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Effect of Proton-Pump Inhibitors On Anti-Platelet Therapy Post PCI

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Anti-platelet therapy following Percutaneous Coronary Intervention (abbreviated as PCI) is affected by the use of proton-pump inhibitors, as their activation is hindered by the latter. This article provides a detailed analysis of the mechanism by which this occurs and it's outcome.

Anti-platelet drugs:

  • An antiplatelet drug, also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. They are effective in the arterial circulation where anticoagulants have little effect.
  • Aspirin is an antiplatelet drug that may be used.
  • P2Y12 receptor blockers are another group of antiplatelet drugs. This group of drugs includes: clopidogrel, ticlopidine, ticagrelor, prasugrel, and cangrelor.

Proton pump inhibitors:

The introduction of proton-pump inhibitors (PPIs) into clinical practice since about thirty years has greatly improved our therapeutic approach to acid-related diseases for their well recognized efficacy and safety.

The main indications for PPI use are :

  1. treatment of gastroesophageal reflux disease in its various forms and complications,
  2. eradication of H. pylori infection in combination with two or more antibiotics,
  3. therapy of H. pylori-negative peptic ulcers,
  4. healing and prevention of NSAID-associated gastric ulcers
  5. co-therapy with endoscopic procedures to control upper digestive bleeding and
  6. medical treatment of Zollinger-Ellison Syndrome.


  • For several decades, coronary artery bypass grafting has been regarded as the standard choice of revascularization for significant left main coronary artery (LMCA) disease. However, in conjunction with remarkable advancement of device technology and adjunctive pharmacology, percutaneous coronary intervention (PCI) offers a more expeditious approach with rapid recovery and is a safe and effective alternative.
  • Coronary artery disease is a leading cause of morbidity and mortality in the United States and across the world. The economic impact of coronary artery disease is staggering and on the rise.
  • Percutaneous transluminal coronary angioplasty is widely used to treat severe, symptomatic coronary stenosis.
  • The Achilles heel of angioplasty is restenosis of those treated arteries. As a result, numerous therapies, including mechanical and pharmacological approaches, to prevent restenosis have been studied.


Anti-coagulant therapy post PCI:

  • After PCI, patients are prescribed double anti-platelet therapy (aspirin and a P2Y12 inhibitor) to prevent instent thrombosis.
  • Triple therapy is required in some patients, with an additional anticoagulant such as warfarin or NOAC prescribed.
  • The use of double anti-platelet therapy post PCI was associated with less bleeding than triple therapy, without increasing the risk of thromboembolic events.

Drug interactions between Proton pump inhibitors and anti- coagulants:

Data from pharmacokinetic and pharmacodynamic studies indicate that the adverse clopidogrel – proton pump inhibitor (PPI) interaction may vary between PPIs.

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One concern with using proton pump inhibitors (PPIs) is the potential interaction with the clopidogrel's antiplatelet effect, a prodrug requiring activation by cytochrome P450 isoenzymes. PPIs are competitive inhibitors of cytochrome P450. Moreover, individual PPIs have different effects on CYP metabolism and thus may adversely affect clopidogrel metabolism and subsequent cardiovascular (CV) outcomes to varying degrees.


  • The post-PCI patients on dual antiplatelet therapy with clopidogrel in the PPI group were associated with higher risk of MACE (Major Adverse Cardiovascular Events) and MI (Myocardial infarction)
  • Although the results for rabeprazole were not robust, it was the only PPI that did not yield a significantly increased risk of MACE.As with previous studies, concomitantly administered PPIs with clopidogrel had a protective effect on GI bleeding.
  • the use of low-dose PPIs did not lead to an increased risk of MACE with a sustaining protective effect against GI bleeding (the PPIs used in those studies were rabeprazole 10 mg, esomeprazole 20 mg, and omeprazole 10 mg). Therefore, low-dose PPIs can be an option for clinicians who are simultaneously concerned about the risk of clopidogrel–PPI interaction and the need to prevent GI bleeding.


  • There is evidence for a significant association between the risk of MACE and PPI use as a class effect in post-PCI patients on DAPT. Dual antiplatelet therapy
  • The risk of myocardial infarction in patients receiving any PPI was higher compared to those without PPI.

The risk of GI bleeding (a consequence of anti-coagulant therapy) was also lower with PPI co-therapy than that in the histamine 2 receptor antagonist treatment groups (Other potential treatments for gastric ailm


1] Influence of individual proton pump inhibitors on clinical outcomes in patients receiving clopidogrel following percutaneous coronary intervention

2021, Medicine (United States

2]Review article

Overview of therapies for prevention of restenosis after coronary interventions

Pharmacology & TherapeuticsNovember–December 2001...

  1. Samer M Garas
  2. Philip Huber
  3. Neal A Scott

This content is for informational purposes only and does not substitute for formal and individualized diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed medical professional. Do not stop or alter your current course of treatment. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.

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