1. Antiplatelet Therapy For STEMI: The Case for Cangrelor
Gary L. Schaer, MD FACC, FAHA, FSCAI
Professor of Medicine (Interventional Cardiology)
Director, Cardiology Research
Rush University Medical Center
Chicago IL

2. Gary L. Schaer MD Consultant; Advisory Board The Medicines Company
Disclosure Statement of Financial Interest
Consultant; Advisory Board
The Medicines Company
AstraZeneca

3. Cangrelor Pharmacology
FDA approved 6/2015
Indication: as an adjunct to PCI for reducing the risk of periprocedural MI, repeat coronary revascularization, and stent thrombosis in patients not treated with a P2Y12 inhibitor or GP IIb/IIIa inhibitor
Immediate onset: IV, direct-acting
Consistent effect: Not influenced by age, gender, renal function, or genetic variations
Rapid offset: Reversible; half-life of 3-6 min; clearance independent of organ function; return of platelet function within 1h

4. Cangrelor Pharmacokinetic and Pharmacodynamic Profile

5. Transition to Oral P2Y12 Inhibitors

6. Champion Phoenix
Pivotal Phase 3 trial of 11,145 patients undergoing urgent or elective PCI
Randomized (1:1), double blind, double dummy trial
Comparator: clopidogrel ( mg) according to standard of care
Key inclusion: Stable angina, NSTE-ACS or STEMI
Key exclusion:
Treatment with P2Y12 inhibitor within 7 days
Using or plan to use a GPIIb/IIIa inhibitor
Primary efficacy endpoint: 48h composite (death, MI, ischemia-driven revascularization, stent thrombosis)
Primary safety endpoint: severe bleeding at 48h
Bhatt DL et al. NEJM 2013: 368;1303

7. C-Phoenix – Study Design
2/3 rec’d clopdigorel at the start of PCI, 1/3 at the end of PCI. Median duration of PCI was 22 min.
Infusion of cangrelor was for at least 2 hours but could be given up to 4 hours. Median duration of infusion was 122 min.
Clopidogrel dose** - patients – 4064 (73%) received 600 mg – 1427 (26%) received 300 mg
• Clopidogrel dose* - sites – 6 sites dosed only 300 mg – 118 sites dosed only 600 mg – 27 sites dosed both
United States: 99% of patients received 600 mg
Clopidogrel timing***
– 3442 (62%) before start of PCI – Median time: -5 minutes
– 1997 (36%) after start of PCI – Median time: 20 minutes

8. C-Phoenix: Baseline Characteristics

9. C-Phoenix: Primary Efficacy Endpoint (Death, MI, IDR, or ST at 48h)
Event Rate (%)
OR 0.78 (95% CI, ); P = (Prespecified logistic-regression analysis)
(0.8% vs. 1.4%; odds ratio, 0.62; 95% CI, 0.43 to 0.90; P = 0.01)
Intraprocedural stent thrombosis: lower in cangrelor group (0.6% vs. 1.0%; odds ratio, 0.65; 95% CI, 0.42 to 0.99; P = 0.04).
Use of bailout GPIIb/IIIa inhibitor was 2.3% vs. 3.5%. OR 0.65; 95% CI, 0.52 to 0.82; P<0.001)
Hours Since Randomization 2h
Bhatt DL et al. NEJM 2013: 368;1303

10. C-Phoenix: Stent Thrombosis (Key Secondary Endpoint, ARC def)
Event Rate (%)
OR 0.62 (95% CI, ); P = 0.01
(0.8% vs. 1.4%; odds ratio, 0.62; 95% CI, 0.43 to 0.90; P = 0.01)
Intraprocedural stent thrombosis: lower in cangrelor group (0.6% vs. 1.0%; odds ratio, 0.65; 95% CI, 0.42 to 0.99; P = 0.04).
Use of bailout GPIIb/IIIa inhibitor was 2.3% vs. 3.5%. OR 0.65; 95% CI, 0.52 to 0.82; P<0.001)
Hours Since Randomization 2h
Bhatt DL et al. NEJM 2013: 368;1303

11. C-Phoenix: Bleeding Events
End Point
Cangrelor (5529)
Clopidogrel (5527)
Odds Ratio (95% CI)
P Value
GUSTO defined bleeding
Primary safety endpoint
(severe or life threatening)
9 (0.2%)
6 (0.1%)
1.6 ( )
0.44
Moderate bleeding
22 (0.4%)
13 (0.2%)
1.69 ( )
0.13
Severe or moderate
31 (0.6%)
19 (0.3%)
1.63 ( )
0.09
Any blood transfusion
25 (0.5%)
16 (0.3%)
1.56 ( )
0.16
Efficacy and safety: net adverse clinical events
Death, MI, IDR, ST or GUSTO severe bleeding
264 (4.8%)
327 (6%)
0.80 ( )
0.008
SAY SOMETHING ABOUT OTHER SAFETY ISSUES – 1% OVERALL INCIDENCE OF DYSPNEA DURING THE INFUSION – MOST OF IT MILD.
Bhatt DL et al. NEJM 2013: 368;1303

12. C-Phoenix: Outcome by Clinical Presentation
SAY SOMETHING ABOUT OTHER SAFETY ISSUES – 1% OVERALL INCIDENCE OF DYSPNEA DURING THE INFUSION – MOST OF IT MILD.
Bhatt DL et al. NEJM 2013: 368;1303

13. Efficacy Outcomes at 48h by Treatment Group and Clinical Presentation (mITT Population)
SAY SOMETHING ABOUT OTHER SAFETY ISSUES – 1% OVERALL INCIDENCE OF DYSPNEA DURING THE INFUSION – MOST OF IT MILD.
Abtan J et al. JACC Intv 2016:9;1905

14. Cost Cangrelor vials contain 50 mg at $749
Dose: 30mcg/kg bolus x 4mcg/kg/min x 120 min
Up to 100 kg = 1 $749
>100 kg = 2 $1,498
>200 kg = 3 $2,100

15. EKG ACS Management Pathway STEMI Pathway NSTE-ACS Pathway
Patient presents with symptoms of ACS
EKG
No ST-elevation
ST-elevation
ACS Management
Pathway
NSTE-ACS Pathway
Aspirin 325 mg po or chewed + UFH (not LMWH)
DO NOT GIVE TICAGRELOR OR CLOPIDOGREL BEFORE CORONARY ANGIOGRAPHY
STEMI Pathway
Aspirin 325 mg po or chewed
Emergency transfer to cath lab
DO NOT GIVE TICAGRELOR OR CLOPIDOGREL BEFORE CORONARY ANGIOGRAPHY
Ischemia-Guided Strategy (low risk)
Low risk TIMI score (0-1), GRACE (<109)
Low risk trop neg female patients
Patient or clinician preference in absence of high-risk features
Stress test (if + => Cath)
Early Invasive Strategy (intermediate to high risk)
DO NOT GIVE TICAGRELOR OR CLOPIDOGREL BEFORE CORONARY ANGIOGRAPHY
Unfractionated heparin and anti-ischemic therapy
Immediate Invasive Cath <2h
Refractory or recurrent angina despite Med Rx
Severe HF, unstable hemodynamics, malignant arrhythmias
Early Invasive
Cath <24h
No “immediate invasive” features
GRACE score >140
Temporal change in Trop
New ST-seg depression
Delayed Invasive
Cath 25-72hs
GFR <60 mL/min/1.73m2
EF <40%
Early post-MI angina
PCI within 6mo or CABG
GRACE or TIMI >2
Coronary Angiography -> PCI
At start of PCI consider cangrelor (bolus + 2hr infusion) + anticoagulant (bivalirudin or UFH)
Transition to oral P2Y12 therapy (if surgery not planned prior to discharge): ticagrelor 180 (begin during cangrelor infusion), or clopidogrel 600 mg (must begin immediately after cangrelor d/c).

16. CANGRELOR FOR STEMI Cost $$$$ Advantages Disadvantages 20%  MI @ 48h
62%  stent thrombosis
 Pre-load oral P2Y12 
 delay if CABG needed
Cost
$$$$
Reduces need for provisional GPIIbIIIa
Excellent safety profile
Advantages
Disadvantages