A dministration of T icagrelor in the cath L ab or in the A mbulance - - PowerPoint PPT Presentation

Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial Infarction to

• pen the Coronary artery
• G. Montalescot, for the ATLANTIC investigators
• Dr. Montalescot reports receiving consulting fees from AstraZeneca, Bayer, Biotronik,

Boehringer Ingelheim, Bristol-Myers Squibb, Cardiovascular Research Foundation, Daiichi- Sankyo, Eli Lilly, Europa Organisation, the Gerson Lehrman Group, Iroko Cardio International, Lead-Up, Luminex, McKinsey & Company Inc., Remedica, Servier, TIMI Study Group, WebMD, Wolters Kluwer Health, Medicines Company, Medtronic, Menarini Group, Pfizer, Roche, Sanofi-Aventis, and grant support from Abbott Laboratories, Accumetrics, AstraZeneca, Biotronik, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Medicines Company, Medtronic, Menarini Group, Nanosphere Inc., Pfizer, Roche, Sanofi-Aventis and Stentys.

Study population and design

Montalescot G et al. Am Heart J. 2013;165:515–522.

STE-ACS planned for PCI (N = 1870)

Ticagrelor 180 mg loading dose Placebo loading dose Pre-hospital Placebo loading dose Ticagrelor 180 mg loading dose In-Hospital Primary Objectives

Randomised, double-blind

≥ ¡70% ¡ST-segment elevation resolution pre-PCI TIMI flow grade 3 of MI culprit vessel at initial angiography OR Ticagrelor 90 mg/bid 30 days

Documented evidence of STEMI Planned for angioplasty (PCI)

Atlantic Population

• nset of ischaemic symptoms within 6 h

initially managed by ambulance physician/personnel; also concerning patients not pre-treated for STEMI in emergency rooms of non-PCI hospitals

73 min 31 min 14 min 90 min 63 min 28 min 159 min

Median times to pre- and in-hospital steps

Onset of Symptoms EKG Pre-hospital LD1

LD2

EKG Pre-PCI Angiography

PCI Randomization

86,8% 42,5% 87,6% 47,5%

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Pre-PCI Post-PCI

Pre-hospital In-hospital

patients (%) p = NS p = 0.055 (NS)

82,6% 17,8% 83,1% 19,6%

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Pre-PCI Post-PCI

Pre-hospital In-hospital

patients (%) p = NS p = NS

1st Co-primary endpoint No ST-segment ¡resolution ¡(≥70%)

2nd Co-primary endpoint

No TIMI 3 flow in infarct-related artery

Absence of ST-segment resolution by patient characteristics

Characteristic Total patients Endpoint rate P Value

Age Pre-hospital In-hospital OR (95% CI) (Int.) <65 years 1014 85.9% 87.3% 0.887 (0.618, 1.272) 0.6207 ≥65 ¡years 584 88.6% 88.2% 1.037 (0.625, 1.724) <75 years 1348 86.7% 86.8% 0.994 (0.726, 1.362) 0.2940 ≥75 ¡years 250 87.6% 92.0% 0.617 (0.269, 1.418) Sex Male 1288 87.0% 87.7% 0.945 (0.680, 1.312) 0.8292 Female 310 85.9% 87.5% 0.871 (0.451, 1.684) Diabetes Yes 212 88.3% 88.1% 1.015 (0.438, 2.353) 0.8319 No 1386 86.6% 87.5% 0.922 (0.673, 1.261) Location of MI Anterior 831 89.0% 87.3% 1.183 (0.775, 1.808) 0.1320 Non-anterior 767 84.7% 88.0% 0.750 (0.495, 1.136) TIMI risk score 0–2 971 86.0% 87.6% 0.867 (0.597, 1.256) 0.7129 3–6 599 88.3% 87.4% 1.081 (0.661, 1.767) >6 28 86.7% 92.3% 0.542 (0.043, 6.757) Highest Killip Classifiation pre-PCI I 1458 86.1% 88.2% 0.833 (0.612, 1.133) 0.1049 >I 82 93.5% 83.3% 2.865 (0.664, 12.236) Prior ASA use Yes 476 88.8% 87.1% 1.178 (0.670, 2.075) 0.3455 No 1122 86.1% 87.9% 0.856 (0.604, 1.214) GPIIb/IIIa inhibitor use before angiography Yes 117 85.2% 83.9% 1.106 (0.405, 3.021) 0.7281 No 1481 87.0% 87.9% 0.918 (0.675, 1.248)

Morphine use for index event/PCI

Yes 800 90.8% 86.8% 1.493 (0.954, 2.331)

0.0050

No 798 82.8% 88.4% 0.632 (0.423, 0.943)

Pre-hospital better In-hospital better

1 0.5 2

Odds ratio (95% CI)

Definite stent thrombosis up to 30 days

0% 1% 2% 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30

Ticagrelor pre-hospital Ticagrelor in-hospital

Event rate (KM %) Time (days)

Ticagrelor pre-hospital 2/906 (0.2%) versus Ticagrelor in-hospital 11/952 (1.2%) OR 0.19 (95% CI 0.04, 0.86), P=0.0225

P=0.0225

30

days

P=0.0078

24 hrs

Ticagrelor and definite stent thrombosis

PLATO

In-hospital Ticagrelor vs. Clopidogrel

ATLANTIC

Pre-hospital Ticagrelor vs. In-hospital ticagrelor

0% 1% 2% 3% 60 120 180 240 300 360

Ticagrelor Clopidogrel

Time from PCI/randomisation (days) Event rate (%)

HR=0.67; 95% CI=0.50–0.91; p=0.009

0% 1% 2% 3% 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30

Ticagrelor pre-hospital Ticagrelor in-hospital

Time (days) Event rate (KM %)

Ticagrelor pre-hospital 2/906 (0.2%) versus ticagrelor in-hospital 11/952 (1.2%) OR 0.19 (95% CI 0.04, 0.86), P=0.0225 Steg PG, et al. Circulation 2013;128:1055–1065. Montalescot G, et al. ESC sept 1st 2014.

Non-CABG-related bleeding events

(PLATO definitions) - Safety population

1,8% 0,9% 2,6% 1,2% 0,8% 2,0% 1,6% 0,9% 2,5% 1,2% 0,5% 1,7%

0% 5% 10%

Major Minor Composite of major and minor Major Minor Composite of major and minor

Pre-hospital In-hospital

Within 48h of first dose After 48h up to 30 days p = NS p = NS p = NS p = NS p = NS p = NS patients (%)

Conclusion

Pre-hospital ticagrelor administration a short time before PCI in patients with ongoing STEMI is safe but does not improve pre-PCI coronary

• reperfusion. It may, however, reduce the risk of

post-PCI stent thrombosis.