a randomized multicentre trial to evaluate the utilization ...massy - y. louvard (pi) 50 darmstadt -...
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A Randomized Multicentre Trial to
Evaluate the Utilization of
Revascularization or Optimal Medical
Therapy for the Treatment of Chronic
Total Coronary Occlusions
Gerald S. Werner, MD PhD
on behalf of the
EURO CTO trial investigators
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Speaker's name: Gerald S. Werner, MD
I do not have any potential conflict of interest to report:
Potential conflicts of interest
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Background
• 16-18% of all coronary lesions in stable coronary artery disease are chronic total occlusions (CTO)1,2
• Only 5% of PCI is performed in CTOs, many patients remain untreated3
1) Fefer P et al. J Am Coll Cardiol. 2012;59:991-9972) Råmunddal T. et Al. PLoS One. 2014;9:e1038503) Brilakis E. et al. JACC Cardiovasc Interv. 2015;8:245-53
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Study design
• Prospective, open-label, multi-centre randomisedtrial
• Primary efficacy endpoint: the effect of PCI as compared to OMT on the health status at 12 months follow-up as assessed by the Seattle Angina Questionnaire (SAQ)
• Primary safety endpoint: the safety of performing PCI as compared to OMT for a CTO in stable coronary artery disease during 3 years of follow-up.
• www.clinicaltrials.gov. NCT01760083
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TRIAL ORGANIZATION
PI: G. S. Werner
Steering
Committee:
E. Christiansen; I. Durand Zaleski; J. Escaned; A. Galassi
A.H. Gershlick; G. Heyndrickx ; D. Hildick-Smith ; Y. Louvard; G.
Olivecrona; G. Sianos; G. S. Werner (Chairperson)
Statistics: K. Bogaerts (KU Leuven)
DSMB: M Bertrand (Chair); C. Hamm; J-J. Goy
CEC: J. Machecourt (Chair), A. Baumbach, J. Garot
CRO: CERC, Massy, France
(Project Leader M. Carvalho)
e-CRF: Clinigrid
Sponsor: Euro-CTO Club (grant from Biosensors and Asahi)
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Major inclusion/exclusion criteria
• Patients with stable coronary artery disease and at least one CTO (TIMI 0, >3 months duration) with symptoms and/or ischemia and viability
• CTO location in a major artery (AHA 1-3, 6-7, 11) with a reference diameter ≥2.5mm
• Patients with multi-vessel disease should receive PCI to significant non-CTO lesions before randomisation; if the CTO needed treatment first, the patient was excluded
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Statistical design
• 1200 patients were planned to be enrolled to achieve a 90 % power for the safety endpoint at 36 months follow-up
• 600 patients were calculated as required for the primary efficacy endpoint
• The study inclusion started in March 2012 and was extended to May 2015, but the intended patient number to assess the primary endpoint was not reached, and the study concluded enrolment with 407 patients
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26 Participating centres/operatorsMassy - Y. LOUVARD (PI) 50
Darmstadt - G. WERNER/H. MOEHLIS (PI) 44
Barcelona - V. MARTIN YUSTE (PI) 43
Brighton - D. HILDICK-SMITH (PI) 40
Toulouse Cedex 9 - N. BOUDOU (PI) 29
Sofia – G. SIANOS/V. GELEV (PI) 28
GALDAKAO - R. RUMOROSO (PI) 27
Riga - A. ERGLIS (PI) 24
Aarhus N, - E. CHRISTIANSEN (PI) 19
Barcelona - L. TERUEL (PI) 15
London - C. DI MARIO (PI) 15
Madrid - J. ESCANED (PI) 15
Krefeld - A. BUFE (PI) 14
Bad Berka, - B. LAUER (PI) 10
Majadahonda - J. GOICOLEA (PI) 9
Edinburgh - J. SPRATT (PI) 8
Toulouse - D. TCHÉTCHÉ (PI) 4
Bad Soden/Taunus - N. REIFART (PI) 3
Barcelona - B. VAQUERIZO (PI) 3
Leicester - A. GERSHLICK (PI) 3
Bordeaux - J. LEYMARIE (PI) 2
Salerno - P. GIUDICE (PI) 2
Bad Krozingen - H. BÜTTNER (PI) 1
Catania - A. GALASSI (PI) 1
Rivoli - A. GAGNOR (PI) 1
Wolverhampton - J. COTTON (PI) 10
20
40
60
80
100
120
E F GB D BG LV DK I
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Efficacy: Health status @ 12 and 36 months
Safety: Death, non-fatal myocardial infarction (ITT, PP) @ 36 months
Single-vessel disease CTO onlyMultivessel CAD including CTO
Treat non-occlusive disease
by PCI before CTO with DES
Angina or
angina-
equivalent
symptoms
Study flow chart
48%
29%
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Efficacy: Health status @ 12 and 36 months
Safety: Death, non-fatal myocardial infarction (ITT, PP) @ 36 months
Single-vessel disease CTO onlyMultivessel CAD including CTO
Treat non-occlusive disease
by PCI before CTO with DES
Angina or
angina-
equivalent
symptoms
Randomisation 2:1
PCI with DES
+ OMT
n=259
2
OMT to include:
- Aspirin,
- Statin,
- ACE-inhibitor where tolerated
- + at least 2 anti-anginal agents at
max tolerated dose including rate-
limiting agent where appropriate.
Ischaemic symptoms should be
confirmed with non-invasive test.
OMT
n=137
1
Study flow chart
48%
29%
11 pats excluded
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Success Failure
Decision as per
usual clinical care
Medical Rx CABG
Efficacy: Health status @ 12 and 36 months
Safety: Death, non-fatal myocardial infarction (ITT, PP) @ 36 months
Repeat Exercise Tolerance Test (ETT) for objective assessment of ischemia @ 12m and 36months
Single-vessel disease CTO onlyMultivessel CAD including CTO
Treat non-occlusive disease
by PCI before CTO with DES
Angina or
angina-
equivalent
symptoms
Randomisation 2:1
PCI with DES
+ OMT
n=259
2
OMT to include:
- Aspirin,
- Statin,
- ACE-inhibitor where tolerated
- + at least 2 anti-anginal agents at
max tolerated dose including rate-
limiting agent where appropriate.
Ischaemic symptoms should be
confirmed with non-invasive test.
OMT
n=137
1
Study flow chart
48%
29%
Ongoing angina
despite OMT
n=10 (7.3%)
Clinically
indicated
interim PCI
11 pats excluded
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Patient characteristics I
OMT(N=137)
PCI(N=259)
Age (years) 64.7 ± 9.9 65.2 ± 9.7Male (%) 86.1 83.0BMI (kg/m²) 28.3 ± 5.2 28.4 ± 4.9Hypertension (%) 71.5 73.0Diabetes mellitus
Insulin-dependent (%) 8.8 8.5Non-Insulin-dependent (%) 20.4 24.3
Hypercholesterolaemia (%) 81.0 81.1History of Smoking (%) 67.2 73.4Family history (%) 26.3 31.3
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Patient characteristics II
OMT(N=137)
PCI(N=259)
Previous MI (%) 18.3 22.8Previous CABG (%) 7.3 13.1Previous PCI (%) 51.8 56.0PCI to facilitate study entry (%) 27.0 30.5LVEF (%) 55.7 ± 10.8 54.5± 10.8Myocardial viability (%) 85.4 86.1Number of diseased vessels
Single vessel (%) 45.3 50.2Two vessels (%) 37.2 24.3Three vessels (%) 17.5 25.5
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Lesion characteristics
OMT(N=137)
PCI(N=259)
Target vesselRCA (%) 57.4 63.7LAD (%) 27.0 25.5LCX (%) 15.6 10.8
Reference diameter (mm) 3.0 ± 0.41 2.9 ± 0.44Length of occlusion (mm) 26.5 ± 16.0 31.4 ± 20.5Lesion calcifications (%) 36.1 37.3Lesion tortuosity (%) 12.8 21.3J-CTO score 1.67 ± 0.91 1.82 ± 1.07
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PCI procedure in PCI group (n=255)
Radial approach for PCI (%) 34.3Bilateral approach (%) 81.2Retrograde approach (%) 35.8Revascularisation successful (%) 86.3Stents used
Biomatrix (%) 91.1Other DES (%) 8.9
Total length of stent used (mm) 65.9 ± 28.9Width of largest stent (mm) 3.3 ± 2.49Number of stents used 2.0 ± 1.32Procedure duration (min) 118.1 ± 67.2Fluoroscopy time (min) 48.8 ± 34.5
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Procedural complications
Any complication N(%) 8 (2.9)Death (%) 0Q-wave MI (%) 0Acute TVR/ emergency CABG (%) 0Pericardial tamponade (%) 4 (1.5)Vascular repair (%) 2 (0.7)Blood transfusion (%) 2 (0.7)
• 6 post procedural CK >3 times ULN, including 2 CK > 5 times ULN,
• 4 troponine increase. • None of the patients experienced pain or changes of
the ECG and CEC did not adjudicate any of them as 4aMI ( Universal definition)
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MACCE during follow-up
OMT(N=137)
PCI(N=259)
P-value
Patients with any adverse event 9 (6.7) 13 (5.2) 0.52All cause Death 0 2 (0.8) 0.55
Cardiac death 0 2 (0.8)Myocardial infarction 0 5 (1.9) 0.17
Non-Q-wave 0 4 (1.6)Q-wave 0 1 (0.4)
Ischemia-driven revascularization 9 (6.7) 7 (2.9) 0.10Cerebrovascular event 1 (0.7) 2 (0.8) 0.99Stent thrombosis 0 1 (0.4) 0.99
Number of patients (%)
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0
10
20
30
40
50
60
70
80
90
100
BL FU
Physical limitation
Anginalfrequency
Anginalstability
Treatmentsatisfaction
Quality oflife
Primary endpoint: SAQ health status (ITT)
For multiple testing the significance level is 0.01
BL FU BL FU BL FU BL FU BL FU BL FU BL FU BL FU BL FU BL FU
P=0.022
P=0.009P=0.049
P=0.89
P=0.47
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Significant change in SAQ subscale scores *)
0
10
20
30
40
50
60
70
80
90
100
Physical limitation ≥8
Anginal frequency ≥20
Freedom ofangina (100%)
Quality of life ≥16
OMT PCI
P=0.003 P=0.013 P=0.008 P=0.005
*) Spertus et al. JACC 1995;25:333-41
Sco
re
Higher score, better health status
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Changes in CCS class during follow-up
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Baseline Follow-up Baseline Follow-up
CCS 1 CCS 2 CCS 3 CCS 4OMT PCI
P<0.001
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Summary of results
• Due to slow recruitment the number of patients in this study is below the preplanned number
• However, the results are relevant and demonstrate, that PCI of CTO improved the health status regarding angina frequency, physical limitations, and quality of life as compared to OMT, and improved the functional class
• In experienced hands, periprocedural risk was low, and the 12 months MACCE rate was comparable to OMT, but the long-term safety remains to be evaluated at 36 months (Primary safety endpoint)
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BACKUP SLIDES
EUROCTO Trial
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CAD specific medication
0
10
20
30
40
50
60
70
80
90
100
BL FU BL FU BL FU BL FU BL FU BL FU BL FU
OMT PCI
Aspirin ADP ß-blocker ACEI/ARB
Statin Nitrate Ranolazineetc
P=0.04
P<0.001
P=0.006
P=0.14 P=0.009
P=0.16
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EQ-5D changes during follow-up
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
BL FU BL FU BL FU BL FU BL FU BL FU
No Moderate Severe
Mobility Activity Pain/discomfort
OMT PCI OMT PCI OMT PCI
P=0.001P<0.001P=0.005
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Primary endpoint: SAQ health status (ITT)
OMT(N=137)
PCI(N=259)
P-value
Available at baseline 133 (97%) 253 (98%)Available at follow-up 116 (85%) 209 (81%)Physical limitationBaseline 71.2 ± 24.7 67.1 ± 24.9Follow-up 76.7 ± 23.2 80.2 ± 22.4 0.04Angina frequencyBaseline 80.6 ± 24.2 77.2 ± 23.8Follow-up 87.5 ± 18.8 91.4 ± 16.6 0.02Quality of lifeBaseline 59.8 ± 26.2 55.3 ± 24.9Follow-up 72.1 ± 25.7 76.5 ± 23.1 0.06
Statistics: Analysis of covariance for changes in subscales between groups