Transcript Folie 1 - CRTOnline

Definitive Therapies – How to Optimize
DCB Outcomes: Lessons from the
European Trials
Prof. Thomas Zeller
Department Angiology
University Heart-Center Freiburg - Bad Krozingen
Bad Krozingen , Germany
Faculty Disclosure
Thomas Zeller, MD
For the 12 months preceding this presentation, I disclose the
following types of financial relationships:
• Honoraria received from: Abbott Vascular, Angioslide, Bard Peripheral
Vascular, Veryan, Biotronik, Boston Scientific Corp., Cook Medical, Cordis
Corp., Gore & Associates, Medtronic, Spectranetics, Straub Medical,
TriReme, VIVA Physicians
• Consulted for: Abbott Vascular, Bard Peripheral Vascular, Boston Scientific
Corp., Cook Medical, Gore & Associates, Medtronic, Spectranetics
• Research, clinical trial, or drug study funds received from:
480 biomedical, Bard Peripheral Vascular, Veryan, Biotronik, Cook Medical,
Cordis Corp., Gore & Associates, Abbott Vascular, Medtronic,
Spectranetics, Terumo, TriReme, Volcano
Drug-Coated Balloons
• Benefits
•
•
•
•
More uniform drug delivery than drug-eluting stents
Native vessel maintained
Reduced requirement for DAPT (if stents are avoided)
Re-interventions are less challenging than in-stent-restenosis
• Limitations
• Procedural effectiveness, same as POBA
• Recoil
• Calcium
• Dissections
• Lesion length
• Increasing bail-out stent rate with increasing lesion length
• Increases cost
• May negatively affect procedural outcomes
3 |
Calcium May Present a Challenge
• Only 20% of Paclitaxel transfers into the vessel wall1
• Calcification can increase the loss of anti-proliferative
drug and impair uptake2
• Medial calcification is common in patients with
diabetes and chronic kidney disease3
2.
1.
Kelsch et al. Invest Radiol 2011
Schnorr Expert Rev Med Device 10(1), 105-114 (2013)
3.
Jude et al. Diabetic Medicine 27,4-14 (2010)
Impact of Calcium
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•
•
•
•
Barrier to optimal dilatation
Barrier to optimal drug absorption
Underestimated by angiography
Key cause of severe dissections
Bilateral / circumferential calcium ranked as most
severe by different calcium grading systems
• Highly prevalent in:
– Elderlies
– Diabetics
– Kidney disease
1. Fanelli F et al. Calcium burden assessment and impact on drug-eluting balloons in peripheral arterial disease. Cardiovasc Intervent Radiol. 2014
Aug;37(4):898-907
2. Rocha-Singh KJ, Zeller T, Jaff MR. Peripheral arterial calcification: prevalence, mechanism, detection, and clinical implications. Catheter Cardiovasc
Interv. 2014 May 1;83(6):E212-20
3. Fitzgerald PJ et al. Contribution of localized calcium deposits to dissection after angioplasty. Circulation. 1992; 86(1):64-70
4. Shanahan M et al. Medial Localization of Mineralization-Regulating Proteins in Association With Mönckeberg's Sclerosis : Evidence for Smooth Muscle
Cell -Mediated Vascular Calcification. Circulation. 1999;100:2168-2176
5. Moe SM, Chen NX. Mechanisms of vascular calcification in chronic kidney disease. J Am Soc Nephrol. 2008 Feb;19(2):213-6
6. Bertoni AG, Kramer H, Watson K, Post WS. Diabetes and Clinical and Subclinical CVD. Glob Heart. 2016 Sep;11(3):337-342
DCB and Calcium
(Fanelli et al. Cardiovasc Intervent Radiol. 2014)
Calcium: potential barrier to optimal drug absorption
Circumferential distribution strongest influencing factor
N=60
•
•
•
SFA lesions  6 cm (de-novo)
CTO: 31.7%
DCB with standard pre-dilatation
• a = <3 cm; b = >3cm
• Calcium evaluation by CTA (circumf.) and
DSA (longitud.)
1. Fanelli F, Cannavale A, Gazzetti M, Lucatelli P, Wlderk A, Cirelli C, d'Adamo A, Salvatori FM. Calcium burden assessment and impact on drug-eluting
balloons in peripheral arterial disease. Cardiovasc Intervent Radiol. 2014 Aug;37(4):898-907
Courtesy M. Landini
DCB and Calcium
(Tepe et al. J Endovasc Ther. 20151 )
Not length, nor location but bilateral Calcium
distribution observed as strongest predictor of outcome
N=91 (retrospective)
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•
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SFA lesions  5.7 cm
Restenotic: 45.1%
CTO: 33.0%
6-month LLL (primary
endpoint) by Angio Core lab
adjudication
1. Tepe G, Beschorner U, Ruether C, Fischer I, Pfaffinger P, Noory E, Zeller T. Drug-Eluting Balloon Therapy for Femoropopliteal Occlusive
Disease: Predictors of Outcome With a Special Emphasis on Calcium. J Endovasc Ther. 2015 Oct;22(5):727-33
2. Rocha-Singh KJ, Zeller T, Jaff MR. Peripheral arterial calcification: Prevalence, mechanism, detection and clinical implications. Catheter
Cardiovasc Interv. 2014;83:E212-220.
SFA-Stent Deployment Evaluation
Stent Compression - Leipzig Data
Angio AP projection
% MLD 15%
Angio LAO projection
% MLD 42%
Impaired Primary Patency
due to Residual Stenosis following BMS
p< 0.05
Bausback Y et al. JEVT2014
DCB and Stenting
(Tepe et al. J Endovasc Ther. 2015 )
Stents may not necessarily improve DCB results
N=91 (retrospective)
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•
•
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SFA lesions  5.7 cm
Restenotic: 45.1%
CTO: 33.0%
6-month LLL (primary
endpoint) by Angio Core lab
adjudication
1. Tepe G, Beschorner U, Ruether C, Fischer I, Pfaffinger P, Noory E, Zeller T. Drug-Eluting Balloon Therapy for Femoropopliteal
Occlusive Disease: Predictors of Outcome With a Special Emphasis on Calcium. J Endovasc Ther. 2015 Oct;22(5):727-33
SFA 12-Month Primary Patency
PTA, BMS, DES and DEF LE Sub-analyses by Lesion Length
100
RESILIENT3
90
Zilver2
SUPERB8
SIROCCO6
BMS
DURABILITY II9
80
COMPLETE5
70
PTA
FAST1
60
DES
VIBRANT7
(BMS arm)
50
RESILIENT3
40
THUNDER4
DEFINITIVE LE
Subgroup Analysis by
Lesion Length
Linear (BMS)
Zilver 2
30
20
10
0
2
4
6
8
10
12
14
16
18
20
1. Krankenberg et al. Circulation. 2007;
5. Laird, ISET 2012
2. Dake et al. Circ Cardiovasc Interv. 2011
6. Duda et al. J Endovasc Ther 2006
3. Laird et al. Circ Cardiovasc Interv. 2010
7. Ansel, VIVA 2010
4. Tepe et al. NEJM 2008;358:689-99
8. Rosenfield VIVA 2012
9. Matsumura ISET 2012
IN.PACT GLOBAL LONG LESIONS IMAGING COHORT (≥15 CM)
Primary Patency in non-stented subgroup
13
Primary Patency by Lesion Length
PCR Perrpheral Istanbul2015 | IN.PACT Global Complex Lesions| November 28, 2015
DAART = Directional Atherectomy +
Anti-Restenotic Therapy
• Mechanically re-canalize the vessel without
overstretch
• Remove the perfusion barrier
• Reduce the likelihood of bail-out stenting
and preserve the native vessel
14 |
DEFINITIVE Ca++ demonstrated calcified disease can be treated
with DA and embolic protection
Min lumen diameter (mm)
• Bail-out stent rate: 4.1%
Baseline
1
• Flow-limiting dissection rate: 1.5%
• Achieved maximal lumen gain
2
1.1
1
Post-DA
Post-adjunctive therapy
3.2
3.7
15 |
1. Roberts Cath Cardiovasc Interven 84:236-244(2014) 2. Data on file
Published DAART Data
• Procedure Results
– < 30% residual stenosis achieved in all
cases
– No procedure-related AEs
– Bail-out stenting rate: 6.5% (2)
• 1 Year Results
– Primary Patency (via duplex) = 90% (27/30)
– Freedom from MAE 87% (26/80)
Authors’ Conclusion: DA and DCB may represent a potential alternative
strategy for the treatment of femoro-popliteal severely calcified lesions.
These very promising data and the considered hypothesis have to be
confirmed in a multicenter randomized trial.
Cioppa et al. CV Revasc. Med. 2012 Jul-Aug:219-23.
DEFINITIVE AR
1-Year Outcomes
DEF AR – The Value of Luminal Gain
DEFINITIVE AR Case Example: DAART Arm
Sub-optimal Debulking
Baseline
59% residual stenosis
Post atherectomy
DEFINITIVE AR Case Example: DAART Arm - Suboptimal Debulking
34% residual stenosis
Post DAART
DCB Inflations
DEFINITIVE AR Case Example: DAART Arm - Suboptimal Debulking
Clinically-driven TLR 349 days post
DAART procedure
Occlusion begins at site of
sub-optimal debulking
Periprocedural Complications
(Per CEC)
DAART
(N= 48)
DCB
(N = 54)
p-value
6% (3/48)
0/54
0.101
No Intervention
1
0
Surgical Intervention
0
0
Endovascular Intervention
2
0
Dissection (flow-limiting, Grade C/D)
2% (1/48)
19% (10/54)
No Intervention
1
6
Surgical Intervention
0
0
Endovascular Intervention
0
4
4% (2/48)
0/54
No Intervention
0
0
Surgical Intervention
0
0
Endovascular Intervention
2
0
Distal Embolization
Perforation
0.009
0.219
Co-Principal Investigators
Krishna Rocha-Singh, MD
Chief Scientific Officer
Prairie Heart Institute of Illinois
Brian DeRubertis MD, FACS
Associate Professor of Surgery
UCLA Division of Vascular Surgery
• The REALITY Study evaluates patient outcomes with adjuctive use of Medtronic
HawkOne™ or Medtronic TurboHawk ™ and Medtronic IN.PACT™ Admiral™
drug-coated balloon.
• The multi-center, international, prospective, single-arm study will enroll up to
250 subject at up to 15 sites.
• The study includes angiographic and duplex ultrasound core lab adjudication.
Primary patency is assessed by duplex ultrasound at 12-months.
• Patients are followed up to 24 months to determine clinically driven target
lesion revascularization (CD-TLR).
• The study is sponsored and managed by VIVA physicians with support from
Medtronic through an external research project grant.
| For Medtronic presentation use only, do
not copy or distribute
25
Co-Principal Investigators
Krishna Rocha-Singh, MD
Chief Scientific Officer
Prairie Heart Institute of Illinois
Brian DeRubertis MD, FACS
Associate Professor of Surgery
UCLA Division of Vascular Surgery
 Consent 250 subjects
 Goal Enrollment 150 subjects
 Ten U.S. Sites
 Lesion length 8-18cm
 Occlusion length 6-10cm
 3 German Sites
 Lesion length up to 25cm
| For Medtronic presentation use only, do
not copy or distribute
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Optimizing DCB Intervention
Proposed Fem-Pop Treatment Algorithm
Each femoropopliteal lesion
Pre-Dilatation with
1:1 sized balloon
Flow-limit Dissection or
residual stenosis >50%?
Flow-limit Dissection or
residual stenosis >50%?
NO
YES
NO
Directional
Atherectomy
DEB
YES
Stent
Treatment Options to Overcome DCB Limitations
Summary
• DCB offer promising results in the treatment of femoro-popliteal
lesions
• However, limitations exist in complex lesion morphologies such as:
• Severely calcified lesions
• Acute residual stenosis > 30%
• Lesion length
• DEFINITIVE AR resulted by trend in better outcomes in those
challenging lesion subsets for the combination of DA & DEB
• “spot” atherectomy might be a cost effective strategy
• A sufficiently powered study to confirm this potential benefit is
mandatory
• Lithoplasty offers potential advantages when combined with DCB
or used as a DCB