drug delivery devices for btk treatment · fmrp 2016 | 1 linc ap 2016, hong kong drug delivery...
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FMRP 2016 | 1
LINC AP 2016, Hong Kong
Drug delivery devices for BTK treatment
Koen Deloose , MD
Marc Bosiers Koen Deloose Joren Callaert
A.Z. Sint-Blasius, Dendermonde
Patrick Peeters Jürgen Verbist
W. Van den Eynde
OLV Hospital, Aalst
Lieven Maene Roel Beelen
R.Z. Heilig Hart, Tienen
Koen Keirse Bart Joos
Imelda Hospital, Bonheiden
FMRP 2016 |
Disclosure slide
I have the following potential conflicts of interest to report:
Consulting
Employment in industry
Stockholder of a healthcare company
Owner of a healthcare company
Other(s)
I do not have any potential conflict of interest
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BTK vessels are @risk for restenotic cascade
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Drug elution is the only solution…
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•Crush plaque •Stretch artery • De-endothelialization
•Platelet/fibrin deposition
Signaling
cascades
•SMC migration & division •ECM
production •Re-endotheliazation
RESTENOSIS
Antiproliferative Agents
FMRP 2016 |
Drug elution is the only solution
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Taxol Family Limus Family
Paclitaxel Siro-limus
Evero-limus
Zotaro-limus
Tacro-limus
DES DCB
Cook
Medical Boston
Scientific Stentys
Medtronic
Bard
Biotronik
Spectranetics
Ivascular
Cardionovum
EuroCor
Boston
Scientific
Cook Medical
Cordis Abbott Medtronic Sorin
Biomedica
FMRP 2016 |
DES – BTK in literature…
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0 5 10 15 20 25 30 35 40 45 50 55 60
100
90
80
70
60
50
40
30
20
10
0
Time (months)
DES-registry
Primary Patency
DES-RCT
31mm 27mm 21mm
Rastan A. et al (2011). European Heart Journal, 32, 2274-2281 ; Bosiers M. et al (2012). Journal of Vascular Surgery, 55, 390-398
Scheinert D. et al (2012). Journal of the American College of Cardiology, 60, 2290
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• Prospective, non-randomized, multi-center study
(3 Belgian, 2 German centers) : 70 patients
• Study objective:
To evaluate the immediate and long-term (up to 12 months) outcome of the PROMUS ELEMENT (PLUS) Everolimus-Eluting Coronary Stent System (Boston Scientific) in a corelab controlled prospective way for BTK lesions of max 40mm
PREVENT study
DES – BTK in literature…
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DES – BTK in literature…
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Baseline 1MFU 6MFU
Freedom from TLR (%) 100 100 96.8
Patients at risk 70 68 59
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96.8 %
Baseline 1MFU 6MFU
Primary Patency (%) 100 100 95.4
Patients at risk 70 68 59
95.4 %
Baseline 1MFU 6MFU
Freedom amputation (%) 100 100 100
Patients at risk 70 68 59
100.0 %
DES – BTK in literature…
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• Prospective, non-randomized, multi-center study
(4 Belgian, 3 German, 1 Australian center)
• Study objective:
To evaluate the immediate and long-term (up to 12 months) outcome of the XIENCE PRIME BX Everolimus-Eluting Coronary Stent System (Abbott Vascular) in a corelab controlled prospective way for BTK lesions between 30mm and 100mm
DESTINY 2 study
DES – BTK in literature…
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DES – BTK in literature…
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75.4 %
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84.9 %
time baseline 1MFU 6MFU 12MFU
at risk 60 58 50 42
% 100 100 94.5 84.9
time baseline 1MFU 6MFU 12MFU
at risk 60 57 43 37 % 100 98.3 83.4 75.4
96.6 %
time baseline 1MFU 6MFU 12MFU
at risk 60 57 52 49
% 100 96.6 96.6 96.6
DES – BTK in literature…
FMRP 2016 |
PES BTK-70 study
Prospective, non-randomized, multi-center study ( 5 belgian centers)
To evaluate the immediate and long-term (up to 12 months) outcome of the dedicated BTK SX Paclitaxel-Eluting Stentys Stent System (Stentys) in a corelab controlled prospective way for BTK lesions of max 50 mm
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DES – BTK in literature…
FMRP 2016 | 14
DES – BTK in literature…
FMRP 2016 |
time baseline 6MFU 12MFU
at risk 70 55 46 % 100 89.2 79.1
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79.1 %
DES – BTK in literature…
time baseline 6MFU 12MFU
at risk 70 54 43
% 100 87.6 72.6
72.6%
time baseline 6MFU 12MFU
at risk 70 62 55
% 100 98.5 98.5
98.5 %
FMRP 2016 | 16 Fusaro M, JACC 2013;6:1284-93
DES – BTK in literature…
FMRP 2016 | 17
DES – BTK in literature…
Fusaro M, JACC 2013;6:1284-93
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DES – BTK in literature…
Fusaro M, JACC 2013;6:1284-93
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• Coronary DES trials showed increased risk for restenosis if full index lesion is not completely covered by DES
Sakurai et al. Am J Cardiol 2005;96:1251–1253.
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DCB-BTK Evidence: The LEIPZIG Registry
Single Center Registry • 104 Patients (CLI 82.6%) • Diabetes 73% • Mean lesion length 17 cm • CTO’s 62%
IN.PACT Amphirion* vs. matched PTA historical cohort**
* Schmidt A et al. J Am Coll Cardiol. 2011 Sep 6;58(11):1105-9 ** Schmidt A et al. Catheter Cardiovasc Interv. 2010 Dec 1;76(7):1047-54
FMRP 2016 |
DCB-BTK Evidence: The LEIPZIG Registry
Single Center Registry • 132 Patients (CLI 100%) • Diabetes 100% • Mean lesion length 13 cm • CTO’s 80%
IN.PACT Amphirion vs. PTA in CLI DM patients
Liistro F et al. Ciculation. 2013 Aug 6;128(6):615-21
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DCB-BTK Evidence: small RCT DCB-DES
Single Center RCT • 50 Patients (CLI + CI) • Mean lesion length : 14,8 cm (DCB) vs 12,7 cm (DES) ; p=0,33) IN.PACT Amphirion vs. DES : 6 m results
•Binary restenosis: 58% vs. 28% (p=0.045) •LLL: 1.35±0.2 vs. 1.15±0.3 (p=0.62) •TLR: 14.3% vs. 7.4 (p=0.21)
>50% Restenosis Length (cm) Group DES: 3.6 ± 1.5 Group PCB: 4.3 ± 1.6
p=0.16
P.M. Kitrou, MD, PhD – LINC 2014
Late Lumen Loss (mm) Group DES: 1.35 ± 0.2 Group PCB: 1.15 ± 0.3
P=0.62
FMRP 2016 |
DCB-BTK Evidence : BIOLUX P-II
• prospective, multi-center 1:1 RCT: DEB vs. POBA
• primary endpoints:
– clinical: 30-day Major Adverse Events (MAE)
– efficacy: 6-month target lesion primary patency
72 subjects enrolled (Rutherford 2-5)
DEB (N=36) Passeo-18 Lux
POBA (N=36) Passeo-18
30-day FU (N=35)
30-day FU (N=35)
6-month FU (N=33)
6-month FU (N=30)
12-month FU
24 M. Brodmann, MD – LINC 2014
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• IN.PACT DEEP : prospective, multi-center 2:1 RCT: DEB vs. POBA
358 subjects enrolled (Rutherford 4-6)
DEB (N=239) POBA (N=119) In.Pact Amphirion standard PTA
Angio eligible = 168 DEB = 113 PTA = 54
Angio excluded = 191 DEB = 126 PTA = 65
Angiographic outcomes Clinical outcomes
25 Zeller et al. JACC 2014, 64 ; 15
DCB vs. PTA in C IN.PACT DEEP
FMRP 2016 |
DCB-BTK Evidence overall…
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• DEVICE RELATED?
• STUDY DESIGN RELATED?
• BTK/CLI RELATED?
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DEVICE RELATED?
DCB PTA p
12-month LLL (mm) 0.61±0.78 0.62±0.78 0.950
“Old” IN.PACT Amphirion “New” (Next Gen) IN.PACT Pacific Admiral
Coating method
Manually-coated on folded balloon
Automatically-coated on semi-inflated balloon
Lack of drug effect?
Animal studies confirmed balloon material can impact drug delivery: - New design delivered more drug to vessel Folds protect the drug - New design had less residual drug on balloon Better drug release
With the courtesy of T. Zeller, presented @ LINC 2015
FMRP 2016 |
• No standardized wound care protocols?
• No standardized major amputation protocols?
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STUDY DESIGN RELATED?
Zeller T, JACC 2014;64:1568-76 – Liistro F, Circulation 2013;128(6):615-21
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• Is there an essential fysiological difference between SFA and BTK? (IN.PACT SFA vs IN.PACT DEEP)
• Is there an essential difference between CLI and CI patients in PTX response/risk?
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BTK/CLI RELATED?
FMRP 2016 |
Lutonix BTK
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Lutonix BTK
32 Steiner S., presented @LINC 2016, Leipzig,Germany
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New horizons….
• Direct drug delivery in the vessel wall
Bullfrog® micro-infusion device (Mercator Medsystems)
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CONCLUSION • DES are effective for short BTK lesions in terms of primary
patency, fTLR & amputation free survival but randomized trials miss superiority in hard clinical outcome of RB-classification shift & woundhealing.
• There is no proven clinical advantage across all studies between ANY DCB & control groups.
• The lack of wound treatment-/amputation protocols are partially responsable for these issues
• Further research with new technologies is mandatory in the challenging DCB-BTK field
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FMRP 2016 | 35
LINC AP 2016, Hong Kong
Drug delivery devices for BTK treatment
Koen Deloose , MD
Marc Bosiers Koen Deloose Joren Callaert
A.Z. Sint-Blasius, Dendermonde
Patrick Peeters Jürgen Verbist
W. Van den Eynde
OLV Hospital, Aalst
Lieven Maene Roel Beelen
R.Z. Heilig Hart, Tienen
Koen Keirse Bart Joos
Imelda Hospital, Bonheiden