La terapia antiaggregante endovenosa nel paziente STEMI

candidato a PCI primaria PRO Cangrelor

Sergio Leonardi, MD, MHS, FESC

Gardone Riviera, 16 Aprile 2016

Cangrelor. Now Approved

23 March 2015: Kengrexal approved for the EU by EMA 22 June 2015: The FDA approved Kengreal

References 158-161: CHAMPION PCI, PLATFORM, PHOENIX, Lancet Meta-analysis.

Cangrelor and GPI in CHAMPION

J Am Coll Cardiol 2016;67(13_S):452-452.

PHOENIX GPI use

Bhatt DL. N Engl J Med 2013;368:1303-13.

380 of 10,942 patients (modified ITT population) received GPI (3.5%)

Cangrelor N=5472

Clopidogrel N=5470

OR (95% CI) P-value

Bailout*

129 (2.3%) 194 (3.8%) 0.65 (0.52, 0.82) <0.001

*GPI allowed as bailout during PCI to treat new or persistent thrombus, slow flow or no reflow, side branch compromise, dissection, or distal embolization

148 of 2770 patients received GPI (5.3%)

Pre-Treatment N=1394

No Pre-Treatment N=1376

HR (95% CI) p Value

Bailout

72 (5.2%) 76 (5.5%) 0.94 (0.68,1.30) 0.70

ACCOAST GPI use

Montalescot JACC 2014

Variable Adjusted OR [95%CI] P value

STEMI (vs. stable angina) 1.87 [1.04,3.36] 0.04

NSTE-ACS (vs. stable angina) 2.07 [1.26,3.40] 0.004

Thrombus at baseline 1.79 [1.12,2.84] 0.01

Total stent length (per 1 mm ↑) 1.03 [1.02,1.03] <0.0001

Cangrelor (vs. clopidogrel) 0.65 [0.42,1.00] 0.048

Independent predictors of IPST

* Other variables in the model: Current smoker, number of PCI vessels, DES vs. BMS, TIMI flow at baseline, US vs. non-US site

IPST in CHAMPION PHOENIX 10,939 pts assessed by a blinded core lab

Généreux P et al. JACC 014;63:619–29

0

1

2

3

4

5

6

0 1 2

2 Hour Landmark Analysis First Occurrence of Death/MI/IDR/ST Within 48 Hours

0 6 12 18 24 30 36 42 48

Esti

mat

e Ev

ent

Rat

e (%

)

Hours from Randomization

Cangrelor: 5472 5265 5249 5233 5229 5225 5223 5221 5220 5217 5212

Clopidogrel: 5470 5214 5177 5162 5159 5155 5152 5151 5151 5147 5146

Patients at risk:

Cangrelor

Clopidogrel

End of cangrelor infusion

600 mg clopidogrel given Or matching placebo

5.4%

4.1%

HR (95% CI): 0.76 (0.64, 0.90)

p=0.002

0.7% 0.6%

HR (95% CI): 1.16 (0.70, 1.90)

p=0.57

Cavender M et al. Eur Heart J. 2014;35 (Abstract Suppl):136

Kinetics of Platelet Inhibition Over Time in STEMI

0

50

100

150

200

250

300

350

400

Basal 2 hours 4 hours 8 hours 12 hours

Prasugrel

Ticagrelor

Pla

tele

t R

eact

ivit

y U

nit

s †

†

‡

‡

*

Parodi G. et al. J Am Coll Cardiol. 2013;61(15):1601-06.

Residual platelet reactivity values assessed by platelet reactivity units (PRU) VerifyNow at baseline and 2, 4, 8, and 12 h after drug loading dose in patients with prasugrel (triangles) and ticagrelor (squares). *p < 0.01 versus Ticagrelor. †p < 0.01 versus baseline, ‡p < 0.01 versus 2 h.

Conclusions

• If immediate platelet inhibition is clinically indicated, consider a step-wise approach: cangrelor GPI as bailout

• Cangrelor is immediately reversible, GPIs are not.

• (Cangrelor data in STEMI patients are limited).