Current meta - PDF document

1 Current meta - analysis comparison betw
Current meta - analysis comparison between DCB and POBA in below - the - knee therapy Jihad A. Mustapha, MD, FACC, FSCAI Director 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/ar

2 rangement or affiliation with the organi
rangement 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 i nfrapopliteal artery to reduce pain and promote wound healing. Gray BH, Diaz - Sandoval LJ, Dieter RS, Jaff MR, White CJ, Peripheral Vascular Disease Co

3 mmittee for the Society for Cardiovascu
mmittee 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 o f 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 sign

4 als present in their local environment,
als 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 multipl

5 e signaling pathways including MAPK kina
e 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 ( M nckeberg’s medial calcific sclerosis) Tunica media Type 2 diabetes mellitus; end - stage renal disease; hyperphosphatemia ; amputation Elastocalcinosis Internal elastic lamina/ interna External elastic Externa Pseudoxanthoma elasticum ; Marfan syndrome ( concentric tibial calcification ) Calcific uremic arteriol

6 opathy Microvessels ; amorphous End - s
opathy 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 sten

7 t implantation in patients with critica
t 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 • O ption 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 morbidit

8 y/mortality rates & cost Bosiers , M.,
y/mortality rates & cost 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. POBA Meta - analysis estimates of primary patency (black

9 line), secondary patency (gray line),
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

10 life - table analysis of outcomes a
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

11 - year experience. Journal of Vascular S
- 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

12 • SES group superior to PTA with free
• 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 bal

13 loon angioplasty and infrapopliteal st
loon 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 Ame rican 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

14 infrapopliteal anatomical levels B: Ana
infrapopliteal anatomical levels B: Anatomical relationship of distal anterior tibial artery 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. DCB Multiple randomized trials comparing DCB to POBA with varied res

15 ults:  DEBATE - BTK: DCB associated w
ults:  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., B

16 eschorner , U., Pilger , E., Bosiers ,
eschorner , 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 Pa sseo - 18 PTA balloon catheter in subjects requiring revascularization of infrapopliteal arteries). JACC: Cardiovascular Interventions, 8(12), 1614 - 1622. DCB DEBATE BTK - Binary restenosis 27% (DCB) vs. 74.3% (PTA) - Freedom from TLR significantly higher with DCB - No major amputations in D

17 CB group IN.PACT DEEP - Binary restenos
CB 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 (DEB ATE - 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). Dru

18 g - eluting balloon versus standard ball
g - 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 C ollege 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

19 long term benefit • Scoring balloon â
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 Romiti meta - analysis:  Technical success: 91% vs. 89%  Primary patency: 63% vs. 58%  M ajor amputation: 15% vs. 14%  All - cause mortality: 15% vs. 13% • Infrapopliteal PTA outcomes have not changed over last decade despite adv

20 anced knowledge and techniques Mustapha,
anced 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 ( M nckeberg’s medial calcific sclerosis) Tunica media Type 2 diabetes mellitus; end - stage renal disease; hyperphosphatemia ; amputation Elastocalcinosis Internal elastic lamina/ interna External elastic externa Pseudoxanthoma elasticum ; Marfan syndrome (concentric tib

21 ial calcification ) The real problem is
ial 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, FSCAI Director 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, FSCAI Director of Cardiovascular Research Metro Health Hospital Wyoming, MI Associate Clinical Professor of Medicine Michigan State University College of Osteopathic Medicine E. L