Ticagrelor vs Aspirin in Patients undergoing Coronary- Artery … · 2018-11-12 · Ticagrelor vs...
Transcript of Ticagrelor vs Aspirin in Patients undergoing Coronary- Artery … · 2018-11-12 · Ticagrelor vs...
Ticagrelor vs Aspirin in Patients undergoing Coronary-Artery Bypass Grafting
Heribert Schunkert, MDon behalf of
the TiCAB Investigators
The TiCAB Trial
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• Steering CommitteeProf. 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 InvestigatorsProf. 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 BoardProf. Dr. M. Gottwik (Chair), Prof. Dr. H. Oelert, Prof. Dr. S. Hagl,
Prof. Dr. T. Meinertz, Prof. Dr. K. Wegscheider
• Event Adjudication CommitteeProf. Dr. U. Tebbe (Chair), Prof. Dr. B. Nowak, Dr. J. Stritzke
TiCAB Investigators
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• Graft failure peaks in first year and is related to major adverse events
• Graft failure and other ischemic events may be prevented by more intensive platelet inhibition – but
• this needs to be balanced for bleeding risks
TiCAB: Background
After CABG Surgery
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Ticagrelor, as compared to aspirin,
reduces major adverse cardiovascular events
within one year after CABG operation.
Study Hypothesis
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•Randomized•Double blind•Parallel group •International multicenter•Phase III study•with one planned interim analysis by the DSMB.
Study Design Stratification
ACS patients
Stable anginapatientsRandomisation
Aspirin Group
TicagrelorGroup
1:1
90mg twice daily or 100mg once daily for 12 months
An investigator initiated trial partially funded through a grant by AstraZeneca
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• Incidence of:−Cardiovascular death −Myocardial infarction −Stroke−Recurrent revascularization
Primary Endpoint @ 12 months*
Aspirin vs Ticagrelor after CABG - TiCAB Trial
* Supported by a power calculation and incidence rates observed in STICH, SYNTAX and PLATO-CABG
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• Incidence of major bleeding events
Safety Endpoint @ 12 months*
Aspirin vs Ticagrelor after CABG - TiCAB Trial
* Periprocedural CABG and hospital stay-related: BARC 4 & 5Post-discharge: BARC ≥Type 3
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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
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1. Cardiogenic shock, haemodynamic instability2. Indication for oral anticoagulation or dual antiplatelet therapy 3. 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
Recruitment (cumulative)04/2013 – 03/2017
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September 2016cancelation of funding by
the manufacturer of ticagrelor
TiCAB Trial - Recruitment
3760 patients plannedby power calculation
Total recruitment:1893 patients
March 2018DSMB suggested
to stop the trial
Baseline Characteristics (I)Aspirin vs Ticagrelor after CABG - TiCAB Trial
Aspirin vs Ticagrelor after CABG - TiCAB Trial
Baseline Characteristics (II)
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Results – CV death, MI, stroke, repeat revascularization
Months after Enrollment
Prim
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Primary End PointAspirinTicagrelor HR 1.19
95% CI 0.87-1.62 P=0.27
8.2%
9.7%
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Results – Secondary Endpoints
Months after Enrollment
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Myocardial infarctionAspirinTicagrelor
Months after Enrollment
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Cardiovascular DeathAspirinTicagrelor
1.4%
1.2%
HR 0.85 CI 0.38-1.89 P=0.68
3.4%
2.1%
HR 0.63 CI 0.36-1.12 P=0.12
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Results – Secondary Endpoints
Months after Enrollment
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Revascularization
AspirinTicagrelor
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StrokeAspirinTicagrelor
HR 1.21 CI 0.70-2.08 P=0.49
5.0%
3.9%
3.2%
2.6%
HR 1.28CI 0.82-2.00P=0.28
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Results – MACE and Total mortality
Months after Enrollment
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MACEAspirinTicagrelor
Months after Enrollment
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All Cause DeathAspirinTicagrelor
2.5%
2.4%
6.5%
6.3%
HR 0.99 CI 0.69-1.42P=0.94
HR 0.96CI 0.53-1.72P=0.89
*CV death, myocardial infarction or stroke
*
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Results – Bleeding events
Months after Enrollment
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Bleeding (BARC 3, 4 and 5)AspirinTicagrelor
3.7%
3.2%
HR 1.17 CI 0.71-1.92P=0.53
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Results –Primary Endpoint
Subgroup analysis
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• 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
• The DSMB suggested to stop recruitment
• Ticagrelor displayed no signal for better outcome
Limitations of the Study
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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
Thank you for your attention!
Aspirin vs Ticagrelor after CABG - TiCAB Trial
THANK YOU!
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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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Trial Enrollment, Randomization and Follow-up
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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
Deutsches Herzzentrum MünchenLazarettstr. 3680636 Munich, Germany
Facilitated through a grant by AstraZeneca GmbH
A Randomized, Parallel Group, Double-Blind Study of Ticagrelor Compared with Aspirin for Prevention of Vascular Events in Patients Undergoing
Coronary Artery Bypass Graft Operation*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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•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