Eberhard-Karls Karls-University of Tubingen Department of Diagnostic Radiology Neuestes aus der Therapie der pavk Berlin Dezember 08 beschichtete Stents + Ballons Gunnar Tepe 1
Local Drug Delivery Basic Principles To be modified Stent based A Stent design (homogenoius delivery) Delivery kinetic Coating/Adsorption Drug Short time contact B Mode of delivery (with a balloon, fluid) Adjuncts Drug 2
A1 DES in the AFS SIROCCO Study Design blinded, randomized, prospektiv 36 patients (Sirocco I) + 57 patients (Sirocco II) primary endpoint: Restenosis in stent after 6 months 3 Duda et al.: Circulation. 2002; 106: 1505-1509 Tepe et al: J Cardiovasc Surg. 2005; 46: 249-259 Duda et al: J Endovasc Ther. 2006; 13: 701-710
A1 SIROCCO II Restenosis Rate 6m 9m 18m 24m 36m 48m Sirolimus Restenosis Rate 3.8% (1/26) 7.7% (2/26) 15.4% (4/26) 29.2% (7/24) 31.8% (7/22) 42.1% (8/19) Bare metal Restenosis Rate 0% (0/26) 11.5% (3/26) 20.0% (5/25) 20.0% (5/25) 33.3% (7/21) 41.2% (7/17) Total Restenosis Rate 1.9% (1/52) 9.6% (5/52) 17.6% (9/51) 24.5% (12/49) 32.6% (14/43) 41.7% (15/36) 4
More Drug Eluting Stent Trials A2 Zilver PTX Trial (Cook Inc.) a.ptx adsorbed b.studies: 1000 patients Prim. Endpoints USA: 240 patients Stent vs. PTA Europe: 760 patients (Safety DES) 12 months effictiveness Freedom from TLR a. Interv.: Reststenosis >30% b. Clin. driven Reintervention 12 months safety 6 months event-free survival a. serious adverse event, b. worsening Rutherford by 2 classes 5
A2 Lesion Characteristics Characteristic Randomized Study (Phase 1) Registry Study PTA ZPTX ZPTX Number of lesions 33 29 91 TASC class: A 13 (39%) 13 (45%) 12 (13%) B 9 (27%) 3 (10%) 26 (29%) C 6 (18%) 9 (31%) 36 (40%) D 1 (3%) 1 (3%) 17 (19%) Calcification 23 (70%) 24 (83%) 66 (72%) Total occlusion 5 (15%) 4 (14%) 37 (40%) In-stent restenosis 0 (0%) 0 (0%) 24 (26%) Other stenosis in artery > 50% 1 (3%) 6 (21%) 22 (24%) Average stents per lesion 1.0 1.0 2.2 6
A2 Baseline Angiographic Data Randomized Study (Phase 1) Registry Study PTA (N = 33 lesions) ZPTX (N = 29 lesions) ZPTX (N = 91 lesions) Lesion Length (cm) 3.6 ± 2.0 (range 1 to 7) 4.1± 3.1 (range 1 to 10) 10 ± 8.1 (range 1 to 33) Proximal RVD (mm) 5.2 ± 1.0 5.0 ± 1.1 5.3 ± 0.8 Distal RVD (mm) 5.3 ± 1.0 4.9 ± 1.1 5.1 ± 0.8 MLD in lesion (mm) 1.3 ± 0.8 1.1 ± 0.7 0.6 ± 0.7 % Diameter Stenosis 76 ± 15 78 ± 14 89 ± 12 7
A2 6-Month Effectiveness Study Freedom from TLR Randomized Study (Phase 1) PTA Group 52% (17/33 lesions) No PTA failure 100% (17/17) Acute PTA failure Bare Zilver 75% (6/8) Acute PTA failure Zilver PTX 100% (8/8) ZPTX Group Registry Study 90% (26/29 lesions) 90% (82/91 lesions) 8
A2 Registry Study Effectiveness Registry Study Subgroup TASC A and B TASC C and D De novo Restenotic In-stent Restenosis Freedom from TLR 92% (of 38 lesions) 89% (of 53 lesions) 91% (of 57 lesions) 88% (of 34 lesions) 92% (of 24 lesions) < 7cm lesions 91% (of 43 lesions) > 7 cm lesions 90% (of 48 lesions) Overall 90% (of 91 lesions) 9
A3 More Drug Eluting Stent Trials Strides Trial (Abbott Vascular) a.everolimus coating b.study: 100 patients Clinical Duplex Ultrasound Angiography 30d 6mo 12mo 18mo 2yr 3yr 4yr 5yr 10
Short time local drug contact: the alternative approach 11
DES vs. Short Time Drug Contact DES dramatically improve interventional cardiology Potential disadvantages DES require stent implantation Long-term effects of the polymeric matrix Drug concentration is highest at the stent struts where healing is most important SFA: stent fractures? SIROCCO? Do we need sustained drug release? 12
Thunder trial study design Control n=54 PAD n=154 + Iopromid- Paclitaxel * n=52 +Paclitaxel Balloon ** n=48 Design - prospective - randomized - blinded - multi-center 6-months Control Decision according further follow-up If difference between two groups 15% * ~17 mg Paclitaxel/100 ml KM ** ~ 3µg/mm 2 Paclitaxel 12-months Control 13
Inclusion criteria Occlusion or stenosis > 2 cm (mean grade of stenosis > 70%) SFA, APOP History > 6 weeks (no thrombolysis) Successful guide wire passage Rutherford 1-5 Age: 18-95 years Informed consent, agreement for f/u 14
Exclusion criteria Distal run-off less than one artery Known allergy: Aspirin, Clopidogrel, Heparin, Paclitaxel, Contrast media Creatinine > 2.0 mg% PTA directly at the proximal origin of the SFA 15
Primary endpoint Late Lumen Loss (LLL) Quantitative Angiography MLD RVD (prox) Minimal Lumen Diameter = MLD RVD (distal) Reference Vessel Diameter (RVD) = average of vessel diameter proximal and distal to the lesion Percent Diameter Stenosis (%DS) = ratio of MLD to RVD MLD RVD 16
Patient characteristics Characteristics Uncoated BA n = 54 Uncoated BA + Paclitaxel i.a. n = 52 Paccocath n = 48 Mean age 68 ± 9 68 ± 8 69 ± 8 Gender m/f 1.8 2.3 1.8 Smoker [%] 22 27 23 Diabetes [%] 46 52 50 Hypertension [%] 83 87 79 Hypercholesteremia [%] 63 65 69 17
Lesion characteristics Characteristics Lesion lengths [cm] pre-procedure Uncoated BA n = 54 Uncoated BA + Paclitaxel i.a. n = 52 Paccocath n = 48 7.4 ± 6.7 7.4 ± 6.5 7.5 ± 6.2 Mean degree of stenosis [%] 91 88 89 Occlusion [%] 26 27 27 Mean number of lesions treated 1.6 1.7 1.8 De-novo lesion [%] 70 58 62 18
Cumulative MLD at month 6 Paccocath 100% CumProb 75% 50% 25% MLD_pre MLD_post MLD_6M 0% -1 0 1 2 3 4 5 6 7 8 MLD [mm] 100% Uncoated BA P < 0.01 CumProb 75% 50% MLD_pre MLD_post MLD_6M 25% 19 0% -1 0 1 2 3 4 5 6 7 8 MLD [mm]
Late lumen loss at month 6* Mean P = < 0.01 [mm] 4,0 n=48 n=39 n=41 3,0 2,0 1,0 0,0 Uncoated BA Uncoated BA / Paclitaxel i. a Paccocath * for available patients Treatment group 20 Wilcoxon test
Target lesion revascularization* [%] 70 60 6 month 12 month 50 40 30 20 10 0 Uncoated BA Uncoated BA / Paclitaxel i.a Paccocath BA = Balloon angioplasty * Including 12 months re-intervention 21
Disposition of patients at month 12 Reasons for not having a 12 month follow up Randomization according to inclusion/exclusion criteria n = 154 Uncoated BA Baseline n = 54 6-mo clinical FU n=50 Angiography n = 48 (89%) N Death = 2 N Amputation = 0 Uncoated BA + Paclitaxel i. a., n = 52 6-mo clinical FU n=41 Angiography FU n = 39 (75%) N Death = 3 N Amputation = 2 Paccocath Baseline n = 48 6-mo clinical FU n=43 Angiography FU n = 41 (85%) N Death = 2 N Amputation = 1 N TLR/drop out = 4 N TLR/drop out = 3 N TLR/drop out = 0 N Lost to follow up = 1 N Lost to follow up = 0 N Lost to follow up = 0 N Other = 5 N Other = 6 N Other = 5 1-yr clinical FU n=42* Angiography n = 36 (67 %) 1-yr clinical FU n=38* Angiography n = 29 (56 %) 1-yr clinical FU n=40* Angiography n = 33 (69 %) * Including patients with telephone contact 22
Primary Endpoint: Late Lumen Loss* [mm] P < 0.01 5 4 3 6 month 12 month 2 1 0 Uncoated BA Uncoated BA / Paclitaxel i.a Paccocath BA = Balloon angioplasty * Available patients 23
Late lumen loss in patients WITHOUT previous TLR [mm] 5 4 n=45 n=22 n=37 n=20 n=41 N=31 6 month 3 12 month 2 1 0 Uncoated BA Uncoated BA / Paclitaxel i.a Paccocath BA = Balloon angioplasty 24
Binary Restenosis Rate % of patients reaching 50% stenosis in target lesion after initial PTA [%] 70 60 6 month 12 month 50 40 30 20 10 0 Uncoated BA Uncoated BA / Paclitaxel i.a Paccocath BA = Balloon angioplasty 25
Patient treated with Paccocath 26
* Pre intervention Post intervention 27
Post intervention 28 Post intervention 6 months 12 months
Conclusions On DES Currently NO data that DES in the SFA work 2 ongoing trials With ((D)ES?) high risk lesions treated effectively On short time contact with PTX DEB safe and effective Sustainded results after 12 months Local delivery with CM does not work 29