+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: an updated meta-analysis



Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: an updated meta-analysis



Open Heart 2(1): E000248



Dual antiplatelet therapy is the standard of care after coronary stent placement but increases the bleeding risk. The effects of proton pump inhibitors (PPIs) on clopidogrel metabolism have been described, but the clinical significance is not yet definitive. We aimed to do an updated meta-analysis comparing outcomes in patients receiving clopidogrel with and without PPIs. We systematically searched PubMed, Scopus and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) and controlled observational studies in patients taking clopidogrel stratified by concomitant PPI use. Heterogeneity was examined with the Cochran Q test and I(2) statistics; p values inferior to 0.10 and I(2) >25% were considered significant for heterogeneity. We included 39 studies with a total of 214 851 patients, of whom 73 731 (34.3%) received the combination of clopidogrel and a PPI. In pooled analysis, all-cause mortality, myocardial infarction, stent thrombosis and cerebrovascular accidents were more common in patients receiving both drugs. However, among 23 552 patients from eight RCTs and propensity-matched studies, there were no significant differences in mortality or ischaemic events between groups. The use of PPIs in patients taking clopidogrel was associated with a significant reduction in the risk of gastrointestinal bleeding. The results of our meta-analysis suggest that PPIs are a marker of increased cardiovascular risk in patients taking clopidogrel, rather than a direct cause of worse outcomes. The pharmacodynamic interaction between PPIs and clopidogrel most likely has no clinical significance. Furthermore, PPIs have the potential to decrease gastrointestinal bleeding in clopidogrel users.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 058091941

Download citation: RISBibTeXText

PMID: 26196021

DOI: 10.1136/openhrt-2015-000248


Related references

Cardiovascular and gastrointestinal events of three antiplatelet therapies: clopidogrel, clopidogrel plus proton-pump inhibitors, and aspirin plus proton-pump inhibitors in patients with previous gastrointestinal bleeding. Journal of Gastroenterology 46(1): 39-45, 2011

Meta-analysis: the effects of proton pump inhibitors on cardiovascular events and mortality in patients receiving clopidogrel. Alimentary Pharmacology and Therapeutics 31(8): 810-823, 2010

Effects of proton pump inhibitors on adverse gastrointestinal events in patients receiving clopidogrel: systematic review and meta-analysis. Drug Safety 34(1): 47-57, 2011

A comparison of aspirin and clopidogrel with or without proton pump inhibitors for the secondary prevention of cardiovascular events in patients at high risk for gastrointestinal bleeding. Clinical Therapeutics 31(9): 2038-2047, 2009

Combination Use of Clopidogrel and Proton Pump Inhibitors Increases Major Adverse Cardiovascular Events in Patients With Coronary Artery Disease: A Meta-Analysis. Journal of Cardiovascular Pharmacology and Therapeutics 22(2): 142-152, 2017

460 Effects of Proton-Pump Inhibitors in Patients Receiving Clopidogrel-Based Antithrombotic Therapy for Cardiovascular Prevention: A Systematic Review and Meta-Analysis of Randomized Trials. Gastroenterology 156(6): S-97, 2019

Systematic review with meta-analysis: risk of adverse cardiovascular events with proton pump inhibitors independent of clopidogrel. Alimentary Pharmacology and Therapeutics 48(8): 780-796, 2018

Effects of proton pump inhibitors in patients receiving clopidogrel: meta-analysis versus clinical practice. Drug Safety 34(2): 173; Author Reply 174, 2011

T1078 Risk of Adverse Cardiovascular Events With Concomitant use of Clopidogrel and Proton Pump Inhibitors(Ppi): Systematic Review and Meta-Analysis of Observational Studies. Gastroenterology 138(5): S-483, 2010

T1149 Risk of Upper Gastrointestinal Bleeding in Clopidogrel and Aspirin Users Receiving Concomitant Proton Pump Inhibitors. Gastroenterology 138(5): S-499, 2010

Influence of proton pump inhibitors on clinical outcomes in coronary heart disease patients receiving aspirin and clopidogrel: A meta-analysis. Medicine 97(3): E9638, 2018

The effects of proton pump inhibition on patient-reported severity of dyspepsia when receiving dual anti-platelet therapy with clopidogrel and low-dose aspirin: analysis from the Clopidogrel and the Optimization of Gastrointestinal Events Trial. Alimentary Pharmacology and Therapeutics 42(3): 365-374, 2015

Adverse cardiovascular effects of concomitant use of proton pump inhibitors and clopidogrel in patients with coronary artery disease: a systematic review and meta-analysis. Archives of Medical Research 43(3): 212-224, 2012

The prophylactic use of a proton pump inhibitor (PPI) in patients treated with clopidogrel and aspirin for an acute coronary syndrome or placement of a coronary stent reduces the rate of upper gastrointestinal bleeding with no apparent increase in cardiovascular events. Internal and Emergency Medicine 6(2): 159-160, 2011

No consistent evidence of differential cardiovascular risk amongst proton-pump inhibitors when used with clopidogrel: meta-analysis. International Journal of Cardiology 167(3): 965-974, 2013