Ticagrelor vs Aspirin in Patients undergoing Coronary- Artery Bypass - PowerPoint PPT Presentation

The TiCAB Trial Ticagrelor vs Aspirin in Patients undergoing Coronary- Artery Bypass Grafting Herib eribert Schun unker ert, M , MD on behalf of the e TiCAB Investigators

TiCAB – an investigator initiated trial Sponsor Deutsches Herzzentrum München Lazarettstr. 36 80636 Munich, Germany Facilitated through a grant by AstraZeneca GmbH A Ran Randomized, Paral , Parallel G Gro roup, D , Double-Bl Blind Stu Study o y of f Ti Ticagrel relor Compare red w with A Aspiri rin fo for r Prevention o Preve of Vas f Vascular Eve ar Events i in Pati Patients U Underg rgoing Coro ronary A ry Artery rtery Byp ypass G Graft raft O Operat eration* April 2013 to May 2018 * de Waha et al Am Heart J. 2016;179:69-76

TiCAB Investigators • Steering Committee Prof. Dr. H. Schunkert, Prof. Dr. A. Böning, Prof. Dr. J. Cremer, Prof. Dr. C. Hamm, Prof. Dr. A. Kastrati, Prof. Dr. R. Lange, Prof. Dr. K. Laugwitz, Prof. Dr. S. Massberg, Prof. Dr. P. Radke, Ass.-Prof. Dr. S. Sandner, Prof. Dr. R. Schulz, Prof. Dr. H.-H. Sievers, Prof. Dr. U. Zeymer • Principal Investigators Prof. Dr. H. Schunkert, Prof. Dr. S. Sandner, Prof. Dr. A. Böning, Prof. Dr. R. Hambrecht, PD Dr. T. Attmann, Dr. M. Oberhoffer, PD Dr. C. Knosalla, Prof. Dr. T. Walther, PD Dr. B. Danner, Prof. Dr. M. Misfeld, Prof. Dr. G. Wimmer-Greinecker, Prof. Dr. U. Zeymer, Prof. Dr. M. Siepe, PD Dr. H. Grubitzsch, Dr. A. Joost, Dr. L. Conradi, Prof. Dr. I. Friedrich, Prof. Dr. L. Englberger, Prof. Dr. J. M. Albes, Prof. Dr. T. Fischlein, PD Dr. A. J. Rastan, Prof. Dr. M. Kelm, Prof. Dr. R. Autschbach, Dr. T. Sandhaus, Dr. J. Krülls-Münch, Prof. Dr. J. vom Dahl • Data Safety Monitoring Board Prof. Dr. M. Gottwik (Chair), Prof. Dr. H. Oelert, Prof. Dr. S. Hagl, Prof. Dr. T. Meinertz, Prof. Dr. K. Wegscheider • Event Adjudication Committee Prof. Dr. U. Tebbe (Chair), Prof. Dr. B. Nowak, Dr. J. Stritzke 3

TiCAB: Background Unmet Needs After CABG Surgery •Graft failure is related to major adverse events •Graft failure peaks in first year post surgery •More intense platelet inhibition has been shown to prevent graft failure – but •needs to be balanced for bleeding risks ISAResearch Center 4

Aspirin vs Ticagrelor after CABG - TiCAB Trial Study Hypothesis Ticagrelor, as compared to aspirin, reduces major adverse cardiovascular events within one year after CABG operation. ISAResearch Center 5

TiCAB: Power calculation STICH trial (CHF): N Engl J Med 2009 Mortality 12% at 1 year SYNTAX trial (3VD and LM): MACCE rate 12.4% at 1 year N Engl J Med 2009 PLATO-CABG (ACS): MACCE Ticagrelor/ Aspirin 10.6% Clopidogrel/ Aspirin: 13.1% JACC 2011 TiCAB (3VG, LM, 2VD+EF<50% - stable CAD and ACS) Primary end point: CV death, MI, stroke and revascularisation • estimated event rate: 13% in the control group • Two- sided α level of 0.0492 (0.05 adjusted for a planned interim analysis) • Power of 0.80 • Expected relative risk of 0.775 in the active group • Total of 3760 patients required ISAResearch Center 6

Aspirin vs Ticagrelor after CABG - TiCAB Trial Secondary Endpoints @ 12 months •Safety endpoint: Incidence of major bleeding events •Components of the primary endpoint: − Cardiovascular death − Myocardial infarction − Stroke − Recurrent revascularization ISAResearch Center 7

Aspirin vs Ticagrelor after CABG - TiCAB Trial Stratification Study Design Stable angina •Randomized ACS patients patients Randomisation •Double blind •Parallel group 1:1 Ticagrelor Aspirin Group Group •International multicenter 90mg twice daily or 100mg once daily for 12 months •Phase III study •with one planned interim analysis by the DSMB. 11.11.2018 ISAResearch Center 8

Aspirin vs Ticagrelor after CABG - TiCAB Trial Inclusion Criteria 1. Patients 18 years of age or older – and 2. Informed, written consent by the patient – and 3. Indication for CABG surgery – and - coronary three vessel disease, or - left main stenosis, or - two vessel disease with impaired EF (< 50%) 11.11.2018 ISAResearch Center 9

Aspirin vs Ticagrelor after CABG - TiCAB Trial Exclusion Criteria 1. Cardiogenic shock, haemodynamic instability 2. Indication for oral anticoagulation or dual antiplatelet therapy 3. Need for concomitant non-coronary surgery (e.g. valve replacement) 4. Contraindication for Aspirin or Ticagrelor use (e.g. known allergy) 5.... 11.11.2018 ISAResearch Center 10

Aspirin vs Ticagrelor after CABG - TiCAB Trial Follow-up •1 st Visit: CABG - Hospital visit •2 nd Visit: 3 months after CABG - Hospital visit •3 rd Visit: 6 months after CABG - Telephone visit •4 th Visit: 9 months after CABG - Telephone visit •5 th Visit: 12 months after CABG - Hospital visit 11.11.2018 ISAResearch Center 11

TiCAB Trial - Recruitment Total recruitment: Recruitment (cumulative) 1893 patients 04/2013 – 03/2017 2000 2000 1800 1800 1600 1600 1400 1400 tients nts 1200 1200 September 2016 of Pati cancelation of funding by 1000 1000 Number of the manufacturer of ticagrelor 800 800 Nu 600 600 400 400 200 200 0 un 13 13 Aug 13 Oct 13 13 Dec 13 13 Feb 14 14 Apr 14 r 14 un 14 14 Aug 14 Oct 14 14 Dec 14 14 Feb 15 15 r 15 Apr 15 un 15 15 Aug 15 15 Oct 15 15 Dec 15 Feb 16 16 Apr 16 r 16 un 16 Aug 16 16 Oct 16 16 Dec 16 16 Feb 16 16 Jun 1 Jun 1 Jun 1 Jun 1 Ap Ap Ap Au Au Au Au

Aspirin vs Ticagrelor after CABG - TiCAB Trial Follow-up • The trial was continued with in-house funding of the German Heart Center • The planned interim analysis by the DSMB was scheduled for March 2018 • The DSMB suggested the trial to be stopped ISAResearch Center 13

Aspirin vs Ticagrelor after CABG - TiCAB Trial Trial Enrollment, Randomization and Follow-up 11.11.2018 ISAResearch Center 14

Aspirin vs Ticagrelor after CABG - TiCAB Trial Baseline Characteristics (I)

Aspirin vs Ticagrelor after CABG - TiCAB Trial Baseline Characteristics (II)

Aspirin vs Ticagrelor after CABG - TiCAB Trial Results – CV death, MI, stroke, repeat revascularization Primary End Point Aspirin 30 HR 1.19 Ticagrelor 95% CI 0.87-1.62 Primary End Point (%) 25 P=0.27 20 15 9.7% 10 8.2% 5 0 0 2 4 6 8 10 12 Months after Enrollment ISAResearch Center 17

Aspirin vs Ticagrelor after CABG - TiCAB Trial Results – Secondary Endpoints Cardiovascular Death Myocardial infarction 30 30 Aspirin Aspirin Ticagrelor HR 0.85 HR 0.85 Ticagrelor HR HR 0.63 0.63 CI 0.38-1.89 25 25 CI 0.36-1.12 P=0.68 P=0.12 20 20 15 15 10 10 3.4% 5 5 1.4% 2.1% 0 0 1.2% 0 2 4 6 8 10 12 0 2 4 6 8 10 12 Months after Enrollment Months after Enrollment ISAResearch Center

Aspirin vs Ticagrelor after CABG - TiCAB Trial Results – Secondary Endpoints Stroke Revascularization Aspirin 30 30 Aspirin Ticagrelor Ticagrelor HR 1.28 HR 1.21 25 25 CI 0.82-2.00 CI 0.70-2.08 P=0.28 P=0.49 20 20 15 15 10 10 5.0% 3.2% 5 5 3.9% 2.6% 0 0 0 2 4 6 8 10 12 0 2 4 6 8 10 12 Months after Enrollment Months after Enrollment ISAResearch Center

Aspirin vs Ticagrelor after CABG - TiCAB Trial Results – MACE and Total mortality * MACE All Cause Death 30 30 Aspirin Aspirin HR 0.96 Ticagrelor Ticagrelor HR 0.99 25 25 CI 0.53-1.72 CI 0.69-1.42 P=0.89 P=0.94 20 20 15 15 10 10 6.5% 2.5% 5 6.3% 5 2.4% 0 0 0 2 4 6 8 10 12 0 2 4 6 8 10 12 Months after Enrollment Months after Enrollment *CV death, myocardial infarction or stroke

Aspirin vs Ticagrelor after CABG - TiCAB Trial Results – Bleeding events Bleeding (BARC 3, 4 and 5) Aspirin 30 HR 1.17 Ticagrelor CI 0.71-1.92 25 P=0.53 20 15 10 3.7% 5 3.2% 0 0 2 4 6 8 10 12 Months after Enrollment ISAResearch Center 21

Aspirin vs Ticagrelor after CABG - TiCAB Trial Results – Primary Endpoint Subgroup analysis ISAResearch Center 22

Aspirin vs Ticagrelor after CABG - TiCAB Trial Limitations of the Study The event rates were lower than expected • The study was terminated early after half of the anticipated • patients were included A main source of funding terminated the contract • Ticagralor displayed no signal for better outcome • The DSMB suggested to stop recruitment • ISAResearch Center 23

Aspirin vs Ticagrelor after CABG - TiCAB Trial Conclusion of the Study The use of ticagrelor monotherapy instead of aspirin monotherapy in patients undergoing CABG did not significantly impact the rates of major CV events nor major bleeding events. ISAResearch Center 24

Aspirin vs Ticagrelor after CABG - TiCAB Trial Tha Thank nk yo you for your our attention ntion!

T HANK YOU!