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

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

Jan 07, 2024 547 likes •828 views

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

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SLIDE 1

Ticagrelor vs Aspirin in Patients undergoing Coronary- Artery Bypass Grafting

Herib eribert Schun unker ert, M , MD

  • n behalf of

the e TiCAB Investigators

The TiCAB Trial

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SLIDE 2

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 Preve Prevention o

  • f 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

Sponsor

TiCAB – an investigator initiated trial

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SLIDE 3

3

  • 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

TiCAB Investigators

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SLIDE 4

ISAResearch Center 4

  • 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

Unmet Needs After CABG Surgery TiCAB: Background

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SLIDE 5

ISAResearch Center 5

Ticagrelor, as compared to aspirin, reduces major adverse cardiovascular events within one year after CABG operation. Study Hypothesis

Aspirin vs Ticagrelor after CABG - TiCAB Trial

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SLIDE 6

ISAResearch Center 6

SYNTAX trial (3VD and LM): MACCE rate 12.4% at 1 year STICH trial (CHF): Mortality 12% at 1 year PLATO-CABG (ACS): MACCE Ticagrelor/ Aspirin 10.6% Clopidogrel/ Aspirin: 13.1%

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

N Engl J Med 2009 N Engl J Med 2009 JACC 2011

TiCAB: Power calculation

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SLIDE 7

ISAResearch Center 7

  • Safety endpoint: Incidence of major bleeding events
  • Components of the primary endpoint:

−Cardiovascular death −Myocardial infarction −Stroke −Recurrent revascularization

Secondary Endpoints @ 12 months

Aspirin vs Ticagrelor after CABG - TiCAB Trial

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SLIDE 8

11.11.2018 ISAResearch Center 8

  • Randomized
  • Double blind
  • Parallel group
  • International multicenter
  • Phase III study
  • with one planned interim analysis by the DSMB.

Study Design

Stratification

ACS patients Stable angina patients

Randomisation

Aspirin Group Ticagrelor Group

1:1

90mg twice daily or 100mg once daily for 12 months

Aspirin vs Ticagrelor after CABG - TiCAB Trial

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SLIDE 9

11.11.2018 ISAResearch Center 9

  • 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%)

Inclusion Criteria

Aspirin vs Ticagrelor after CABG - TiCAB Trial

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SLIDE 10

11.11.2018 ISAResearch Center 10

  • 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....

Exclusion Criteria

Aspirin vs Ticagrelor after CABG - TiCAB Trial

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SLIDE 11

11.11.2018 ISAResearch Center 11

  • 1st Visit: CABG
  • Hospital visit
  • 2nd Visit: 3 months after CABG - Hospital visit
  • 3rd Visit: 6 months after CABG
  • Telephone visit
  • 4th Visit: 9 months after CABG
  • Telephone visit
  • 5th Visit: 12 months after CABG - Hospital visit

Follow-up

Aspirin vs Ticagrelor after CABG - TiCAB Trial

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SLIDE 12

Total recruitment: 1893 patients Recruitment (cumulative) 04/2013 – 03/2017

200 200 400 400 600 600 800 800 1000 1000 1200 1200 1400 1400 1600 1600 1800 1800 2000 2000 Jun 1 un 13 Au Aug 13 13 Oct 13 13 Dec 13 13 Feb 14 14 Ap Apr 14 r 14 Jun 1 un 14 Au Aug 14 14 Oct 14 14 Dec 14 14 Feb 15 15 Ap Apr 15 r 15 Jun 1 un 15 Au Aug 15 15 Oct 15 15 Dec 15 15 Feb 16 16 Ap Apr 16 r 16 Jun 1 un 16 Au Aug 16 16 Oct 16 16 Dec 16 16 Feb 16 16 Nu Number of

  • f Pati

tients nts

September 2016 cancelation of funding by the manufacturer of ticagrelor

TiCAB Trial - Recruitment

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ISAResearch Center 13

Follow-up

Aspirin vs Ticagrelor after CABG - TiCAB Trial

  • 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
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SLIDE 14

11.11.2018 ISAResearch Center 14

Trial Enrollment, Randomization and Follow-up

Aspirin vs Ticagrelor after CABG - TiCAB Trial

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SLIDE 15

Baseline Characteristics (I)

Aspirin vs Ticagrelor after CABG - TiCAB Trial

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SLIDE 16

Aspirin vs Ticagrelor after CABG - TiCAB Trial

Baseline Characteristics (II)

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ISAResearch Center 17

Results – CV death, MI, stroke, repeat revascularization

Months after Enrollment Primary End Point (%) 5 10 15 20 25 30

2 4 6 8 10 12

Primary End Point

Aspirin Ticagrelor

HR 1.19 95% CI 0.87-1.62 P=0.27

8.2% 9.7%

Aspirin vs Ticagrelor after CABG - TiCAB Trial

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SLIDE 18

ISAResearch Center

Results – Secondary Endpoints

Months after Enrollment 5 10 15 20 25 30

2 4 6 8 10 12

Myocardial infarction

Aspirin Ticagrelor

Months after Enrollment 5 10 15 20 25 30

2 4 6 8 10 12

Cardiovascular Death

Aspirin Ticagrelor

1.4% 1.2% HR HR 0.85 0.85 CI 0.38-1.89 P=0.68 3.4% 2.1% HR HR 0.63 0.63 CI 0.36-1.12 P=0.12

Aspirin vs Ticagrelor after CABG - TiCAB Trial

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SLIDE 19

ISAResearch Center

Results – Secondary Endpoints

Months after Enrollment 5 10 15 20 25 30

2 4 6 8 10 12

Revascularization

Aspirin Ticagrelor

Months after Enrollment 5 10 15 20 25 30

2 4 6 8 10 12

Stroke

Aspirin Ticagrelor

HR 1.21 CI 0.70-2.08 P=0.49 5.0% 3.9% 3.2% 2.6% HR 1.28 CI 0.82-2.00 P=0.28

Aspirin vs Ticagrelor after CABG - TiCAB Trial

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SLIDE 20

Results – MACE and Total mortality

Months after Enrollment 5 10 15 20 25 30

2 4 6 8 10 12

MACE

Aspirin Ticagrelor

Months after Enrollment 5 10 15 20 25 30

2 4 6 8 10 12

All Cause Death

Aspirin Ticagrelor

2.5% 2.4% 6.5% 6.3% HR 0.99 CI 0.69-1.42 P=0.94 HR 0.96 CI 0.53-1.72 P=0.89 *CV death, myocardial infarction or stroke

*

Aspirin vs Ticagrelor after CABG - TiCAB Trial

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ISAResearch Center 21

Results – Bleeding events

Months after Enrollment 5 10 15 20 25 30

2 4 6 8 10 12

Bleeding (BARC 3, 4 and 5)

Aspirin Ticagrelor

3.7% 3.2% HR 1.17 CI 0.71-1.92 P=0.53

Aspirin vs Ticagrelor after CABG - TiCAB Trial

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ISAResearch Center 22

Results – Primary Endpoint Subgroup analysis

Aspirin vs Ticagrelor after CABG - TiCAB Trial

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ISAResearch Center 23

  • 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

Limitations of the Study

Aspirin vs Ticagrelor after CABG - TiCAB Trial

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SLIDE 24

ISAResearch Center 24

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. Conclusion of the Study

Aspirin vs Ticagrelor after CABG - TiCAB Trial

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Tha Thank nk yo you for your

  • ur attention

ntion!

Aspirin vs Ticagrelor after CABG - TiCAB Trial

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T HANK YOU!