A dministration of T icagrelor in the cath L ab or in the A mbulance for N ew S T elevation myocardial I nfarction to open the C oronary 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 � onset of ischaemic symptoms within 6 h � initially managed by ambulance � Documented evidence of STEMI Atlantic physician/personnel ; also concerning patients not � Planned for angioplasty (PCI) Population pre-treated for STEMI in emergency rooms of non-PCI hospitals STE-ACS planned for PCI (N = 1870) Randomised, double-blind Ticagrelor Placebo Pre-hospital 180 mg loading dose loading dose Placebo Ticagrelor In-Hospital loading dose 180 mg loading dose Primary Objectives ≥ ¡70% ¡ST -segment elevation TIMI flow grade 3 of MI culprit OR resolution pre-PCI vessel at initial angiography Ticagrelor 90 mg/bid 30 days Montalescot G et al. Am Heart J . 2013;165:515 – 522.
Median times to pre- and in-hospital steps Randomization EKG Onset of EKG Pre-hospital LD1 LD2 PCI Symptoms Pre-PCI Angiography 73 min 31 min 14 min 90 min 63 min 28 min 159 min
1 st Co-primary endpoint 2 nd Co-primary endpoint No ST- segment ¡resolution ¡(≥70%) No TIMI 3 flow in infarct-related artery Pre-hospital p = NS p = NS 100% 100% Pre-hospital In-hospital 87,6% 86,8% 90% 90% In-hospital 83,1% 82,6% 80% 80% patients (%) patients (%) 70% 70% p = 0.055 (NS) 60% 60% 47,5% 50% 50% 42,5% 40% 40% p = NS 30% 30% 19,6% 17,8% 20% 20% 10% 10% 0% 0% Pre-PCI Post-PCI Pre-PCI Post-PCI
Absence of ST-segment resolution by patient characteristics Odds ratio (95% CI) 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 0.0050 Yes 800 90.8% 86.8% 1.493 (0.954, 2.331) No 798 82.8% 88.4% 0.632 (0.423, 0.943) 0.5 1 2 Pre-hospital better In-hospital better
Definite stent thrombosis up to 30 days Ticagrelor pre-hospital 2% P=0.0078 P=0.0225 Ticagrelor in-hospital Event rate (KM %) 1% 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 24 0% 30 hrs days 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 Time (days)
Ticagrelor and definite stent thrombosis PLATO ATLANTIC In-hospital Ticagrelor vs. Clopidogrel Pre-hospital Ticagrelor vs. In-hospital ticagrelor 3% 3% Ticagrelor pre-hospital Ticagrelor Ticagrelor in-hospital Clopidogrel 2% 2% Ticagrelor pre-hospital 2/906 (0.2%) versus Event rate (KM %) Event rate (%) ticagrelor in-hospital 11/952 (1.2%) OR 0.19 (95% CI 0.04, 0.86), P=0.0225 1% 1% HR=0.67; 95% CI=0.50 – 0.91; p=0.009 0% 0% 0 60 120 180 240 300 360 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 Time from PCI/randomisation (days) Time (days) 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 10% Pre-hospital In-hospital 5% patients (%) p = NS p = NS p = NS p = NS p = NS p = NS 2,6% 2,5% 2,0% 1,8% 1,7% 1,6% 1,2% 1,2% 0,9% 0,9% 0,8% 0,5% 0% Major Minor Composite of Major Minor Composite of major and minor major and minor Within 48h of first dose After 48h up to 30 days
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 .
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