Ticagrelor vs prasugrel in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention

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1 DISCLOSURES: NONE

2 Ticagrelor vs prasugrel in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention I. Xanthopoulou, KC. Theodoropoulos, G. Kassimis, V. Gizas, G. Tsigkas, N. Koutsogiannis, P. Davlouros, J. Chiladakis, G. Hahalis, D. Alexopoulos Patras University Hospital, Cardiology Department, Patras, Greece Unique identifier: NCT

3 Purpose Ticagrelor and prasugrel provide stronger platelet inhibition compared to clopidogrel. The early and efficient platelet inhibition is important in the clinical setting of ST elevation myocardial infarction (STEMI). Limited data exist about the onset of action and the degree of platelet inhibition achieved by ticagrelor and prasugrel early in patients with STEMI undergoing primary percutaneous coronary intervention (PCI).

4 Methods I Prospective, randomized, single-center, single blind study of parallel design. P2Y12 inhibitor-naïve patients with STEMI (pain onset<12 h) were screened for eligibility upon hospital admission Randomization in the cath lab after coro angiography Ticagrelor 180mg LD 90mg x 2 MD Prasugrel 60mg LD 10mg MD

5 Methods II Platelet reactivity (PR) assessment was performed at Hour 0 (Rando), 1, 2, 6, 24 and at Day 5 with the P2Y12 VerifyNow assay and Multiplate analyzer High platelet reactivity (HPR) 230 PRU for VerifyNow assay 468 AU/min for Multiplate analyzer

6 Exclusion criteria Prior stroke/transient ischemic attack Bleeding diathesis Chronic oral anticoagulation Previous P2Y12 inhibitor treatment Use of strong CYP3A inhibitor or inducer Hemodynamic instability Methods III Platelet count <100000/μL Hematocrit <30% or >52% CrCl <30 ml/min Severe hepatic dysfunction Increased risk of bradycardia Severe chronic obstructive pulmonary disease Periprocedural IIb/IIIa inhibitor administration

7 Methods IV Primary endpoint PR (VerifyNow assay) at Hour 1 between the 2 treatment groups. Secondary endpoints PR at Hour 2, 6, 24 and Day 5 HPR rate at Hour 1, 2, 6, 24 and Day 5 MACEs (death, myocardial infarction, urgent revascularization and stroke) and bleeding (TIMI major, minor and minimal) were monitored until Day 5

8 Between Sep 2011 and April 2012 Consecutive patients with STEMI N=117 Exclusion criterion fulfillment N=62 IIb/IIIa administration N=3 Haemodynamic instability N=13 Prior stroke N=1 Anatomy not suitable for primary PCI N=12 Eligible patients N=55 Randomized N=55 Hemodialysis N=1 Antiplatelet non-naive N=18 Chronic oral anticoagulation N=6 Bradycardia N= 4 Pain onset >12 hours N=3 Dementia N=1 Allocated to Ticagrelor N=28 1 patient died at Day 5 Patients with Day 5 data N=27 Allocated to prasugrel N=27 3 patients died (2 at Day 1 and 1 at Day 4) Patients with Day 5 data N=24

9 Demographic and clinical characteristics of randomized patients Overall Ticagrelor Prasugrel N=55 N=28 N=27 p-value Male gender 44(80.0) 24(85.7) 20(74.1) 0.3 Age (years) 59.5± ± ± BMI (Kg/m²) 28.6± ± ± Diabetes mellitus 5(9.1) 3(10.7) 2(7.4) 1.0 Smoking 31(56.4) 18(64.3) 13(48.1) 0.3 Statin 37(67.3) 19(66.9) 18(66.7) 1.0 PPI 29(52.7) 16(57.1) 13(48.1) 0.6 Bivalirudin 34(61.8) 14(50.0) 20(74.1) 0.1 CrCl <60 ml/min 5(9.1) 1(3.6) 4(14.8) 0.2 Pain-to-balloon (hours) 3(0.7-12) 3.0(0.7-8) 3.0(0.7-12) 0.06 Rando-to-balloon (mins) 10.0± ± ± PR pre rando (PRU) 240.9± ± ± PR pre rando (AU/min) N=43 N=23 N= ± ± ±

10 PR (in PRU) at 1, 2, 6, 24 hours and Day 5 post randomization Time post randomization Ticagrelor LS estimates (95%CI) 1 hour ( ) 2 hours ( ) 6 hours 75.2 ( ) 24 hours 46.7 ( ) Day ( ) Prasugrel LS estimates (95%CI) ( ) ( ) 69.4 ( ) 40.8 ( ) 50.3 ( ) LS mean difference (95%CI) 25.9 (-11.2 to 63.1) 42.6 p-value 0.2 (-19.3 to 104.5) (-38.8 to 50.4) (-23.6 to 35.4) (-43.9 to -5.4) 0.01 Mixed effects models with treatment as fixed effect, patient as a random intercept and platelet reactivity at baseline as a covariate.

11 PR (in AU/min) at 1, 2, 6, 24 hours and Day 5 post rando Time post rando Ticagrelor LS estimates (95%CI) 1 hour ( ) 2 hours ( ) 6 hours ( ) 24 hours ( ) Day ( ) Prasugrel LS estimates (95%CI) ( ) ( ) ( ) ( ) ( ) LS mean difference (95%CI) (-63.0 to 293.9) 59.4 p-value 0.2 (-90.2 to 209.0) (-91.1 to 70.9) (-62.6 to 62.8) ( to 3.6) 0.06 Mixed effects models with treatment as fixed effect, patient as a random intercept and platelet reactivity at baseline as a covariate.

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15 Safety 1 patient allocated to ticagrelor arm died at Day 5 from stroke 2 patients allocated to prasugrel arm died at Day 1 from pump failure and 1 patient also allocated to prasugrel died at Day 4 during emergency operation for ruptured papillary muscle No major bleedings occurred in either treatment arm

16 Conclusions In patients with STEMI undergoing primary PCI ticagrelor and prasugrel did not differ significantly in their antiplatelet action during the first 24 hours post LD HPR rates remained high up to 2 hours post LD and effectively decreased thereafter by both agents

17 Thank you for your attention