definitely not- an expensive way to increase bleeding ... · • st jude medical ... there are some...

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