Ticagrelor With Asp Irin or ALone In Hi

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Ticagrelor With Asp. Irin or ALone In Hi. GH-Risk Patients After Coronary In. Tervention

Ticagrelor With Asp. Irin or ALone In Hi. GH-Risk Patients After Coronary In. Tervention Study Status Update Global Principal Investigator: Roxana Mehran, MD Sponsor/ARC: Icahn School of Medicine at Mount Sinai, New York, NY Funding Agency: Astra. Zeneca

Disclosure Statement of Financial Interest I, Usman Baber, DO NOT have a financial interest/arrangement

Disclosure Statement of Financial Interest I, Usman Baber, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

Outline • Study Rationale • Study Design • Current Study Status • Cohort Characteristics

Outline • Study Rationale • Study Design • Current Study Status • Cohort Characteristics • Future Directions NCT 02270242; Usman Baber, MD, MS et al. , Rational and Design of the TWILIGHT Study, http: //dx. doi. org/10. 1016/j. ahj. 2016. 09. 00

Background/Rationale DUAL ANTIPLATELET THERAPY AFTER PCI: EVOLVING PARADIGMS § Early (3 -6 months) Antiplatelet

Background/Rationale DUAL ANTIPLATELET THERAPY AFTER PCI: EVOLVING PARADIGMS § Early (3 -6 months) Antiplatelet Therapy After PCI § For reduction in stent-related thrombotic events § Equipoise for shorter DAPT durations (safer stent platforms, bleeding avoidance strategies) § Late (6 -9 months) Antiplatelet Therapy After PCI § For reduction in systemic thrombosis § Optimal approach remains unknown § Residual high thrombotic risk persists despite treatment with ASA/Clopidogrel in certain high-risk patients (DM, CKD, ACS) NCT 02270242; Usman Baber, MD, MS et al. , Rationale and Design of the TWILIGHT Study, AHJ 2016

Background/Rationale ACUITY trial – correlation between thrombotic and bleeding risk Pocock et al, Circulation

Background/Rationale ACUITY trial – correlation between thrombotic and bleeding risk Pocock et al, Circulation 2010 Mortality after MI or bleeding Mehran et al, EHJ 2010

TWILIGHT: Primary Aim Test the efficacy and safety of an antiplatelet strategy to lower

TWILIGHT: Primary Aim Test the efficacy and safety of an antiplatelet strategy to lower bleeding risk while not incurring excess thrombosis in high risk patients undergoing PCI with DES

Study Design SOC THERAPY N = 8200 RANDOMIZATION PERIOD ENDS TICAGRELOR + ASA OBSERVATION

Study Design SOC THERAPY N = 8200 RANDOMIZATION PERIOD ENDS TICAGRELOR + ASA OBSERVATION PERIOD STARTS TICAGRELOR + ASA RANDOMIZE HIGH RISK PCI PATIENTS, N = 9000 Multicenter, prospective, blinded dual-arm study TICAGRELOR + Placebo SOC THERAPY 3 MONTHS 12 MONTHS 3 MONTHS Short course DAPT to minimize stentrelated thrombotic events Monotherapy with potent platelet inhibitor provides ischemic protection while reducing ASA related bleeding TICAGRELOR + ASA Observational period

INCLUSION CRITERIA Clinical Inclusion Criteria *Must meet ≥ 1 of the below Angiographic Inclusion

INCLUSION CRITERIA Clinical Inclusion Criteria *Must meet ≥ 1 of the below Angiographic Inclusion Criteria *Must meet ≥ 1 of the below • Adult patients ≥ 65 years of age • Multi-vessel CAD • Female sex • Target lesion requiring total stent length >30 mm • Troponin positive acute coronary syndrome • Thrombotic target lesion(s) • Established Vascular Disease • Bifurcation lesion (X, 1, 1) requiring at least 2 stents • Diabetes mellitus requiring medications • Left Main (≥ 50%) lesion OR Proximal LAD (≥ 70%) lesion CKD (e. GFR <60 ml/min/1. 73 m 2 OR Cr. Cl <60 ml/min) • Calcified target lesion(s) requiring atherectomy •

Trial Assumptions • Enrolled Sample ~ 9, 000 • Randomized Sample ~ 8, 200

Trial Assumptions • Enrolled Sample ~ 9, 000 • Randomized Sample ~ 8, 200 • Primary Endpoint: BARC 2, 3, 5 bleeding between months 3 and 15; superiority hypothesis • Key Ischemic Endpoint: all-cause death, MI, stroke; noninferiority hypothesis • Primary Endpoint Rate between 3 -15 months: 4. 5%

Overall Trial Status As of 17 -Feb-2017 Enrollment, Cumulative 3859 Randomization, Cumulative 1912 Sites

Overall Trial Status As of 17 -Feb-2017 Enrollment, Cumulative 3859 Randomization, Cumulative 1912 Sites Activated 128 Sites Enrolling 120 Countries Activated US, Canada, Italy, Austria, Spain, Israel, India, UK, China, Germany, Poland Countries Enrolling 10

Enrollment Progress 500 6 5. 5 450 5. 08 4. 93 5 3. 92

Enrollment Progress 500 6 5. 5 450 5. 08 4. 93 5 3. 92 3. 72 300 3. 76 3. 44 3. 66 3. 48 3. 37 3. 71 3. 85 3. 8 3. 53 4 3. 12 2. 88 3. 27 250 3 200 2 150 100 1 50 Actual Enrollment 448 7 Ja 16 ec - D ov - 6 N 395 n 1 404 16 364 ct -1 O Se p Au g Patients/Site/Month 345 -1 6 242 -1 6 206 l-1 6 Ju 6 212 n 1 Ju -1 6 150 ay M r-1 Ap ar 167 6 6 188 -1 16 145 M 6 91 Fe b- 15 Ja ec D ov - 5 N 79 n 1 74 15 61 ct -1 O Se p -1 5 31 -1 5 11 0 0 Patients/Site/Month 4. 18 350 Au g Patients enrolled per month 400

Enrollment by Region 11% US 2% Canada 3% EU 16% 54% Israel India 13%

Enrollment by Region 11% US 2% Canada 3% EU 16% 54% Israel India 13% China

Characteristics in Enrolled Patients Parameter Age, years Female sex, % Value 64 25% DM,

Characteristics in Enrolled Patients Parameter Age, years Female sex, % Value 64 25% DM, % 40. 2% PAD, % 9% ACS 62% SCr > 1. 2 18% Stent length, mean 36 mm MV PCI, % 22% Prox LAD or LM PCI, % 35%

Future Directions • Onboarding final sites in Poland & China • Last Patient Enrolled:

Future Directions • Onboarding final sites in Poland & China • Last Patient Enrolled: 31 -Dec-2017 • Last Patient Follow up: 30 -Mar-2019

TWILIGHT Study Design paper

TWILIGHT Study Design paper

Thank You!

Thank You!