1. Clinical Trials and Outcomes with DES in CTO Revascularization
Redefining, Refining Standards of Treatment
David E. Kandzari, MD, FACC, FSCAI
Director, Interventional Cardiology,
Piedmont Heart Institute
Chief Scientific Officer,
Piedmont Healthcare
Atlanta, Georgia

2. Disclosure
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below
Affiliation/Financial Relationship Company
Grant/Research Support Abbott Vascular, Cordis Corporation, Medtronic CardioVascular
Consulting Fees/Honoraria Abbott Vascular, Cordis Corporation, Medtronic CardioVascular, Micell Technologies
Major Stock Shareholder/Equity None
Royalty Income None
Ownership/Founder None
Intellectual Property Rights None
Other Financial Benefit None

3. Evolution of DES as a Standard in CTO Revascularization
Era
Trials
Comparison
Reocclusion %, RR
Restenosis, %, RR
Repeat Revascularization,%, RR
GISSOC, TOSCA, STOP, SPACTO, SICCO
PTCA vs BMS, Randomized
22 vs 9, 59%
67 vs 37, 45%
35 vs 19, 46%
ACROSS, ASIAN, RESEARCH, etc.
DES, Observational 2 8
2006
PRISON II, GISSOC II
BMS vs DES, Randomized
15 vs 2, 87%
52 vs 9, 83%
33 vs 7, 79%
ASIAN, RESEARCH, etc.
PES vs SES, Observational ─
18 vs 7, 61%
6 vs 4, 33%
2010
Metanalyses
BMS vs DES
10 vs 5, 50%
37 vs 10, 73%
30 vs 5, 83%
2011--
PRISON III, CIBELES
SES vs ZES/EES, Randomized
EXPERT CTO, ACE CTO
EES,
Observational

4. Evolution of DES as a Standard in CTO Revascularization
Era
Trials
Comparison
Reocclusion %, RR
Restenosis, %, RR
Repeat Revascularization,%, RR
GISSOC, TOSCA, STOP, SPACTO, SICCO
PTCA vs BMS, Randomized
22 vs 9, 59%
67 vs 37, 45%
35 vs 19, 46%
ACROSS, ASIAN, RESEARCH, etc.
DES, Observational 2 8
2006
PRISON II, GISSOC II
BMS vs DES, Randomized
15 vs 2, 87%
52 vs 9, 83%
33 vs 7, 79%
ASIAN, RESEARCH, etc.
PES vs SES, Observational ─
18 vs 7, 61%
6 vs 4, 33%
2010
Metanalyses
BMS vs DES
10 vs 5, 50%
37 vs 10, 73%
30 vs 5, 83%
2011--
PRISON III, CIBELES
SES vs ZES/EES, Randomized
EXPERT CTO, ACE CTO
EES,
Observational

5. Evolution of DES as a Standard in CTO Revascularization
Era
Trials
Comparison
Reocclusion %, RR
Restenosis, %, RR
Repeat Revascularization,%, RR
GISSOC, TOSCA, STOP, SPACTO, SICCO
PTCA vs BMS, Randomized
22 vs 9, 59%
67 vs 37, 45%
35 vs 19, 46%
ACROSS, ASIAN, RESEARCH, etc.
DES, Observational 2 8
2006
PRISON II, GISSOC II
BMS vs DES, Randomized
15 vs 2, 87%
52 vs 9, 83%
33 vs 7, 79%
ASIAN, RESEARCH, etc.
PES vs SES, Observational ─
18 vs 7, 61%
6 vs 4, 33%
2010
Metanalyses
BMS vs DES
10 vs 5, 50%
37 vs 10, 73%
30 vs 5, 83%
2011--
PRISON III, CIBELES
SES vs ZES/EES, Randomized
EXPERT CTO, ACE CTO
EES,
Observational

6. Evolution of DES as a Standard in CTO Revascularization
Era
Trials
Comparison
Reocclusion %, RR
Restenosis, %, RR
Repeat Revascularization,%, RR
GISSOC, TOSCA, STOP, SPACTO, SICCO
PTCA vs BMS, Randomized
22 vs 9, 59%
67 vs 37, 45%
35 vs 19, 46%
ACROSS, ASIAN, RESEARCH, etc.
DES, Observational 2 8
2006
PRISON II, GISSOC II
BMS vs DES, Randomized
15 vs 2, 87%
52 vs 9, 83%
33 vs 7, 79%
ASIAN, RESEARCH, etc.
PES vs SES, Observational ─
18 vs 7, 61%
6 vs 4, 33%
2010
Metanalyses
BMS vs DES
10 vs 5, 50%
37 vs 10, 73%
30 vs 5, 83%
2011--
PRISON III, CIBELES
SES vs ZES/EES, Randomized
EXPERT CTO, ACE CTO
EES,
Observational

7. Evolution of DES as a Standard in CTO Revascularization
Era
Trials
Comparison
Reocclusion %, RR
Restenosis, %, RR
Repeat Revascularization,%, RR
GISSOC, TOSCA, STOP, SPACTO, SICCO
PTCA vs BMS, Randomized
22 vs 9, 59%
67 vs 37, 45%
35 vs 19, 46%
ACROSS, ASIAN, RESEARCH, etc.
DES, Observational 2 8
2006
PRISON II, GISSOC II
BMS vs DES, Randomized
15 vs 2, 87%
52 vs 9, 83%
33 vs 7, 79%
ASIAN, RESEARCH, etc.
PES vs SES, Observational ─
18 vs 7, 61%
6 vs 4, 33%
2010
Metanalyses
BMS vs DES
10 vs 5, 50%
37 vs 10, 73%
30 vs 5, 83%
2011--
PRISON III, CIBELES
SES vs ZES/EES, Randomized
EXPERT CTO, ACE CTO
EES,
Observational

8. Evolution of DES as a Standard in CTO Revascularization
Era
Trials
Comparison
Reocclusion %, RR
Restenosis, %, RR
Repeat Revascularization,%, RR
GISSOC, TOSCA, STOP, SPACTO, SICCO
PTCA vs BMS, Randomized
22 vs 9, 59%
67 vs 37, 45%
35 vs 19, 46%
ACROSS, ASIAN, RESEARCH, etc.
DES, Observational 2 8
2006
PRISON II, GISSOC II
BMS vs DES, Randomized
15 vs 2, 87%
52 vs 9, 83%
33 vs 7, 79%
ASIAN, RESEARCH, etc.
PES vs SES, Observational ─
18 vs 7, 61%
6 vs 4, 33%
2010
Metanalyses
BMS vs DES
10 vs 5, 50%
37 vs 10, 73%
30 vs 5, 83%
2011--
PRISON III, CIBELES
SES vs ZES/EES, Randomized
EXPERT CTO, ACE CTO
EES,
Observational

9. DES in CTO Revascularization Quantifying the Relative Benefit of DES: ≥3 Year Follow-up
64% RR
62% RR
Saeed, Kandzari, Brilakis et al. CCI 2010

10. DES in CTO Revascularization Quantifying the Relative Benefit of DES: ≥3 Year Follow-up
Saeed, Kandzari, Brilakis et al. CCI 2010

11. CTO Revascularization and Late Safety and Efficacy 3 Year Outcomes ACROSS/TOSCA 4
∆1-3 Yrs
3 Years
Death
2.6
2.6% MI
1.0%
3.2
4.2%
TLR
9.8%
1.1
10.9%
Stent Thrombosis*
MACE
10.3%
4.8%
15.1%
Kandzari. *ARC def/probable ST

12. CTO Revascularization and Late Safety and Efficacy 5 Year Outcomes PRISON II41
P=0.009
P<0.001 36
P=0.001 34 30
Event (%) 17 17
P=NS
P=NS 12 12 8 7 5 5
Suttorp. TCT 2010

13. CTO Revascularization and Late Safety and Efficacy 5 Year ARC Definite/Probable Stent Thrombosis
BMS, N=100
SES, N=100
Index-30 days
1 (d)
31 days to 1 year
1-2 years
2-3 years
2 (d)
3-4 years
2 (1d, 1p)
4-5 years
Total 1 8
P=NS for all comparisons
Suttorp. TCT 2010

14. DES Trials in CTO Revascularization
Design
Primary Endpoint
Timeline
CIBELES NCT
208
Randomized,
Xiencevs. Cypher
9 month in-stent late loss, non-inferiority
PCR 2011
PRISON III NCT
300
Randomized, Cypher vs. Endeavor, Resolute
8 month in-segment late loss
ACC 2011
ACE CTO NCT
100
Single-arm,XienceV
8 month binary restenosis, OCT
TCT 2012
EXPERT CTO NCT Pending
250
Single-arm,Xience V
1 year MACE vs. DES performance goal
2° Endpoints: 1.2 Mini Trek, Progress Guidewires
Enrollment 2011

15. 85% adjusted relative reduction
ACROSS - CYPHER
Influence of Stent Technique on Angiographic Outcomes
In treated-segment refers to length of contiguous target segment exposed to balloon inflation
In-segment includes stented area plus 5 mm proximal and distal to stent
Restenosis is more common in the treated (but not stented) segment than in-stent!
33% absolute reduction
85% adjusted relative reduction
∆working- stent11.1%
∆working- segment10.2%
Binary Restenosis (%)
∆segment- stent2.9%
Kandzari et al. JACC Interv 2009

16. Influence of Stent Technique on Angiographic Outcomes DES, Hybrid, BMS
56.7
55.0
53.4
33.3
33.3
23.8
21.7
13.3
11.7
9.3
10.0
1.7
Werner et al. CCI 2006

17. Stent Fracture Following CTO Revascularization

18. Stent Fracture Following CTO Revascularization

19. Non-stent Fracture (N=168)
Stent Fracture Following CTO Revascularization
Correlates and Outcomes
Stent Fracture (N=32)
Non-stent Fracture (N=168)
P value
Stent length, mm
65.5 (49.7, 73.6)
41.9 (28.8,57.0)
<0.001
Overlapping stents (%)
100 (30/30)
89.9 (107/119)
0.06
Procedure success (%)
(32/32)
97.6 (163/167)
1.00
Target lesion revascularization (%)
25.0 (8/32)
6.7 (11/162)
0.005
Major adverse cardiac events (%)
7.4 (12/161)
0.007
Stent thrombosis (%)
3.2 (1/31)
0.6 (1/162)
0.30
Binary restenosis (%)
In-segment
9.5 (13/137)
0.017
In-stent
15.6 (5/32)
8.0 (11/137)
0.17
Kandzari et al. JACC Interv 2009

20. Late Incomplete Apposition and Aneurysm Formation
CTO an independent predictor of aneurysm formation
Jim et al. Circ J 2011
IVUS identified in  26%~ of CTO cases at follow-up
Hong et al. Circulation 2006
Association with VLST
Miyazaki J Invasive Cardiol2010

21. Late Incomplete Apposition and Aneurysm Formation Baseline, Acquired, Persistent, Resolved

22. Late Incomplete Apposition and Aneurysm Formation

23. Late Incomplete Apposition and Aneurysm Formation
2 Months
5 Months

24. Late Incomplete Apposition and Aneurysm Formation Opportunity for Healing?
Baseline
2 Months
5 Months

25. DES in CTO Revascularization Summary
PCI with DES in CTO revascularization is a standard of care rather than an exception, often to the extent that ineligibility for DES challenges considerations for attempting CTO
Substantial reductions in restenosis and repeat revascularization
Similar safety compared with BMS
Aside from ↓ABR, long term patency with DES may be associated with preservation of improved LV function
DES are a revolutionary step toward improving CTO outcomes but introduce new dilemmas
Implications for technique: ↑ restenosis when less DES coverage
Strut fracture and LSM may be more common; clinical implications uncertain
CTOs represent ideal opportunity to evaluate DES safety and efficacy in the highest lesion complexity
Outstanding need for comparative trial of DES (esp. new DES), clinical outcomes and impact of new technologies/techniques