Effects of proton pump inhibitors on platelet function in patients receiving clopidogrel: a systematic review

Drug Saf. 2012 Feb 1;35(2):127-39. doi: 10.2165/11594900-000000000-00000.


Background: There is considerable debate regarding the negative impact of concomitant proton pump inhibitor (PPI) therapy on the antiplatelet efficacy of clopidogrel.

Aim: The aim of this study was to perform a systematic review of studies that have evaluated the platelet function of patients receiving clopidogrel alone compared with those receiving both clopidogrel and PPIs.

Methods: We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register in February 2011 for randomized and non-randomized studies that reported platelet function results in patients taking clopidogrel, with or without PPIs.

Results: Our review included 19 studies (13 trials and 6 observational studies) involving 4693 patients. There was considerable heterogeneity in the study designs, patient characteristics, laboratory tests of platelet function, and drug exposure (dose and duration of PPI and clopidogrel). There was some evidence against omeprazole, with five of nine studies demonstrating a significant interaction with clopidogrel. The available platelet function data on esomeprazole (six studies) or pantoprazole (six studies) did not demonstrate a significant interaction. Of the six studies that statistically analysed platelet function data with omeprazole compared with pantoprazole, three showed a significantly greater interaction between omeprazole and clopidogrel, whereas three studies with limited sample sizes were unable to find a significant difference in the effects of omeprazole and pantoprazole.

Conclusion: Platelet function studies do not demonstrate a clear or consistent interaction between clopidogrel and PPIs. These studies are difficult to interpret given the lack of information on drug exposure (dose and duration), variation in laboratory methodology and lack of genetic information. Consequently, platelet function data are of uncertain clinical relevance in determining the risk of an adverse cardiovascular interaction between PPIs and clopidogrel. Clinicians should continue to clinically assess the gastrointestinal risk of the patients and make their prescribing decision for PPIs based on any anticipated benefits in reducing risk of peptic ulcers and gastrointestinal haemorrhage.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Blood Platelets / drug effects*
  • Clopidogrel
  • Drug Interactions
  • Esomeprazole
  • Humans
  • Omeprazole / adverse effects
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / adverse effects*
  • Proton Pump Inhibitors / adverse effects*
  • Randomized Controlled Trials as Topic
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*


  • Platelet Aggregation Inhibitors
  • Proton Pump Inhibitors
  • Clopidogrel
  • Omeprazole
  • Esomeprazole
  • Ticlopidine