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Nick Curzen BM(Hons) PhD FRCP
Professor of Interventional Cardiology University Hospital Southampton
UK
Should cangrelor pretreatment be used in nearly all patients with STEMI & NSTEMI And many with stable CAD?
Definitely not- an expensive way to increase bleeding without much benefit!
Disclosure Statement of Financial Interest
• Grant/Research Support
• Consulting Fees/Honoraria
• Haemonetics; • Medtronic • St Jude Medical
• Haemonetics; • Medtronic; • St Jude Medical • Abbott Vascular; • HeartFlow; • DS/Lilly
Within the past 12 months, I have had a financial interest/ arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship Company
Background to my case
ü Cangrelor has some v attractive properties & shows great promise as a rapid onset & offset P2Y12 inhibitor…..
BUT ü There are some flaws in the current sales pitch… I cannot “buy it”! ü Current evidence does not really support its widespread use in PCI
ü In fact the current data actually support the use of clopidogrel!
ü We simply need some more data!!
Isn’t the argument all sewn up…?
Lancet 2013
Pooled analysis of CHAMPION PCI + CHAMPION PLATFORM + CHAMPION PHOENIX n= nearly 25,000 patients
Nothing in life is that simple!
Problems with cangrelor
BLEEDING Lancet 2013
Circulation 2011
This is not a little bit of bleeding!!!
Cangrelor is associated with excess bleeding cf clopidogrel
Problems with cangrelor
Problems with cangrelor
The apparent difference between cangrelor & clopidogrel is actually…
less to do with cangrelor & more to do with clopidogrel!
CHAMPION PHOENIX N Engl J Med 2013
CHAMPION PLATFORM N Engl J Med 2009
CHAMPION PCI N Engl J Med 2009
û û
Slide source: Dr T Marciniak
Relationship between time of Clopidogrel administration & endpoints
Cangrelor is not superior if clopidogrel is given early (? Before) PCI
Problems with cangrelor
PCI PLATFORM PHOENIX n 8877 5362 11145
popula0on SA+NSTEMI+STEMI SA+ NSTEMI SA+NSTEMI+STEMI
0ming of clopidogrel Within 30 mins before PCI
End of procedure Unclear… 30% aLer PCI
Death (%) 0.1 0.7 0.3
ST (%) 0.3 0.6 1.4
ST difference vs cangrelor?
0.34
0.02
0.01
Effect of Clopidogrel preloading on outcomes in comparator groups
PCI PLATFORM PHOENIX n 8877 5362 11145
popula0on SA+NSTEMI+STEMI SA+ NSTEMI SA+NSTEMI+STEMI
0ming of clopidogrel Within 30 mins before PCI
End of procedure Unclear… 30% aIer PCI
Death (%) 0.1 0.7 0.3
ST (%) 0.3 0.6 1.4
ST difference vs cangrelor?
0.34
0.02
0.01
Effect of Clopidogrel preloading on outcomes in comparator groups
PCI PLATFORM PHOENIX n 8877 5362 11145
popula0on SA+NSTEMI+STEMI SA+ NSTEMI SA+NSTEMI+STEMI
0ming of clopidogrel Within 30 mins before PCI
End of procedure Unclear… 30% aLer PCI
Death (%) 0.1 0.7 0.3
ST (%) 0.3 0.6 1.4
ST difference vs cangrelor?
0.34
0.02
0.01
Effect of Clopidogrel preloading on outcomes in comparator groups
PCI PLATFORM PHOENIX n 8877 5362 11145
popula0on SA+NSTEMI+STEMI SA+ NSTEMI SA+NSTEMI+STEMI
0ming of clopidogrel Within 30 mins before PCI
End of procedure Unclear… 30% aLer PCI
Death (%) 0.1 0.7 0.3
ST (%) 0.3 0.6 1.4
ST difference vs cangrelor?
0.34
0.02
0.01
Effect of Clopidogrel preloading on outcomes in comparator groups
Early/pre-PCI clopidogrel is highly effective at reducing
events in mixed PCI population
Problems with cangrelor
Problems with cangrelor
Is it actually better in STEMI/PPCI? …. The group you might expect it to be MOST effective in cf oral P2Y12 inhibitor
STEMI
Problems with cangrelor
Is it actually better in STEMI/PPCI? …. The group you might expect it to be MOST effective in cf oral P2Y12 inhibitor
STEMI
Problems with cangrelor
Is it actually better in STEMI/PPCI? …. The group you might expect it to be MOST effective in cf oral P2Y12 inhibitor
STEMI
û
Cangrelor is not superior to clopidogrel in STEMI in the CHAMPION trials
Problems with cangrelor
SUMMARY
ü Cangrelor is an exciting agent allowing on/off transient P2Y12 receptor inhibition
ü Some data suggest that cangrelor reduces ischaemic events in some PCI patients cf Clopidogrel but it is noisy given heterogeneous populations & treatment timing …
ü When clopidogrel is given before PCI in a heterogeneous PCI population, there is no clinical endpoint advantage from cangrelor…
ü The CHAMPION trial series has evolved from giving clopi pre-PCI to post (? Why?)…
ü The CHAMPION trial series show clear outome advantage of pre-PCI clopidogrel
ü The current data deny any benefit for cangrelor in STEMI… despite intuitive predictions!
ü Cangrelor is associated with increased bleeding cf clopidogrel
ü Generic clopidogrel is very cheap & cangrelor is very expensive
ü We cannot possibly justify cangrelor for most PCI patients based upon current data!
ü We need randomised trials of single & discrete patient groups cf pre-loaded clopidogrel
CONCLUSION