1 / 17

Use of PPIs during Clopidogrel Therapy

Use of PPIs during Clopidogrel Therapy. Andrew N. Schmelz, PharmD Post-Doctoral Teaching Fellow Dept of Pharmacy Practice Purdue University February 26, 2009. Objectives. Describe the conversion of clopidogrel to its active metabolite Rank PPIs in regard to 2C19 metabolism

locke
Download Presentation

Use of PPIs during Clopidogrel Therapy

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Use of PPIs during Clopidogrel Therapy Andrew N. Schmelz, PharmD Post-Doctoral Teaching Fellow Dept of Pharmacy Practice Purdue University February 26, 2009

  2. Objectives • Describe the conversion of clopidogrel to its active metabolite • Rank PPIs in regard to 2C19 metabolism • Summarize relevant literature regarding use of clopidogrel and PPIs • Develop a recommendation in response to patient-specific scenarios involving clopidogrel and PPIs

  3. Background • Clopidogrel is a second-generation thienopyridine • Inhibits platelet aggregation by blocking the P2Y12 ADP receptor • PPIs are commonly used in clopidogrel-treated patients • Impaired healing of gastric ulcers AHA/ACCF Consensus Statement UA/NSTEMI Guidelines

  4. Clopidogrel Metabolism • Clopidogrel is a PRODRUG J Clin Pharmacol. 2008; 48; 475

  5. Clopidogrel Nonresponse • Occurrence of thrombotic events in patients treated with clopidogrel • Possible explanations: • Genetic polymorphisms • Competitive drug interactions • Noncompliance • Interpatient variability of the P2Y12 receptor • Indicated by platelet aggregation tests (VASP phosphorylation analysis)

  6. Enzyme Inhibition • PPIs inhibit CYP450 enzymes • Competitive inhibition occurs to varying degrees • Omeprazole • Pantoprazole • Lansoprazole • Rabeprazole Most 2C19 Metabolism Least 2C19 Metabolism Aliment Pharmacol Ther 1999;13(Suppl 3):27-36

  7. PPI Metabolism Aliment Pharmacol Ther 1999;13(Suppl 3):27-36

  8. Literature OCLA Study (omeprazole) • In vitro study measuring platelet reactivity index (PRI) and • PRI on Day 7 • Clopidogrel + PPI group: 39.8% (SD 5.6) • Clopidogrel + PBO group: 51.4% (SD 15.4) J Am Coll Cardiol. 2008 Jan 22;51(3):256-60.

  9. Literature (cont.) Small et al. (lansoprazole) • Lilly study; clopidogrel v. prasugrel • Clopidogrel inactive metabolite • AUC unaffected (not a good surrogate?) • IPA decreased • Prasugrel active metabolite • AUC insignificantly decreased (12%) • IPA insignificantly reduced J Clin Pharmacol. 2008; 48; 475

  10. Clopidogrel PK and PD

  11. Literature (cont.) Siller-Matula et al. (esomep & pantop) • In vitro study measuring PRI • Esomeprazole • No difference in PRI from PBO • Pantoprazole • No difference in PRI from PBO Am Heart J. 2009 Jan;157(1):148

  12. Claims Data MEDCO • Clopidogrel alone (n=9800) • Clopidogrel + PPI (n=6800) • RR major adverse cardiovascular events 50% higher in clopidogrel + PPI group • RR AMI 75% higher with PPI addition • AR for CV events in 12 months 25% Circulation, Oct 2008; 118: S_815

  13. Claims Data (cont.) • AETNA J Am Coll Cardiol, 2008; 52:1038-1039

  14. Observational Analysis of CREDO Circulation, Oct 2008; 118: S_815

  15. Questions?

  16. Patient Case • 65 YOM with documented CAD (in left main and circumflex arteries) s/p drug-eluting stent placement • PMH: DM, PUD, HTN • SH: (+) tobacco 2PPD X 10 years

  17. Recommendations • Avoid routine use of PPIs in patients receiving clopidogrel therapy • Control other risk factors for ischemic events • Counsel patients of s/sxs bleeding • Evaluate potential new therapies for CYP450 interactions

More Related