Euro CTO Club – The Euro CTO trial Gerald S. Werner, Germany The Experts “Live” Workshop 2017 Friday, September 15th, 2017

1. The EURO CTO Trial
Outcomes and Perspective
Gerald S. Werner FESC, FACC, FSCAI
Visiting Professor Clinical Center Serbia
Klinikum Darmstadt GmbH
Darmstadt

2. The rational for CTO PCI
• Improvement of clinical symptoms
– Relief of angina and ischemia
– Improvement of physical capacity
– Improved prognosis ?

3. Overall Mortality and CTO Success
Successful PCI of at least 1 CTO was associated with improved survival
(hazard ratio [HR]: 0.72; 95% CI: 0.62 to 0.83; p < 0.001)
Sudhakar et al. J Am Coll Cardiol. 2014;64:235-243

4. Symptomatic relief by PCI demonstrated in many trials
Joyal D et al. Am Heart J 2010;160:179-87
Comparison between successful and failed procedures

5. What can we expect from a randomized trial ?
• Randomized trials will always include less
symptomatic patients
• There will be less clinical events than in a
consecutive registry patient cohort
• There will never be a randomized trial
showing mortality differences for CTO PCI

6. DECISION-CTO
Optimal Medical Therapy With or Without
Stenting For Coronary Chronic Total Occlusion
Seung-Jung Park, MD., PhD.
Heart Institute, University of Ulsan College of Medicine
Asan Medical Center, Seoul, Korea

7. Study Flow
834 patients randomized
from 2010.3.22 to 2016.10.10
417 allocated to PCI398 allocated to OMT
310 treated with OMT
72 treated with PCI
5 treated with OMT after failed PCI
11 had incomplete data
346 treated with PCI
(success rate: 90.6%)
29 treated with OMT
36 treated with OMT after failed PCI
6 had incomplete data
1-year FU
348/357 (97.5%)
1-year FU
344/354 (97.2%)
3-year FU
215/231 (93.1%)
3-year FU
218/238 (91.6%)
5-year FU
87/99 (87.9%)
5-year FU
85/102 (83.3%)
19 withdrew consents
In the PCI group only 346 (83 %) treated
with PCI, in the OMT group 310 treated
with OMT (78 %)

8. Study Procedures (2)
•Revascularization for all significant non-CTO
lesions withinavesseldiameterof≥2.5 mm for
patients with multi-vessel coronary artery disease
was recommended.
•Patients were prescribed guideline derived optimal
medical treatment including aspirin, P2Y12
receptor inhibitors (>12months in case of PCI),
beta-blocker, CCB, nitrate, ACEi/ARB, and statin.
•Blood pressure and diabetic control, smoking
cessation, weight control, and regular exercise
were recommended.

9. Baseline Characteristics
OMT (N=398) PCI (N=417) P value
Clinical presentation 0.58
Stable angina 290 (74.9%) 297 (72.3%)
Unstable angina 75 (19.4%) 84 (20.4%)
AMI 22 (5.7%) 30 (7.3%)
Location of CTO 0.71
LAD 161 (41.6%) 183 (44.5%)
LCX 42 (10.9%) 40 (10.2%)
RCA 184 (47.5%) 186 (45.3%)
Multivessel disease 286 (73.9%) 301 (73.3%) 0.76
SYNTAX score 21.0±9.5 21.2±9.1 0.79
J-CTO score 2.3±1.2 2.2±1.2 0.23
Number of total stents 2.0±1.4 2.4±1.3 <0.001
Total stent length, mm 53.6±39.4 71.2±40.5 <0.001
ITT Population

10. Primary End Point
(Death, MI, Stroke, Any Repeat Revascularization)
ITT Population
No. at Risk
OMT 398 305 246 178 129 72
PCI 417 293 241 175 117 65
Y e a rs S in c e R a n d o m iz a tio n
Probability(%)
0 1 2 3 4 5
0
1 0
2 0
3 0
4 0
5 0
6 0
Crude HR 0.95 (95% CI, 0.74-1.22), P=0.67
Adjusted HR 0.91 (95% CI, 0.68-1.23), P=0.54
20.6%
19.6%
25.1%
26.3%
PCI
OMT

11. Quality of Life Measures Over Time
0.0 1.0 6.0 12.0
30
40
50
60
70
80
90
100
6 Mon
303 309
P=0.29P=0.94 P=0.74
Baseline 12 Mon
244 242 231 222
1 Mon
P=0.58
264 277
(A) EQ-5D Visual Analogue Scale
MeanScore
0.0 1.0 6.0 12.0
30
40
50
60
70
80
90
100
305 312
P=0.80P=0.52 P=0.75
243 242 231 221
P=0.05
265 276
(B) SAQ, Physical Limitation
MeanScore
6 MonBaseline 12 Mon1 Mon
6.0 12.0
30
40
50
60
70
80
90
100
304 312
P=0.15P=0.24 P=0.35
244 244 231 222
P=0.17
265 276
(C) SAQ, Angina Stability
MeanScore
6 MonBaseline 12 Mon1 Mon
30
40
50
60
70
80
90
100
304 313
P=0.62P=0.26 P=0.86
244 244 231 222
P=0.001
265 278
(D) SAQ, Angina Frequency
MeanScore
6 MonBaseline 12 Mon1 Mon
30
40
50
60
70
80
90
100
304 313
P=0.96P=0.06 P=0.89
244 244 231 222
P=0.25
265 278
(E) SAQ, Treatment Satisfaction
MeanScore
6 MonBaseline 12 Mon1 Mon
30
40
50
60
70
80
90
100
304 313
P=0.06P=0.28 P=0.90
244 244 231 222
P=0.81
265 278
(F) SAQ, Quality of Life
MeanScore
6 MonBaseline 12 Mon1 Mon
ITT Population

12. A Randomized Multicentre Trial to Evaluate the Utilization
of Revascularization or Optimal Medical Therapy for the
Treatment of Chronic Total Coronary Occlusions
EURO-CTO
NCT01760083

13. Efficacy: Health status @ 12 and 36 months
Safety: Death, non-fatal myocardial infarction (ITT, PP) @ 36 months
Single-vessel disease CTO only
Multivessel CAD including CTO
Treat non-occlusive disease
by PCI before CTO with DES
Angina or
angina-
equivalent
symptoms
Study flow chart
48%
29%

14. Efficacy: Health status @ 12 and 36 months
Safety: Death, non-fatal myocardial infarction (ITT, PP) @ 36 months
Single-vessel disease CTO only
Multivessel 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
Randomization and baseline assessment was
done after all necessary non-CTO PCI !!!

15. 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 only
Multivessel 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

16. PCI procedure in PCI group (n=255)
Radial approach for PCI (%) 34.3
Bilateral approach (%) 81.2
Retrograde approach (%) 35.8
Revascularisation successful (%) 86.3
Stents used
Biomatrix (%) 91.1
Other DES (%) 8.9
Total length of stent used (mm) 65.9 ± 28.9
Width of largest stent (mm) 3.3 ± 2.49
Number of stents used 2.0 ± 1.32
Procedure duration (min) 118.1 ± 67.2
Fluoroscopy time (min) 48.8 ± 34.5

17. 0
10
20
30
40
50
60
70
80
90
100
OMT PCI
Physical
limitation
Anginal
frequency
Anginal
stability
Treatment
satisfaction
Quality of
life
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=0.009
P=0.049
P=0.89
P=0.47

18. Significant change in SAQ subscale scores *)
0
10
20
30
40
50
60
70
80
90
100
Physical
limitation ≥8
Anginal
frequency ≥20
Freedom of
angina (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
Score
Higher score, better health status

19. 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 4
OMT PCI
P<0.001

20. Why are the trial results different ?
EUROCTO DECISION-CTO OPEN-CTO Registry
Figure 3.
Baseline 81 vs 77 83 vs 77 71 failed: 69
FUP 87 vs 92 ∆ 6 vs 15 95 vs 96 ∆ 12 vs 19 92 ∆ 21 84 ∆ 15
0
10
20
30
40
50
60
70
80
90
100
OMT PCI
Physical
limitation
Anginal
frequency
Anginal
stability
Treatment
satisfaction
Quality of
life
r 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=0.009
P=0.049
P=0.89
P=0.47
OMT PCI
ical
ation
Anginal
frequency
Anginal
stability
Treatment
satisfaction
Quality of
life
ng the significance level is 0.01
BL FU BL FU BL FU BL FU BL FU BL FU BL FU BL FU BL FU
022
P=0.009
P=0.049
P=0.89
P=0.47
0.0 1.0 6.0 12.0
30
40
6Mon
303 309
Baseline 12Mon
244 242 231 222
1Mon
264 277
0.0 1.0 6.0 12.0
30
40
305 312 243 242 231 221265 276
6MonBaseline 12Mon1Mon
6.0
30
40
304 312 244 244265 276
6MonBaseline 1Mon
30
40
50
60
70
80
90
100
304 313
P=0.62P=0.26 P=0.86
244 244 231 222
P=0.001
265 278
(D) SAQ, Angina Frequency
MeanScore
6MonBaseline 12Mon1Mon
30
40
50
60
70
80
90
100
304 313
P=0.96P=0.06 P=0.89
244 244 231 222
P=0.25
265 278
(E) SAQ, TreatmentSatisfaction
MeanScore
6MonBaseline 12Mon1Mon
30
40
50
60
70
80
90
100
304 313
P=0.06P=0.28
244 244
P=0.81
265 278
(F) SAQ, QualityofLife
MeanScore
6MonBaseline 1Mon

21. Why are the trial results different ?
0
10
20
30
40
50
60
70
80
90
100
OMT PCI
Physical
limitation
Anginal
frequency
Anginal
stability
Treatment
satisfaction
Quality of
life
or 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=0.009
P=0.049
P=0.89
P=0.47
OMT PCI
inal
ency
Anginal
stability
Treatment
satisfaction
Quality of
life
e level is 0.01
BL FU BL FU BL FU BL FU BL FU BL FU BL FU
09
P=0.049
P=0.89
P=0.47
12.0
12Mon
31 222
0.0 1.0 6.0 12.0
30
40
305 312 243 242 231 221265 276
6MonBaseline 12Mon1Mon
6.0 12.0
30
40
304 312 244 244 231 222265 276
6MonBaseline 12Mon1Mon
P=0.86
231 222
12Mon
30
40
50
60
70
80
90
100
304 313
P=0.96P=0.06 P=0.89
244 244 231 222
P=0.25
265 278
(E) SAQ, TreatmentSatisfaction
MeanScore
6MonBaseline 12Mon1Mon
30
40
50
60
70
80
90
100
304 313
P=0.06P=0.28 P=0.90
244 244 231 222
P=0.81
265 278
(F) SAQ, QualityofLife
MeanScore
6MonBaseline 12Mon1Mon
EUROCTO DECISION-CTO OPEN-CTO Registry
Figure 3.Figure 3.
Baseline 60 vs 55 56 vs 53 50 failed: 51
FUP 72 vs 77 ∆ 12 vs 22 71 vs 70 ∆ 15 vs 17 76 ∆ 26 66 ∆ 15

22. What should be the impact of the EURO CTO trial
• Only EUROCTO assessed the randomized
effect of PCI vs OMT on CTOs with a significant
effect on SAQ scores
• DECISION-CTO is not a conflicting trial, it just
assessed completely different populations and
lesions
• The EURO CTO trial reached its endpoint
despite limited enrolment
• This is a randomized trial that should not be
ignored by guideline committees