Current meta-analysis comparison between DCB and
POBA in below-the-knee therapy
Jihad A. Mustapha, MD, FACC, FSCAIDirector of Cardiovascular Research
Metro Health Hospital
Wyoming, MI
Associate Clinical Professor of Medicine
Michigan State University College of Osteopathic Medicine
E. Lansing, MI
Disclosure Statement of Financial Interest
• Consulting Fees/Honoraria • Abbott Vascular• Bard Peripheral Vascular• Boston Scientific• Cardiovascular Systems, Inc.• Cook Medical• Medtronic• Spectranetics• Terumo
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
Infrapopliteal or “Below the knee” Arterial Disease
• Risk factors include diabetes, chronic kidney disease, and advanced age ( all on the rise )
• Progresses to critical limb ischemia (CLI)
• Disease may be multi-level
• Higher risk for amputation with shorter amputation-free survival
• Goal: Re-establish direct flow through at least one infrapopliteal artery to reduce pain and promote wound healing.
Gray BH, Diaz-Sandoval LJ, Dieter RS, Jaff MR, White CJ, Peripheral Vascular Disease Committee for the Society for
Cardiovascular A and Interventions. SCAI expert consensus statement for infrapopliteal arterial intervention appropriate use.
Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.
2014;84:539-45.
Notice, no mention
of preventing Amp
Types Vascular Smooth Muscle cells (VSMC)
• The two ends of a spectrum of VSMC: 1.Proliferative, synthetic VSMCs
• 2.Quiescent, contractile VSMCs
• 3.Intermediate phenotypes exist • Differentiation and proliferation of VSMCs are not mutually exclusive
Depending on the signals present in their local environment, contractile VSMCs can acquire distinct phenotypes with the ability to:
• migrate
• proliferate promote ECM production
• elicit inflammatory signals
• and/or calcification
Types Vascular Smooth Muscle cells (VSMC)
• The phenotypic modulation of VSMCs is determined by the environmental signals: – mechanical forces
– endocytosis of specific molecules
– growth factors that influence expression of a panel of VSMC-specific genes
– inflammatory cytokines
– calcium-phosphate homeostasis
– oxidized phospholipids, retinoic acid
– involves multiple signaling pathways including MAPK kinases, Rho, Notch, BMP
– and β-catenin signaling
Location and Features Associated Condition(s)
Calcific atherosclerosis Intimal; ossification Atherosclerosis, hyperlipidemia; osteoporosis; hypertension; inflammation
Calcific medial vasculopathy(Monckeberg’s medial calcific sclerosis)
Tunica media Type 2 diabetes mellitus; end-stage renal disease; hyperphosphatemia; amputation
Elastocalcinosis Internal elastic lamina/internaExternal elastic Externa
Pseudoxanthoma elasticum; Marfan syndrome ( concentric tibial calcification )
Calcific uremic arteriolopathy Microvessels; amorphous End-stage renal disease;
Infrapopliteal Treatment Trials –Disappointing Results for 20 Years
• Distal Bypass
• POBA
• BMS
• DES (for mid and distal tibials)
• DCB
• Other
Bosiers, M., Deloose, K., Moreialvar, R., Verbist, J., & Peeters, P. (2008). Current status of infrapopliteal artery stenting in patients with critical limb ischemia. Jornal Vascular Brasileiro, 7(3), 248-
255.
Rocha‐Singh, K. J., Jaff, M., Joye, J., Laird, J., Ansel, G., & Schneider, P. (2012). Major adverse limb events and wound healing following infrapopliteal artery stent implantation in patients with
critical limb ischemia: The XCELL trial. Catheterization and Cardiovascular Interventions, 80(6), 1042-1051.
Meta-analysis of infrapopliteal angioplasty for chronic critical limb ischemia.
Journal of Vascular Surgery, Volume 47, Issue 5, 2008, 975–981.e1
Bypass Graft
• Option for good surgical candidates
• Comorbidities, inadequate conduit, lack of good distal target limit eligibility for many CLI patients
• Index limb re-operation within 3 months, hospital re-admission, and > 3 month wound healing time have been reported in the 50% range
• High morbidity/mortality rates & costBosiers, M., Deloose, K., Moreialvar, R., Verbist, J., & Peeters, P. (2008). Current status of infrapopliteal artery stenting in patients with critical limb ischemia. Jornal Vascular Brasileiro, 7(3), 248-
255.
Rocha‐Singh, K. J., Jaff, M., Joye, J., Laird, J., Ansel, G., & Schneider, P. (2012). Major adverse limb events and wound healing following infrapopliteal artery stent implantation in patients with
critical limb ischemia: The XCELL trial. Catheterization and Cardiovascular Interventions, 80(6), 1042-1051.
POBA
Meta-analysis estimates of primary patency (black line), secondary patency (gray line), limb salvage (red line).
Marcello Romiti, Maximiano Albers, Francisco Cardoso Brochado-Neto, Anai Espinelli S. Durazzo, Carlos Alberto Bragança Pereira, Nelson De Luccia. Meta-analysis of infrapopliteal angioplasty for chronic critical limb ischemia. Journal of Vascular Surgery, Volume 47, Issue 5, 2008, 975–981.e1
Meta-analysis (1990-2006):
• Limb salvage rate was high
• Primary and secondary
patency were low
• PTA had inferior primary and
secondary patency but
comparable limb salvage to
open surgical procedures
POBA
Kaplan-Meier life-table analysis of outcomes after angioplasty for CLI. Dashed line –
portion of plot where the SE is greater than 10%.
• Limb salvage rate was high
• Primary and secondary
patency were low
• Purpose of treatment in
this population is symptom
relief rather than long-term
patency
• Risk factor analysis
showed hypertension,
multiple segment lesions,
more distal lesions, and
TASC D lesions were
predictors of worse long-
term outcomes
Toshifumi Kudo, Fiona Chandra, and Samuel Ahn. The effectiveness of percutaneous transluminal angioplasty
for the treatment of critical limb ischemia: A 10-year experience. Journal of Vascular Surgery, Volume 41, Issue
3, 2005, 423-435
BMS
• Good limb salvage rates
• 12-month freedom from TLR 54.3%
• Rate of AEs 63.3%, largely due to high rate of TLR
Rocha-Singh, K. J., Jaff, M., Joye, J., Laird, J., Ansel, G., Schneider, P. and The VIVA Physicians (2012), Major adverse
limb events and wound healing following infrapopliteal artery stent implantation in patients with critical limb ischemia:
The XCELL trial. Cathet. Cardiovasc. Intervent., 80: 1042–1051. doi:10.1002/ccd.24485
12-Month amputation-free survival and limb salvage curves.
DES
• SES group superior to PTA with freedom from death, TLR, bypass, amputation, and RC ≥4.
• 12 month vessel patency higher in SES vs. PTA (75% vs. 57.1%)
Fusaro, M., Cassese, S., Ndrepepa, G., Tepe, G., King, L., Ott, I., ... & Kastrati, A. (2013). Drug-eluting stents for revascularization of infrapopliteal arteries: updated meta-analysis of randomized
trials. JACC: Cardiovascular Interventions, 6(12), 1284-1293.
Scheinert, D., Katsanos, K., Zeller, T., Koppensteiner, R., Commeau, P., Bosiers, M., ... & Van Ransbeeck, M. (2012). A prospective randomized multicenter comparison of balloon angioplasty
and infrapopliteal stenting with the sirolimus-eluting stent in patients with ischemic peripheral arterial disease: 1-year results from the ACHILLES trial. Journal of the American College of
Cardiology, 60(22), 2290-2295.
META-ANALYSIS
• DES reduces risk of TLR, restenosis and amputation compared to PTA or BMS
• DES had no significant difference on mortality or RC improvement at 1 year
ACHILLES TRIAL
DES
• DES trials limited to primarily focal lesions
• Stent deformation limits use in distal vessels
A: Overall distribution and rates of stent fractures and compressions in various infrapoplitealanatomical levels
B: Anatomical relationship of distal anterior tibialartery may render the vessel more prone to stent fatigue
Scheinert, D. (2007). Update: drug-eluting stents in tibial arteries. Endovasc. Today, 8, 71-74.
Karnabatidis, D., Katsanos, K., Spiliopoulos, S., Diamantopoulos, A., Kagadis, G. C., & Siablis, D. (2009). Incidence, anatomical location, and clinical
significance of compressions and fractures in infrapopliteal balloon-expandable metal stents. Journal of Endovascular Therapy, 16(1), 15-22.
DCBMultiple randomized trials comparing DCB to POBA with varied results:
DEBATE-BTK: DCB associated with significant reduction in binary restenosis, TLR and vessel occlusion at 12 months
DEBELLUM: DCB demonstrated reduction in restenosis at 6 months
IN.PACT DEEP: DCB had comparable efficacy, increased major amputation rates.
BIOLUX: DCB outcomes comparable to PTA
Fanelli, F., Cannavale, A., Boatta, E., Corona, M., Lucatelli, P., Wlderk, A., ... & Salvatori, F. M. (2012). Lower limb multilevel treatment with drug-eluting balloons: 6-month results from the
DEBELLUM randomized trial. Journal of Endovascular Therapy, 19(5), 571-580.
Zeller, T., Beschorner, U., Pilger, E., Bosiers, M., Deloose, K., Peeters, P., ... & Brodmann, M. (2015). Paclitaxel-Coated Balloon in Infrapopliteal Arteries: 12-Month Results From the BIOLUX P-
II Randomized Trial (BIOTRONIK'S-First in Man study of the Passeo-18 LUX drug releasing PTA Balloon Catheter vs. the uncoated Passeo-18 PTA balloon catheter in subjects requiring
revascularization of infrapopliteal arteries). JACC: Cardiovascular Interventions, 8(12), 1614-1622.
DCBDEBATE BTK
- Binary restenosis 27% (DCB) vs. 74.3% (PTA)
- Freedom from TLR significantly higher with DCB
- No major amputations in DCB group
IN.PACT DEEP- Binary restenosis 41% (DCB) vs. 35.5% (PTA)
- Clinically driven TLR comparable, 11.9% (DCB) vs. 13.5% (PTA)
- 12 month major amputation 8.8% (DCB) vs. 3.6% (PTA)
Liistro, F., Porto, I., Angioli, P., Grotti, S., Ricci, L., Ducci, K., ... & Bolognese, L. (2013). Drug-eluting balloon in peripheral intervention for below the knee angioplasty evaluation (DEBATE-BTK):
a randomized trial in diabetic patients with critical limb ischemia. Circulation, CIRCULATIONAHA-113.
Zeller, T., Baumgartner, I., Scheinert, D., Brodmann, M., Bosiers, M., Micari, A., ... & Kent, K. C. (2014). Drug-eluting balloon versus standard balloon angioplasty for infrapopliteal arterial
revascularization in critical limb ischemia: 12-month results from the IN. PACT DEEP randomized trial. Journal of the American College of Cardiology, 64(15), 1568-1576.
SIZE MATTERS !!!
RVD = 2.89 mm
RVD = 2.44 mm
DEBATE BTK IN.PACT DEEP
Potential Reasons for Success:
• Average DEBATE DCB balloon size was 0.56 larger than IN.PACT
• DEBATE pre-dilatation size ratio closer to 1:1 versus 0.9:1 with IN.PACT
• DEBATE acute luminal gain higher
Other Treatments
• Cryoplasty – No long term benefit
• Cutting balloon – No long term benefit
• Scoring balloon – No long term benefit
Based on comparative analysis
Is POBA the best option?• Optimal infrapopliteal treatment modality remains controversial and PTA
remains standard of care
• Contemporary meta-analysis performed (2005-2015) to assess current PTA outcomes
• 1-year outcomes from contemporary meta-analysis comparable to Romitimeta-analysis:
Technical success: 91% vs. 89%
Primary patency: 63% vs. 58%
Major amputation: 15% vs. 14%
All-cause mortality: 15% vs. 13%
• Infrapopliteal PTA outcomes have not changed over last decade despite advanced knowledge and techniques
Mustapha, J. A., Finton, S. M., Diaz-Sandoval, L. J., Saab, F. A., & Miller, L. E. (2016). Percutaneous Transluminal
Angioplasty in Patients With Infrapopliteal Arterial Disease Systematic Review and Meta-Analysis. Circulation:
Cardiovascular Interventions, 9(5), e003468.
Calcific medial vasculopathy(Monckeberg’s medial calcific sclerosis)
Tunica media Type 2 diabetes mellitus; end- stage renal disease; hyperphosphatemia; amputation
Elastocalcinosis Internal elastic lamina/internaExternal elastic externa
Pseudoxanthomaelasticum; Marfansyndrome (concentric tibial calcification)
The real problem is NOT what we think is the problem
• It is ALL in the WALL
Thank you
Jihad A. Mustapha, MD, FACC,
FSCAIDirector of Cardiovascular Research
Metro Health Hospital
Wyoming, MI
Associate Clinical Professor of Medicine
Michigan State University College of Osteopathic Medicine
E. Lansing, MI
Current meta-analysis comparison between DCB and
POBA in below-the-knee therapy
Jihad A. Mustapha, MD, FACC, FSCAIDirector of Cardiovascular Research
Metro Health Hospital
Wyoming, MI
Associate Clinical Professor of Medicine
Michigan State University College of Osteopathic Medicine
E. Lansing, MI
