Concomitant use of clopidogrel and proton pump inhibitors: impact on platelet function and clinical outcome- a systematic review

  title={Concomitant use of clopidogrel and proton pump inhibitors: impact on platelet function and clinical outcome- a systematic review},
  author={Jeroen Jaspers Focks and Marc A. Brouwer and Martijn G.H. van Oijen and {\'A}ngel Lanas and Deepak L. Bhatt and Freek W.A. Verheugt},
  pages={520 - 527}
Background Clopidogrel as an adjunct to aspirin has improved outcomes after acute coronary syndromes, but laboratory studies suggest a reduced antiplatelet effect when proton pump inhibitors (PPIs) are co-administered. Despite corroborating data from retrospective studies, new clinical data fuel the controversy on this issue. Purpose Systematic review of the impact of the addition of PPIs to clopidogrel on platelet function and cardiovascular outcome. Data sources PubMed, Web-of-Science… 

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

The results of the meta-analysis suggest that PPIs are a marker of increased cardiovascular risk in patients taking clopidogrel, rather than a direct cause of worse outcomes, and PPIs have the potential to decrease gastrointestinal bleeding in clopIDogrel users.

Proton Pump Inhibitors and Potential Interactions with Clopidogrel: An Update

  • L. Gerson
  • Medicine, Biology
    Current Gastroenterology Reports
  • 2013
Clinicians can assure their patients that combination therapy is safe when indicated in a patient at high risk of GI bleeding, but they should also stop PPI therapy if it is not clinically indicated.

Proton Pump Inhibitors, Platelet Reactivity, and Cardiovascular Outcomes After Drug-Eluting Stents in Clopidogrel-Treated Patients: The ADAPT-DES Study

In patients treated with clopidogrel after successful drug-eluting stents implantation, the concomitant administration of PPI was associated with high platelet reactivity and a greater rate of adverse outcomes during long-term follow-up.

Clopidogrel-Proton Pump Inhibitor Drug-Drug Interaction and Risk of Adverse Clinical Outcomes Among PCI-Treated ACS Patients: A Meta-analysis.

Concomitant clopidogrel-PPI therapy following PCI appears to be significantly associated with adverse cardiovascular events, and research on the effect of individual PPIs is needed.

Systematic review and meta-analysis of adverse cardiovascular events associated with proton pump inhibitors used alone or in combination with antiplatelet agents

Findings do not consistently support an association between MACE and PPIs when taken alone, or concomitantly with antiplatelets.

Should proton pump inhibitors be withheld from patients taking clopidogrel? The issue that has been giving me heartburn!

  • P. Berger
  • Biology
    Circulation. Cardiovascular quality and outcomes
  • 2015
A talented group of investigators from Duke would study the quality of the evidence supporting the existence of a clinically relevant interaction between PPIs and clopidogrel, finding that all randomized trials suggest that no clinically detectable interaction exists, but that most observational studies suggest that an interaction does exist.

Clopidogrel efficacy with concomitant drug therapy in patients undergoing percutaneous coronary intervention

Concomitant use of clopidogrel with PPIs, statin, or combinations of PPIs with CCBs and statins, or a combination of two drugs is associated with a higher risk of MACEs, which suggests that these medications may attenuate the antiplatelet effect clopIDogrel.

Revisiting the Clopidogrel-Proton Pump Inhibitor Interaction: From Bench to Bedside.

Gastroprotection with PPIs in patients requiring DAPT at high risk for bleeding events is supported by consensus guidelines, andeterogeneity exists in the inhibitory effects of specific PPIs on CYP2C19 isozymes.

Proton Pump Inhibitors in Cardiovascular Disease: Drug Interactions with Antiplatelet Drugs.

  • M. WürtzE. Grove
  • Biology, Medicine
    Advances in experimental medicine and biology
  • 2017
The present book chapter summarizes the evidence regarding the widespread use of platelet inhibitors and PPIs in combination, and outlines current evidence supporting or opposing drug interactions between these drugs and discusses clinical implications.



Proton pump inhibitors in patients treated with aspirin and clopidogrel after acute coronary syndrome.

  • A. GasparSílvia Ribeiro Adelino Correia
  • Medicine, Biology
    Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology
  • 2010
PPI precription in addition to aspirin and clopidogrel after ACS was not associated with a worse six-month prognosis, and independent and positive predictors of PPI prescription were older age and lower hemoglobin concentration on admission.

Safety of clopidogrel and proton pump inhibitors in patients undergoing drug-eluting stent implantation

The association of clopidogrel and PPIs after drug-eluting stent implantation, prescribed on clinical judgement, seems safe, and 1-year rates of all cause death, ST, and Thrombolysis in MI major and minor bleedings did not significantly differ.

Effect of individual proton pump inhibitors on cardiovascular events in patients treated with clopidogrel following coronary stenting:

  • H. AiharaA. Sato K. Aonuma
  • Medicine, Biology
    Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions
  • 2012
No significant association between PPI use and primary endpoint was observed in the Japanese population, whereas P PI use resulted in a significant reduction in the rate of gastrointestinal bleeding.

Risk of Adverse Clinical Outcomes with Concomitant Use of Clopidogrel and Proton Pump Inhibitors Following Percutaneous Coronary Intervention

Concomitant use of clopidogrel and PPI in post-PCI patients is associated with a higher risk of MACE, which suggests that PPIs may attenuate clopIDogrel’s beneficial antiplatelet effect, which is crucial after PCI.

Cardiovascular outcomes associated with concomitant use of clopidogrel and proton pump inhibitors in patients with acute coronary syndrome in Taiwan.

No statistically significant increase in the risk of rehospitalization for acute coronary syndrome due to concurrent use of clopidogrel and PPIs overall is indicated in an Asian population with higher prevalence of CYP2C19 intermediate and poor metabolizers.

Impact of concomitant treatment with proton pump inhibitors and clopidogrel on clinical outcome in patients after coronary stent implantation.

The data suggest that a combined use of clopidogrel as part of dual antiplatelet therapy (DAPT) after coronary stenting and PPIs does not significantly influence the clinical outcome.

Association of Proton Pump Inhibitor Use on Cardiovascular Outcomes With Clopidogrel and Ticagrelor: Insights From the Platelet Inhibition and Patient Outcomes Trial

The use of a PPI was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel, and a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment.