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OMEPRAZOLE AND CLOPIDOGREL INTERACTION: CURRENT RECOMMENDATIONS

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OMEPRAZOLE AND CLOPIDOGREL INTERACTION: CURRENT RECOMMENDATIONS

  1. 1. OMEPRAZOLE AND CLOPIDOGREL: CURRENT RECOMMENDATIONS Dr. Antonio C. Comia
  2. 2. INTRODUCTON • PROTON PUMP INHIBITORS – Has been available since the 1980’s – Inhibits the parietal cell’s proton pump – Most potent suppressor of gastric acid secretion • CLOPIDOGREL – Antiplatelet agent, thienopyridine class – Indicated for: recent stroke, MI, ACS, PAD, AF, post-PTA, peripheral artery bypass surgery
  3. 3. CLOPIDOGREL AND ASPIRIN • Individually, are used in reducing the combined risk of CV events, ischemic stroke, MI, and vascular death • In combination, significantly reduces risk of stroke, MI and death in patients with Acute Coronary Syndrome • BUT: increases risk of severe gastrointestinal bleeding
  4. 4. Case • 58 year old male came in for loss of appetite and generalized debility which started a few days prior to consult. • He is a known hypertensive and diabetic for ten years now on metformin, sitagliptin, atorvastatin, aspirin and telmisartan. • On consult noted to be hypotensive, tachycardic with irregular rhythm, in mild respiratory distress and afebrile
  5. 5. Case • He was then admitted to the ICU and subsequently managed as Sepsis secondary to Community acquired pneumonia, DM2. • During his ICU stay he developed AMI and immediately underwent angioplasty • Subsequent hospital stay was uneventful and patient was disharged.
  6. 6. Question 1 • Will you give antiplatelets: – ASA alone – Clopidogrel alone – Give combination ASA and Clopidogrel • Will you give anti-coagulants?
  7. 7. Recommendation • Dual antiplatelet therapy with aspirin and clopidogrel is recommended treatment for percutaneous coronary intervention (PCI) and acute coronary syndromes (ACS) Smith SC Jr. et al. ACC/AHA/SCAI 2005 guideline, J Am Coll Cardiol 2006 Anderson JL, Adams CD, Antman EM, et al., J Am Coll Cardiol 2007 Antman EM, Anbe DT, Armstrong PW, et al, J Am Coll Cardiol 2004
  8. 8. Question 2 • Would you give anything to prevent drug- induced gastropathy and gastrointestinal bleeding? • What will you give: – PPI – Rebamipide – H2 blockers – Antacids
  9. 9. ASA and Bleeding • Topical injury to the mucosa and systemic effects induced by prostaglandin depletion • Low-dose prophylaxis is associated with 2-4 fold increase in UGI events • Recommendation – a gastroprotective therapy should be prescribed for at-risk patients. • PPIs are the preferred agents for the therapy and prophylaxis ASA associated GI injury ACC/ACG/AHA consensus document 2008
  10. 10. Clopidogrel and bleeding • Main mechanism of action is impaired angiogenesis • Anti-angiogenic effects may impair healing of gastric erosions or small ulcerations that develop because of other meds or H. pylori leading to bleeding ACC/ACG/AHA consensus document 2008
  11. 11. Combined ASA and anticoagulant recommendation • Combination is associated with significantly increased risk of major extracranial bleeding, a large proportion in the GIT • Should be used only in established vascular, arrhythmic or valvular indication • Patients should receive concomitant PPIs as well ACC/ACG/AHA consensus document 2008
  12. 12. GI BLEEDING • GI bleeding increased mortality rate from 8% and up to 16% of patients with AMI (Nikolsky et al, 2009) • Omeprazole reduced upper GI bleeding induced by aspirin-clopidogrel combination by 87% compared with placebo (Bhatt, et al, 2010)
  13. 13. HIGH RISK 1. history of a previously complicated ulcer 2. multiple (>2) risk factors MODERATE RISK (1-2 risk factors) 1. age > 65 years 2. high dose NSAID therapy 3. previous history of uncomplicated ulcer 4. concurrent use of aspirin (inc. low dose), corticosteroids or anticoagulants Patients at increased risk for NSAID GI toxicity LOW RISK 1. no risk factors H.pylori is an independent risk factor and needs to be addressed separately Lanza, etal,Am J Gastroenterol 2009
  14. 14. H. Pylori Treatment Regimen • Primary Treatment of H. pylori Infection: – a PPI, clarithromycin, and amoxicillin, or metronidazole (clarithromycin-based triple therapy) for 14 days – a PPI or H2RA, bismuth, metronidazole, and tetracycline (bismuth quadruple therapy) for 10–14 days. ACG guidelines on H. pylori therapy 2007
  15. 15. Question #3 • Which PPI will you give? – Omeprazole – Esomeprazole – Lansoprazole – Dexlansoprazole – Rabeprazole – Pantoprazole
  16. 16. The U.S. Food and Drug Administration (FDA) has new data showing that omeprazole (Prilosec/Prilosec OTC)—a medicine used to reduce stomach acid—reduces the anti-blood clotting effect of clopidogrel (Plavix) by almost half when these two medicines are taken by the same patient. Patients at risk for heart attacks or strokes who use clopidogrel to prevent blood clots will not get the full effect of this medicine if they are also taking omeprazole. This effect is called a drug interaction and it occurs because omeprazole blocks the conversion of clopidogrel into its active form. FDA Advisory November 17, 2009
  17. 17. Rationale for Potential Interaction • Clopidogrel is metabolized by Cytochrome P450 to its active metabolite • PPIs competitively inhibits Cytochrome P540 • All PPI have demonstrated ability to decrease peak plasma concentrations of clopidogrel active metabolite and subsequent platelet aggregation (Frelinger et al,2012)
  18. 18. Clopidogrel and PPI • A diminished pharmacodynamic effect of clopidogrel has been demonstrated in patients treated with PPIs but whether its clinical efficacy is reduced remains highly controversial Gurbel, et al, Nat Rev Cardiol 2011 Sinai Center for Thrombosis
  19. 19. Pharmacodynamic Studies VS. Clinical Studies • Does PPI co-administration lead to increased rates of clinical adverse events? – Myocardial infarction – Stent occlusion – Stroke – Death
  20. 20. • Advanced age; concomitant use of warfarin, steroids, or NSAIDs; or H. pylori infection all raise the risk of GI bleeding with antiplatelet therapy. • Patients with ACS and prior upper GI bleeding are at substantial CV risk, so dual antiplatelet therapy with concomitant use of a PPI may provide the optimal balance of risk and benefit 2010 Consensus statements AHA/ACG/ACCF
  21. 21. • In the absence of large-scale, randomized, experimental studies that directly compare PPIs with different pharmacokinetic properties, the evidence remains weak for diminished antiplatelet activity associated with PPIs and thienopyridine co-prescription. 2010 Consensus statements AHA/ACG/ACCF
  22. 22. Recent Meta-analyses • Kwok, et al (2010) – 23 studies (93,278 patients) – They did not find an associated risk of PPI usage with cardiovascular events. • Kwok, et al(2012) – Updated meta-analysis of studies from 2009-2011 (23 studies with 222,311 patients) – Compares the risk of CV events of different PPIs
  23. 23. Recent Meta-analyses • Kwok, et al (2012) – There WAS an increase in CV events when PPI was given with clopidogrel. – The risk was also elevated when PPI was used alone (without clopidogrel). – There are no significant difference in risk when comparing individual PPIs.
  24. 24. Recent Meta-analyses • Kwok et al (2012) • Conclusions: – Results did not support clinically important interaction between Clopidogrel and PPIs. – The presence of confounding factors was responsible for the reason that PPI therapy without Clopidogrel was also associated with increased cardiovascular events.
  25. 25. SUMMARY OR RECENT EVIDENCE • The interaction between PPIs and clopidogrel does not appear to be clinically significant for the majority of patients. • PPI users on clopidogrel are generally older with greater co-morbidity indices, which in itself has ha higher risk of cardiovascular events. • There are no significant differences in risks between different PPIs.
  26. 26. RECOMMENDATIONS • Clinicians can comfortably prescribe PPI + clopidogrel to patients at high risk for gastrointestinal bleeding in whom combination therapy is warranted. • As the absolute risk of bleeding with a single antiplatelet agent is low, gastroprotection is not usually recommended in the absence of other risk factors.
  27. 27. THANK YOU!

Editor's Notes

  • Can we attempt to differentiate the different PPIs and POSSIBLY find an advantage for Omeprazole? Kung meron lang
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