1. Should We Preload STEMI Patients with Antiplatelet Therapy?
CRT 2017, Washington, DC. February 2017
Should We Preload STEMI Patients with
Antiplatelet Therapy?
A. Michael Lincoff, M.D.
Director, C5Research
(Cleveland Clinic Coordinating Center for Clinical Research)
Director, Center for Clinical Research
Lerner Research Institute
Vice Chairman of Cardiovascular Medicine
Professor of Medicine
Heart and Vascular Institute

2. Speaker Disclosure – A. Michael Lincoff, MD
Relationships with Industry
Research Funding:
AstraZeneca, CSL Behring, Eli Lilly, Esperion, Pfizer, Roche
Consultant:
Abbott, Amgen, Sarepta, Sermonix, St. Jude Medical
Supervisory – C5Research Director:
Amgen, Atricure, Cardiovascular Systems, Centocor, Covidien, Edwards Lifesciences, Early Sense, Ethicon, Janssen, Juventas, Medicines Company, Medtronic, Novartis, Orexigen, Stemedica, Takeda 2

3. CURE Trial MACE – Sustained and Very Early Effect
CURE Trial Investigators. N Engl J Med. 2001;345:494
Yusuf S, et al. Circulation. 2003;107:966

4. Clopidogrel 300 mg Load Before Elective PCI
CREDO Trial
Clopidogrel 300 mg Load Before Elective PCI
Steinhubl et al. JACC 2006;47:939
Steinhubl et al. JAMA. 2002;288:2411
P = 0.23 for ITT
P = for comparison to >6 hr Pre-Rx

5. Clopidogrel Pretreatment in PCI
Meta-Analysis
No significant reduction in mortality - OR, 0.80; 95% CI, ; P= .17
Bellemain-Appaix et al. JAMA 2012;308:2507

6. Prasugrel and Ticagrelor
Pharmacodynamics of Platelet Inhibition vs Clopidogrel
Ticagrelor
Prasugrel
Gurbel et al.
Circulation 2009;120:
Wiviott et al.
Circulation 2010;122:

7. ACCOAST Trial Prasugrel Pretreatment in NSTEMI
4033 pts with NSTEMI, scheduled for coronary angio within 2-48 hrs after randomization
Pretreatment
Prasugrel 30 mg
No Pretreatment
Placebo
Median
4.4 hrs
4.2 hrs
Coronary Angiography
PCI – 69%
CABG – 6%, Medical Rx – 25%
For PCI
Prasugrel 30 mg
Prasugrel 60 mg
Ischemic and Bleeding Endpoints
7 Days
Montalescot et al. NEJM 2013;369:999.

8. ACCOAST Trial Prasugrel Pretreatment in NSTEMI
Efficacy and Bleeding in Entire Population
Montalescot et al. NEJM 2013;369:999.

9. ATLANTIC Trial Ticagrelor Pretreatment in STEMI
1862 pts with STEMI, <6 hr duration, undergoing 1o PCI
Pre-Hospital
(in ambulance)
Ticagrelor 180 mg
In-Hospital
(in cath lab)
Placebo
Median 31 minutes
between loading doses
In Cath Lab
Placebo
Ticagrelor 180 mg
Median 28 minutes from
2nd loading dose to PCI
PCI – 88%, CABG – 1%, Medical Rx – 11%
ST Resolution, TIMI flow, Ischemic and Bleeding Events 30 Days
Montalescot et al. NEJM 2014.

10. Ticagrelor Pretreatment in STEMI – Ischemic Outcome
ATLANTIC Trial
Ticagrelor Pretreatment in STEMI – Ischemic Outcome
Montalescot et al. NEJM 2014.

11. ATLANTIC Trial – Platelet Substudy
Ticagrelor Pretreatment in STEMI
Montalescot et al. NEJM 2014 – Supplemental Appendix.

12. Ticagrelor Pretreatment in STEMI – Bleeding
ATLANTIC Trial
Ticagrelor Pretreatment in STEMI – Bleeding
Montalescot et al. NEJM 2014.

13. Clopidogrel in STEMI Platelet Aggregation High Dose Clopidogrel 600 mg
Heestermans et al. Thrombosis Research (2008) 122, 776

14. Prasugrel and Ticagrelor in STEMI
Pharmacodynamics – Delayed Onset of Action
Parodi et al. JACC 2013;61:1601

15. Ticagrelor Bioavailability of Crushed Ticagrelor Tablets
Open-Label Study in Healthy Volunteers
Teng et al. Int J of Clin Pharm and Therap 2015;53:182.

16. Prasugrel and GP IIb/IIIa Inhibition
Tirofiban and Prasugrel in STEMI – FABOLUS PRO
Valgimigli et al. JACC Int 2012:5:268.

17. Tirofiban in STEMI – On-TIME 2 Trial
RCT of Pre-Hopital Tirofiban with Heparin
1073 Patients Treated with Stents, Preloaded Clopidogrel 600 mg
P = 0.02
P<0.001
P = 0.02
P = 0.30
Heestermans et al. J Thromb Haemostasis 2009;7:1612.

18. Bivalirudin vs Heparin or Heparin + Tirofiban in Acute MI
BRIGHT Trial
Bivalirudin vs Heparin or Heparin + Tirofiban in Acute MI
Bleeding Endpoints
Han et al. JAMA. 2015;313:1336.

19. GP IIb/IIIa and Ticagrelor
PLATO Trial – 9983 Pts with PCI within 72 Hours
(Ticagrelor vs Clopidogrel - GP IIb/IIIa use not randomized)
Ischemic Endpoint
GPI
No GPI
GPI
No GPI
Bleeding Endpoint
Shimada et al. AHJ 2016;177:1.

20. Antiplatelet Rx in STEMI
Should We Pretreat?
Aspirin – of course (but legacy)
Clopidogrel – reasonable
Prasugrel – No!
Ticagrelor – likely the best choice
Tirofiban – reasonable, but no evidence that it adds to ticagrelor
Cangrelor – more to come …

21. Heart and Vascular Institute