CTO - PCI

IMI 0 . : TIMI 1 ,

12 12 3 . 1

. .

Prevalence of Total Occlusion(s) in Coronary Patients

30%

70%

Patients with Total Occlusions Patients without Total Occlusions

30% of patients have one or more total occlusions

Source: Cardiac Data Resources, The BLG Group

Total Occlusion;Pathophysiology
Bidirectional thrombus formation ends first

Gradual replacement of thrombus, cholesterol IP with collagen, calcium

Fibrous tissue density greatest at prox and distal ends (caps)

Suzuki et al. AJC 2001 Srivatsa et al. JACC 1997 Abbate et a. Circulation 2002

CTO ?
: 1. 2. 3. . - .

Rationale for Opening CTOs

Outcomes
Improvement in left ventricular ejection fraction and wall motion after successful recanalization of chronic coronary occlusions
Sirnes PA; et. al., European Heart Journal, 19(2): 273-81 1998 February

95 patients with recanalized CTO (71% stents) Left ventriculogram at baseline and 6.7 month follow-up LVEF increased from 0.62 to 0.67 (p=.001) 8 patients with reocclusion unchanged (p = .04) Regional radial shortening in area of recanalized artery increased by 16% (p = .001) and was unchanged in patients with reocclusion Possible recovery of hibernating myocardium

Rationale for Opening CTOs

Outcomes
Initial and Long term outcome of 354 patients after PTCA of CTOs
Bell MR; Holmes DR; et. Al. Circ 1992; 85; 1003-11 Clin Investig, 72 (6): 442-7 1994 Jun

At 5 years, freedom from death, MI, CABG, was 52% in successful vs 17% failed PTCAs (p<.001) Successful PTCA was most significant predictor of freedom from CABG

Rationale for Opening CTOs

Survival Outcomes
Natural History of Single Vessel Disease Trappe et. Al.; European Heart Journal 1989; 10; 514514-24 48 month follow up - 15% incidence of sudden death in patients with CTO, compared to 3% in patients with coronary stenosis

Rationale for Opening CTOs Survival Outcomes

  

Moliterno et. al. Ivanhoe RJ et. al. Bell MR et. al.

1992 1992 1992

Coronary Artery Disease Circulation Circulation

All studies report improved survival in patients with successful PTCA of CTO compared to patients with failed PTCA for CTO

PCI CTO 1. success PTCA vs failure PTCA 2. PTCA vs BMS. 3. BMS vs DES.

1 Study of the Italian Society of Cardiology TOAST-GISE) 286 TOAST(British Columbia Cardiaoc Regystry 1118 340 (Mid American Heart Instiute , Kansas City 1491 (Mid 83 514

(Total Occlosion Angioplasty (Total ;6 10 .

35 30 25 20 15 10 5 0 1 6 10 success failure

Stents in Total Occlusion for restenosis Prevention The multicentre randomized STOP study


: . . CTO. 59+; 10.3 59+; , ( 1818-39 ). . 69 7 % . ( P= 0.034). . 6 PTCA 7 . 42 % 16 % . 15 .

: 49 52

96

: CTO. CTO.

The Total Occlusion Study of Canada (TOSCA)

BackgroundBalloon angioplasty (PTCA) of occluded coronary arteries is limited by high rates of restenosis and reocclusion. Although stenting improves results in anatomically simple occlusions, its effect on patency and clinical outcome in a broadly selected population with occluded coronary arteries is unknown. Methods and ResultsEighteen centers randomized 410 patients with nonacute native coronary occlusions to PTCA or primary stenting with the heparin-coated Palmaz-Schatz stent. The primary end point, failure of sustained patency, Was determined at 6-month angiography. Repeat target-vessel revascularization, adverse cardiovascular events, and angiographic restenosis (.50% diameter stenosis) constituted secondary end points. Sixty percent of patients had occlusions of .6 weeks duration, baseline flow was TIMI grade 0 in 64%, and median treated segment length was 30.5 mm. With 95.6% angiographic follow-up, primary stenting resulted in a 44% reduction in failed patency (10.9% versus 19.5%, P50.024) and a 45% reduction in clinically driven target-vessel revascularization at 6 months (15.4% versus 8.4%, P50.03). The incidence of adverse cardiovascular events was similar for both strategies (PTCA, 23.6%; stent, 23.3%; P5NS). Stenting resulted in a larger mean 6-month minimum lumen dimension (1.48 versus 1.23 mm, P,0.01) and a reduced binary restenosis rate (55% versus 70%, P,0.01). ConclusionsPrimary stenting of broadly selected nonacute coronary occlusions is superior to PTCA alone, Impruving late patency and reducing restenosis and target-vessel revascularization. (Circulation. 1999;100:236-242.)

Baseline Clinical Characteristics

               

TABLE 1. Baseline Clinical Characteristics Characteristic PTCA (N208) Stent (N202) P Age, y 57.7+-10.6 57.6+-10.4 NS Male 167 (80) 169 (84) NS CCS angina class II-III 117 (56) 122 (60) NS CCS angina class IV 51 (25) 49 (24) NS Prior MI 139 (67) 136 (67) NS MI within 6 wk 59 (28) 65 (32) NS Ejection fraction, % (mean6SEM) 60+-12 60+-11 NS Prior congestive heart failure 8 (4) 7 (4) NS Prior PTCA 27 (13) 25 (12) NS Prior CABG 3 (1) 3 (2) NS Diabetes 38 (18) 30 (15) NS Hypertension 89 (43) 70 (35) NS Active smoker 41 (20) 36 (18) NS Prior stroke/transient ischemic attack 9 (4) 4 (2) NS

PCI Treatment of CTO

 Historically,

lower primary success rates

 High


restenosis rates

PTCA: up to 75%  Stent: 20% to 35%

 Increased


procedure time and costs

40% higher in Mayo Clinic Study

CTO: Restenosis Rates for BMS

55%

60 %

42%

50 %

32%

32%

0%

10 %

20 %

30 %

40 %

TO SC

G IS SO

ST O

SI C

CO

What Is The Evidence For The Use Of DES In CTO

       

RESEARCH & T-SEARCH Registry TSICTO Registry WISDOM Registry E-Cypher Registry Asian Registry PRISON II CORACTO ACROSS Cypher

What Is The Evidence For The Use Of DES In CTO

       

RESEARCH & T-SEARCH Registry TSICTO Registry WISDOM Registry E-Cypher Registry Asian Registry PRISON II CORACTO ACROSS Cypher

RESEARCH and T-SEARCH Registries TLesion Characteristics

Bare Metal
Occlusion length Reference diameter* diameter* Number of stents* stents* Total stent length* length* N=26 13.0 7.2 2.34 0.43 1.8 0.8 41.5 23.3

Sirolimus
N=76 10.3 5.9 2.35 0.51 2.2 1.2 48.8 27.4

Paclitaxel
N=58 11.2 6.6 2.60 0.49 2.6 1.3 58.0 32.8

*P<0.05; Hoye, Serruys et al. 2004

CTO: Research Registry

Thirty Three Patients with CTO > 1Mo duration Outcomes


Restenosis

(6 mo)

9%

12 Month Follow up  Death  AMI  TLR  MACE free survival

0% 0% 6.1% 96.4%

Serruys ACC 2004

RESEARCH and T-SEARCH Registries

100 Cumulative Survival-free of TVR (%)

95

SES: 97.4%, N=76 PES: 96.4%, N=57

90

85

Log rank p=0.01

80

BMS: 80.8%, N=26

75 0 6 Follow-up (months) 12 Hoye, Serruys et al. 2004

What Is The Evidence For The Use Of DES In CTO

       

RESEARCH & T-SEARCH Registry TSICTO Registry WISDOM Registry E-Cypher Registry Asian Registry PRISON II CORACTO ACROSS Cypher

SIROLIMUS-ELUTING STENT ROLIMUSIN CHRONIC TOTAL OCCLUSION

The SICTO Study


Study Design


A multicenter, prospective, non-randomized study of coronary non stenting with the Cypher sirolimus-eluting stent in patients with sirolimuschronic total occlusion 25 Pts were treated with the Cypher stent after successful balloon angioplasty and IVUS examination Clinical follow-up at 30 days; 6, 12, 18, and 24 months; repeat followangiography and IVUS at 6-month follow-up 6followLotan et al EuroPCR 2004

SICTO: IVUS Data 6-Month Follow-Up FollowIVUS post Mean stent area Mean lumen area Minimum lumen area % stent plaque volume 8.6 1.8 8.6 1.8 6.7 1.7 NA IVUS f/u 8.7 1.7 8.3 1.9 6.4 2.2 13.1 18.3

SICTO Study:
6 Month Events
6 months 0 0 0 0 0 2 (8%) 0

MACE (overall) Death MI Emergency CABG Target lesion PTCA TVR* Acute/Subacute thrombosis

* 1 patient proximal + distal stenosis outside stent 1 patient distal dissection at index procedure, treated at follow-up

What Is The Evidence For The Use Of DES In CTO

       

RESEARCH & T-SEARCH Registry TSICTO Registry WISDOM Registry E-Cypher Registry Asian Registry PRISON II CORACTO ACROSS Cypher

e-Cypher Outcomes in CTO Patients

10 8 Incidence % 6 4 2 0
Composite Cardiac Death MI TVR
0,24 1,06 3,1 1,11 0 0,27 1,39 0,53 0,24

N=360 pts
Procedure One Month Six Months

0 0,27

0,56

e-Cypher 6 month event rate:

CTO subset (n=360) vs Others (n=10962)
10 8 Incidence % 6 4 2 0
Composite Cardiac Death MI TVR
3 3,1 1,42 0,92 1,11 1,39 1,06 Overall CTO

0,56

What Is The Evidence For The Use Of DES In CTO

       

RESEARCH & T-SEARCH Registry TSICTO Registry WISDOM Registry E-Cypher Registry Asian Registry PRISON II CORACTO ACROSS Cypher

WISDOM Registry
9 Countries with Early Market Approval 22 Active Sites (778 pts) Primary Endpoint 12-month outcome of real world 12interventions using the paclitaxel-eluting TAXUSSR Express paclitaxelstent in high-risk patient and lesion subgroups high    

Diabetics Patients with ACS Total occlusions Longr lesions Smaller vessels 10.0%
Abazaid et al 2005

33.4% 18.3% 8.4% 15.2%

Impact of CTO at 12 months

15
Overall n=778 CTO n= 65

Incidence %

10 5,2 5 2,2 %1,7% 0 Composite Cardiac Death 1,3% 6,7% %

3,3% 2% 1,7%

MI

TVR

What Is The Evidence For The Use Of DES In CTO

       

RESEARCH & T-SEARCH Registry TSICTO Registyr WISDOM Registry E-Cypher Registry Asian Registry PRISON II CORACTO ACROSS Cypher

ASIAN Registry
Five Center Asian Registry Eighty Eight Patients with 102 CTO lesions Treated with Cyphertm stent
Procedural Success  Mace (30 Days)  6-Month Outcomes


100% 0%
3.4% 4.5% 4.5%

Restenosis  TVR  MACE



Nakamura et al ACC 2004

What Is The Evidence For The Use Of DES In CTO

       

RESEARCH & T-SEARCH Registry TSICTO Registry WISDOM Registry E-Cypher Registry Asian Registry PRISON II CORACTO ACROSS Cypher

Sirolimus-Eluting and Bare Metal Stents in irolimuscclusion Patients With Chronic Total Occlusions Chronic PRISON II
SingleSingle-blind study (n=200) with coronary artery CTO were randomised to either CYPHER or the Bx Velocity(BMS) Coronary artery CTO > 2 weeks with signs of ischemia related to the target vessel. Exclusion included failure to cross lesion

PRISON II:
Clinical And Angiographic Outcomes
BareBaremetal stent MACE* (%) 20 TVF** (%) 24 % diameter stenosis, in-stent in48.75 % diameter stenosis, in-segment in53.32 Late loss, in-stent (mm) in1.09 Late loss, in-segment (mm) in0.64 Binary restenosis (in-stent) (%) (in41 Binary restenosis (in-segment) (%) 36 (inReocclusions (%) 13 End point Cypher p 4 8 22.01 31.85 0.05 -0.07 11 7 4 <0.001 0.003 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.001 <0.04

*MACE=cardiac death, MI, ischemia-driven TLR **A composite of cardiac death, MI, ischemia-driven revascularization of the target vessel

Suttorp M. TCT 2005; October 16-21, 2005; Washington, DC.

What Is The Evidence For The Use Of DES In CTO

       

RESEARCH & T-SEARCH Registry TSICTO Registry WISDOM Registry E-Cypher Registry Asian Registry PRISON II CORACTO ACROSS Cypher

Constant Constant Stent (Neich) With Rapamycine Rapamycine In Chronic Total Occlusions: CORACTO
Bad Soden/Trier Principle Investiagator: Primary Endpoint: 100 pts Randomized to DES VS BMS N. Reifart

6 months angiographic late loss and restenosis

Secondary Endpoint: TLR for clinical symptoms or >70% angiographic stenosis Clinical Follow-up at One Year Follow-

CORACTO Trial (Interim Analysis 44 pts, 124 stents)

80 70 60
Incidence %

60% 49%

50 40 30 20 10 0 >50% Restenosis
N=15 N=5

21% 5,2%

TVR

What Is The Evidence For The Use Of DES In CTO

       

RESEARCH & T-SEARCH Registry TSICTO Registyr WISDOM Registry E-Cypher Registry Asian Registry PRISON II CORACTO ACROSS Cypher

Approaches to ChRonic Occlusions With Sirolimus Ch Stents : ACROSSACROSS-CypherTM/Total Occlusion Study of Coronary novo total coronary occlusions 250 patients with deArteries (TOSCA 4)
17 sites within North America Single-arm trial design
Clinical Follow-up Follow30 d Angiographic Follow-up Follow6 mo 12 mo 2 yr 3 yr 4 yr 5 yr

Primary Endpoints: Secondary Endpoints: Stent Sizes: Antiplatelet therapy:

Angiographic restenosis at 6 months compared with TOSCA-1 Angiographic in-segment restenosis at 6 months; TVF, MACE and TLR at 6 and 12 months; late loss at 6 months Cordis CypherTM 2.5-3.5 mm x 8-33 mm Pre- and post-dilatation specified; balloon length < stent length 3 months

55%

42%

32% 32%

9% 8%

CTO: Restenosis Rates for BMS

10 20 30 40 50 60 T 0 O % % % % % % % S C A S TO P G IS S O C S R IC E C S O E A R C H S I C CT A O R A C T P O R IS O N I A I S I W AN IS D O M
5,2% 4,0% 4,5% 1,7%

Conclusions: Treatment of CTO with DES



The treatment of CTO with DES ( Sirolimus or Paclitaxel) is safe

The long term patency is high (>90%) and is approaching non-CTO stenosis. non-

Low rates of acute and sub-acute thrombosis despite sublesion and patient complexity