Cangrelor Not the CHAMPION We Hoped For James Coons PharmD FCCP FACC BCCP UPMC Presbyterian Hospital University of Pittsburgh Disclosures Nothing to disclose CHAMPION Trials Experience Study ID: 1001228
Download Presentation The PPT/PDF document "Cangrelor : Friend or Foe? -" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
1. Cangrelor: Friend or Foe? - Cangrelor: Not the CHAMPION We Hoped ForJames Coons, PharmD, FCCP, FACC, BCCPUPMC Presbyterian HospitalUniversity of Pittsburgh
2. DisclosuresNothing to disclose
3. CHAMPION Trials ExperienceStudyPatient PopulationComparatorOutcomes (cangrelor vs. clopidogrel)CHAMPION- PCI (2009)n=8,66774% NSTE-ACS15% stable angina11% STEMIClopidogrel 600 mg at start of PCIAll-cause death/MI/revasc: 7.5% vs. 7.1%; p=0.59Bleeds: ACUITY minor/GUSTO mild sig. ↑ w/ cangrelor; no difference in major bleedsCHAMPION-PLATFORM (2009)n=5,30194% NSTE-ACS5% stable anginaClopidogrel 600 mg at end of PCIAll-cause death/MI/revasc: 7% vs. 8%; p=0.17Bleeds: ACUITY minor & major/GUSTO mild sig. ↑ w/ cangrelor; no difference in other major bleedsCHAMPION-PHOENIX (2013)n=11,14556% stable angina25% NSTE-ACS 18% STEMIClopidogrel at start or end of PCI; 600 mg (74%) or 300 mg (26%)All-cause death/MI/revasc/ST: 4.7% vs. 5.9%; p=0.005Bleeds (primary – GUSTO severe): no differenceN Engl J Med 2009;361:2318-29; N Engl J Med 2009;361:2330-41; N Engl J Med 2013;368:1303-13.
4. CHAMPION trials: LimitationsCompared to strategy of deferred P2Y12 inhibitorLow proportion STEMIData reporting (ITT, modified ITT, safety)Multiple bleeding definitions Premature study discontinuation N Engl J Med 2009;361:2318-29; N Engl J Med 2009;361:2330-41; N Engl J Med 2013;368:1303-13.
5. CHAMPION PHOENIX: Notable differencesIncluded stent thrombosis (ST) in primary compositeDifferent peri-procedural MI and ST definition/adjudicationAllowed for 300 mg LD clopidogrel (~25% of population)> 50% with stable anginaACUITY definition of bleeding and GUSTO mild not reportedN Engl J Med 2013;368:1303-13.
6. Practice Evolution Since CHAMPION trials completed (@ 2013):↑ trans-radial access↑ 2nd-generation DES↑ use of potent oral P2Y12 inhibitors ↓ use of GPIs Bleeding definition harmonization (BARC) Availability of pharmacogenomics (CYP2C19) JACC Cardiovasc Interv 2010;3:1209-19; N Engl J Med 2017;21:2053-64. J Am Coll Cardiol 2013;6:496-504. N Engl J Med 2019;381:1621-31.
7. Unanswered Questions Clinical outcomes vs. clopidogrel pre-treatmentClinical outcomes vs. ticagrelor/prasugrelSurrogate endpoints per recently completed and ongoing studiesCANTIC (platelet inhibition vs. crushed ticagrelor)Ubaid et al. and NCT03182855 (platelet reactivity/inhibition in STEMI vs. ticagrelor)Lancet 2001;358:527-33. JAMA 2002;288:2411-20. JAMA 2005;294:1224-32. Circulation 2019;139:1661-70. Thromb Haemost 2019;119:1171-81.
8. Unanswered Questions Cangrelor vs. routine GPI – similar efficacy, less bleeding with cangrelor (CHAMPION post-hoc)Direct comparison with bolus only or bolus/short-infusion GPISurrogate endpoints per ongoing studiesFABOLUS FASTER (platelet inhibition in STEMI vs. tirofiban bolus/infusion vs. prasugrel) Clinical outcomes vs. selective/bailout only GP IIb/IIIa inhibitors?JAMA Cardiol 2017;2:127-35. J Cardiovasc Trans Res 2020;doi.org/10.1007/s12265-020-09969-4.
9. GuidelinesACC/AHA – not addressedESC 2018Cangrelor may be considered peri-procedurally in patients naïve to P2Y12 inhibitors (stable CAD, NSTE-ACS, STEMI) – IIb-A recommendationEur Heart J 2016;37:267-315.
10. Summary of EvidenceAvailable evidence suggests a numerically small benefit for major ischemic endpoints that is counterbalanced by increase in relevant (but not severe) bleedingProven efficacy in preventing intra- and post-procedural stent thrombosis, particularly among patients treated with deferred oral P2Y12 inhibitorEur Heart J 2016;37:267-315.
11. Cost ConsiderationsCangrelor - ~ $900 per 50 mg vial (AWP)2 vials anticipated for patients ≥ 100 kgOral P2Y12 inhibitor LD (AWP): clopidogrel (~$56), ticagrelor (~$15), prasugrel (~$99)Intraprocedural thrombotic events and bleeding events associated with increased hospitalization costsCost-effectiveness analysis neededAnn Pharmacother 2019;53:726-37. UpToDate.com. Accessed May 8, 2020.
12. Conclusions and Place in TherapyCangrelor has a therapeutic niche for PCI, but is ‘not the CHAMPION we had hoped for’PK and PD advantages are attractive, although trials show modest benefits on outcomes vs. clopidogrel or placeboSeveral unanswered questions remain, especially in contemporary PCI setting
13. Conclusions and Place in TherapyConsider cangrelor in patients who are P2Y12 inhibitor-naïve and when PCI likelihood is highNo enteral access or inability to take an oral P2Y12 inhibitor (i.e. nausea/vomiting, cardiac arrest, shock)Pre-loading not feasible (i.e., STEMI)Am J Cardiovasc Drugs 2017;17:5-16.
14. Questionscoonsjc@upmc.edu