1 / 21

Optimal Clopidogrel Dosing

The antiplatelet effect of higher loading and maintenance dose regimens of clopidogrel: the Plavix Response in Coronary Intervention (PRINC) trial ACTRN12606000129583.

georgia-stanley
Download Presentation

Optimal Clopidogrel Dosing

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. The antiplatelet effect of higher loading and maintenance dose regimens of clopidogrel: the Plavix Response in Coronary Intervention (PRINC) trialACTRN12606000129583 1Gladding PA, 1Webster MW, 1Zeng I, 1Farrell H, 1Stewart J, 1Ruygrok P, 1Ormiston J, 2Gunes A, 3Perry J, Dahl M-L. 1Green Lane Cardiovascular Department 3Liggins Institute, Auckland, NZ 2Uppsala University, Sweden Funded by GLREF, NHF Support from Sanofi NZ

  2. Optimal Clopidogrel Dosing • Important for two reasons: • Antiplatelet effect at PCI corresponds with periprocedural infarction (ARMYDA-2) • Timing: Dosing <6-10hrs prior to PCI ineffective (CREDO) • Three recent studies have indicated that doses >600mg are notmore effective than 600mg

  3. Aims • To compare a higher split loading dose of clopidogrel (600mg + 600mg) with standard 600mg • Compare 150mg with 75mg once daily • Investigate the pharmacogenomics of clopidogrel

  4. Methods N=36 150mg/day Clopidogrel

  5. VerifyNow Platelet Function Analyser

  6. VerifyNow P2Y12 assay correlates well with Gold standard LTA van Werkum JW et al. J Thromb Haemost 2006;4(11):2516-8.

  7. Results of the PRINC (Plavix Response in Coronary Intervention) trial.

  8. Randomisation Effective Patients Well Matched in All Treatment Groups c.f age

  9. PRINCe study Non-responders

  10. Increase in Periprocedural MI (7hrs) in Clopidogrel Nonresponders

  11. Drug Response is Predictable Within the First Few Hours r = 0.72 p <0.0001 <2% platelet inhibition at 2 hrs predicts non-responder status at 7hrs (sensitivity 100%, specificity 88%) <2% platelet inhibition at 2 hrs predicts nonresponder status at 7hrs (sensitivity 100%, specificity 88%) r = 0.65 p <0.0001 r = 0.80 p <0.0001 r = 0.62 p <0.0001 r = 0.75 p <0.0001 r = 0.72 p <0.0001

  12. 1,200mg Split Dose of Clopidogrel is More Effective than Single LD Additional 600mg dose 1,200mg split dose n = 37 Standard 600mg dose 600mg dose n = 23 P = 0.03

  13. 150mg Clopidogrel OD has a Greater Antiplatelet Effect than 75mg OD P = 0.01 49.8% 28.8% 5.5% 3.7%

  14. Safety

  15. Clopidogrel Pharmacogenomics P2Y12 Receptor: H2 haplotype MDR1 C3435T genotype Biotransformation by CYP3A4, 3A5, C219, 2C9, 1A2 Polymorphic variants

  16. CYP2C19 Genetic Variants Influence Clopidogrel Response

  17. No benefit of higher dosing in normal *1 genotypes

  18. Loss of function carriers respond to higher doses

  19. Finding validated in higher maintenance dosing group

  20. Conclusion • Split loading with 600mg + 600mg (2hrs) clopidogrel increases the antiplatelet effect • 150mg OD > 75mg OD antiplatelet effect • Response can be measured robustly with a POC analyser & predicted early (2hrs) • Pharmacogenetics might predict response before Rx but phenotyping is still very effective

  21. Mark Webster Ralph Stewart Irene Zeng Helen Farrell Arzu Gunes M-L Dahl Jo Perry Auckland City Hospital Pharmacy Clinical Trials Unit

More Related