Tratamiento endovascular eje fémoro-poplíteo: actualización de estudios y “new data”

Dr Costantini Ricardo – Cardioangiología Intervencionista

Jornadas Intervencionistas

Arteriales y Venosas del Hospital Austral

(JAVA) 2019

5 Yr Mortality – Enfermedad Vascular Periférica

Para aquellos que han sufrido amputación

Varu VN; Hogg ME; Kibbe MR. Critical limb ischemia J Vasc Surg 2010; 51: 230 - 241

Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg. 2000;31(1 pt 2):S1–S296

Weighted mean prevalence of intermittent claudication in large population-based studies.

Prevalencia de enfermedad vascular periférica:4% > 40 años

15% - 20% > 65 añosCirculation 2006; 113: 463 - TASC II – J Vasc Surg 2007

N Engl J Med 2001 Vol 344, 21: 1608

Circulation. 2007;116:2203-2215

Consensus Definitions From Peripheral Academic Research Consortium (PARC) J Am Coll Cardiol 2015;65:931–41)

Mortalidad en Enfermedad Vascular Periférica

Disminución del riesgo de infarto, stroke y muerte CV

Mejoría de los síntomas, calidad de vida y prevención de amputación

Discontinuación habito tabáquico Discontinuación habito tabáquico

Programa de caminata / ejercicios Programa de caminata / ejercicios

Control de presión arterial Cilostazol

Estatinas: dosis altas Cuidado adecuado de pies: cremas, tratamiento y prevención de micosis, prevención de puntos de presión anormal con ortesis, cuidados de uñas.

Tratamiento antiplaquetario Revascularización

Farzin Fakhry; Sandra Spronk et alJAMA. 2015;314(18):1936-1944

(ERASE Trial)Endovascular Revascularization And Supervised Exercise

212 patients: supervised exercise (n = 106) vs PTA plus supervised exercise (n = 106)

The primary outcome was maximum walking distance at12 months assessed during a

graded treadmill test (maximum duration,

30 minutes).

Farzin Fakhry; Sandra Spronk et alJAMA. 2015;314(18):1936-1944

(ERASE Trial)Endovascular Revascularization And Supervised Exercise

212 patients: supervised exercise (n = 106) vs PTA plus supervised exercise (n = 106)

Piotr Sobieszczyk and Andrew Eisenhauer - Circulation. 2013;128:749-757

POBA

DrugsElutingsStents

AtherectomyStents

Drugs-Coated

Balloons

(BASIL trial): Bypass versus PTA in severe ischaemia of the leg

Lancet 2005; 366: 1925–34

Since 1999 - finished 2004452 patients underwent randomisation at one of 27 UK hospitals

Primary endpoint (amputation-free survival) at 1 year was 68% and at 3 years was 57% for those assigned to surgery first;

Survival at 1 year was 71% and at 3 years was 52% for those randomised to angioplasty first.

(ABSOLUTE trial)The randomized Balloon Angioplasty Versus Stenting With Nitinol Stents in the

Superficial Femoral Artery

104 pts with severe intermittent claudication (Rutherford class 3) or chronic critical limb ischemia with either rest pain(Rutherford class 4) or ischemic ulcers (Rutherford class 5) and a 50% stenosis or occlusion of the ipsilateral SFA with a target lesion length 30 mm and at least 1 patent (50% stenosis) tibioperoneal runoff vessel.

EP 1°= Restenosis rates at 2 years were 45.7% versus 69.2% in favor of primary

stenting compared with balloon angioplasty with optional stenting (p=0.03).

N Engl J Med 2006; 354:1879-1888

N Engl J Med 2006; 354:1879-1888

The randomized Balloon Angioplasty Versus Stenting With Nitinol Stents in the

Superficial Femoral Artery (ABSOLUTE) trial

Prevalence and Clinical Impact ofStent Fractures After Femoropopliteal Stenting

Dierk Scheinert, Susanne Scheinert, Matthias Ulrich, Giancarlo Biamino, Andrej SchmidtJ Am Coll Cardiol 2005;45:312–5

SMART stents (Cordis, ) were used in 52, SelfX stents (Abbott Medical Devices) in24, and Luminex stents (BARD) in 45 limbs, respectively.

Non fracturedstent

Fracturedstent

Fracture rates

13.2% = length 8 cm,

42.4% = 8 to 16 cm,

52.0% = > 16 cm

Stent fractures were detected in 37.2%

Michael Werk; Thomas Albrecht et al of PACIFIER Trial - Circ Cardiovasc Interv. 2012;5:00-00

(PACIFIER Trial) Paclitaxel-Coated Balloons Reduce Restenosis After Femoro- Popliteal Angioplasty

82.2

2.4

52.4

20.6

0

10

20

30

40

50

60

70

80

90

Permeabildad 1° TLR clínica

DCB PTA

p<0.001

p<0.001

Gunnar Tepe; John Laird et al - Circulation. 2015;131:495-502

(IN.PACT SFA) Treatment Effect Using a Drug-Coated Balloon for Femoropopliteal

Lesions: 12-Month Results

%

✓ No major target limb amputations in either group (p>0.999) and low thrombosis rates of 1.5% in the IN.PACT™ Admiral™ DCB group, compared to 3.8% in the PTA group (p=0.243).

✓ In women, the primary patency rate was 73.3% for the IN.PACT™ Admiral™

DCB, compared to 45.8% in the PTA group (p<0.001).

✓In diabetic patients, the primary patency rate was 76.7% in the IN.PACT™

Admiral™ DCB group, compared to 42.3% in the PTA group (p<0.001).

Durability of Treatment Effect Using a Drug-Coated Balloon for Femoropopliteal Lesions:24-Month Results of IN.PACT SFA

DCB vs PBA for femoropopliteal artery diseaseMetaanalysis of randomized clinical trial

Trial Tipo DCB Droga Dosis droga

Excipiente

PACIFIER IN.PACT pacific Paclitaxel 3 µ/mm2 Urea

THUNDER Paccocath Paclitaxel 3 µ/mm2 Iopromida

IN.PACT IN.PACT Admiral Paclitaxel 3,5 µ/mm2 Urea

LEVANT 2 Lutonix Paclitaxel 2 µ/mm2 Polysorbato y Sorbitol

Biolux P-I Passeo-18 lux Paclitaxel 3 µ/mm2 Butyryl-tri-n-hexylcitrato (BTHC)

Giacoppo D; Fusaro M; Kastrati A; J Am Coll Cardiol 2016; 9: 1731 – 42)

Trial SFA (%)

SFA +Poplitea

(%)

BTK + SFA + Poplitea

(%)

Longitud lesión (cm)

Oclusión total (%)

Stent bailout(DCB vs PTA -

%)

PACIFIER 100 100 0 6,8 31 9 vs 16

THUNDER 68 34 0 7,4 26 4 vs 22

IN.PACT 93 23 0 8,9 23 16 vs 14

LEVANT 2 91 43 0 6,3 21 2,5 vs 7

Biolux P-I 81 8 4 6 26 2 vs 26

Giacoppo D; Fusaro M; Kastrati A; J Am Coll Cardiol 2016; 9: 1731 – 42

DCB vs PBA for femoropopliteal artery diseaseMetaanalysis of randomized clinical trial

0

10

20

30

40

50

60

70

80

90

100

Permeabilidad primaria Libre de TLR

82

98

8994

6572

In.Pact (n=220) 3,5µ/mm2 ILLUMENATE (n=220) 2 µ/mm2 LEVANT 2 (n= 316) 2 µ/mm2

%

Konstantinos Katsanos ; J Am Coll Cardiol 2016; 9: 1743 – 45

COMPARE-Pilot RCT:1-year results of a randomised comparison of RANGER DCB vs. IN.PACT DCB

in complex SFA lesions (n= 150 400 pts)

Reclutamiento finalizado

Resultados 2020

Jeffrey W. Olin, Christopher J. White et al – JACC 2016; 67: 1338 - 57

Gunnar Tepe, et al IN.PACT Global Study InvestigatorsJ Am Coll Cardiol Intv 2019;12:484–93

Chronic Total Occlusion Cohort in the IN.PACT Global Study

0

20

40

60

80

100

Éxito técnico POBA DCB Stent

91

36

13

54

95

39

27 27

Gpo A (n=43) Fem+BTK Gpo B (n=18) Fem puros

p=0,1*p=1

p= 0,7

p= 0,1

%

Impacto de la presencia de enfermedad infrapoplítea en el tratamiento de obstrucciones femoropoplíteas.

Costantini, R; Telayna JM(h); Telayna, JM; Pataro, M; Acosta Pimentel M.

Mundo real

Longer mean lesion length in DCB studiescorrelates with higher provisional stenting rate

Limitationsof Endovascular Treatment

Provisional Stenting

Treatment of Complex Atherosclerotic Popliteal Artery Disease With a New Self-Expanding Interwoven Nitinol Stent

12-Month Results of the Leipzig SUPERA Popliteal Artery Stent Registry

Scheinert D, Werner M, Scheinert S, Schmidt AJ Am Coll Cardiol Intv 2013;6:65–71

Spot Stenting Versus Long Stenting

After Intentional Subintimal Approach

for Long Chronic Total Occlusions of the Femoropopliteal Artery

Sung-Jin Hong - J Am Coll Cardiol Intv 2015;8:472–80

Real-world performance of paclitaxel drug-eluting bare metal stenting (Zilver PTX) for femoropopliteal occlusive disease

Chronic Total Occlusion 24 (46.1) - Treated lesion length, cm 20.15 ± 12.20

Tran K, Ullery B, Kret M, Lee J - Ann Vasc Surg. 2017;38:90-98

(ZILVERPASS study)Cook Zilver PTX drug-eluting stent versus bypass surgeryfor the treatment of femoropopliteal TASC C&D lesions:

Very complex lesions: 94.55% were occluded

and mean lesion length was

247.11mm

220 patients4 countries13 clinical

centers

The Leipzig Interventional Course - January 2019

MAJESTIC TrialEluvia PES for Femoropopliteal: 3-Year Follow-up

57 patients - long lesions (71± 28 mm); the patency rate: 91% and 82% at 1 and 2 years, respectively.

Kaplan–Meier estimate offreedom from TLR

S Muller Hulsbeck; K Keirse; T Zeller; H Schroe; J Diaz-CartelleCardiovascular and Interventional Radiological Society of Europe (CIRSE) 2017

1-Year All-Comers Analysis of the Eluvia Drug-Eluting Stent for Long Femoropopliteal Lesions After Suboptimal Angioplasty

62 patients were included.

32 patients (52%) presented with life-style-limiting claudication (Rutherford class 3) and 30 patients (48%) with CLTI (Rutherford class 4, n= 14 [23%];

class 5, n = 10 [16%]; class 6, n= 6 [10%]).

The majority of lesions (84%) were de novo. Mean lesion length was 20 ± 12 cm.

The median number of implanted stents was 1.5 stent per limb (interquartile range: 1 to 3).

Theodosios Bisdas et al - JACC Cardiovasc Interv Vol 11(10) 2018

1-Year All-Comers Analysis of the Eluvia Drug-Eluting Stent for Long Femoropopliteal Lesions After Suboptimal Angioplasty

Amputation-free survival was 100% in patients with claudication and 87% in those with critical limb ischemia. Two patients underwent major amputations (at 2 and 6 months).

Aneurysmal degeneration of the arterial wall (mean diameter 14 mm) in 5 patients (8%).

Theodosios Bisdas et al - JACC Cardiovasc Interv Vol 11(10) 2018

A polymer-coated, paclitaxel-eluting stent (Eluvia) versus a polymer-free, paclitaxel-coated stent (Zilver PTX) for

endovascular femoropopliteal intervention (IMPERIAL): a randomised, non-inferiority trial

The superficial femoral and/or proximal popliteal artery lesions up to 140 mm in

length (85mm average).

(Sub-study = longer lesions between 140 and 190 mm ).

Enroll up to 535 patients at up to 75 sites worldwide

and provide up to 5 years of follow-up

Gray Williams et al behalf IMPERIAL trial – Lancet 2018; 392 sep 24

A polymer-coated, paclitaxel-eluting stent (Eluvia) versus a polymer-free, paclitaxel-coated stent (Zilver PTX) for

endovascular femoropopliteal intervention (IMPERIAL): a randomised, non-inferiority trial

Gray Williams et al behalf IMPERIAL trial – Lancet 2018; 392 sep 24

FDA finds 50% higher risk of 5-year mortality with paclitaxel PAD productsMarch 15, 2019

The FDA’s own preliminary analysis included three trials with at least five years of follow-up data.

“While the analyses are ongoing, our preliminary review of this data has identified a potentially concerning signal of increased long-term mortality in study subjects treated with paclitaxel-coated products compared to patients treated with uncoated devices,” the agency stated. “In total, among the 975 subjects in these 3 trials, there was an approximately 50% increased risk of mortality in subjects treated with paclitaxel-coated devices versus those treated with control devices (20.1% versus 13.4% crude risk of death at 5 years).”

The FDA acknowledged pooling the studies may lead to a “greater uncertainty in the results” and said the specific cause and mechanism of the higher mortality rates is unknown. Nevertheless, the agency said it would convene an advisory committee meeting of its Circulatory System Devices Panel to discuss those potential mechanisms, facilitate a discussion on the long-term mortality signal, consider modifications to U.S. clinical trials of paclitaxel products and re-examine the benefit-risk profile for these devices.

The Leipzig Interventional Course - January 2019

The Leipzig Interventional Course - January 2019

REAL PTX (Randomized Evaluation of the Zilver PTX Stent vs. Paclitaxel-Eluting Balloons for Treatment of Symptomatic Peripheral Artery Disease of

the Femoropopliteal Artery) studyProspective randomized controlled trial including 150 patients with symptomatic femoropopliteal arterial disease (Rutherford category 2 to 5) centers located in Germany and Belgium.De novo or restenotic femoropopliteal lesions not exceeding the medial femoral epicondyle, a lesion length ≤30 cm, and at least 1 patent tibial runoff vessel.

Yvonne Bausback, Andrej Schmidt, Thomas Zeller, Marc Bosiers, Dierk Scheinert, Sabine SteinerJ Am Coll Cardiol 2019;73:667–79

REAL PTX (Randomized Evaluation of the Zilver PTX Stent vs. Paclitaxel-Eluting Balloons for Treatment of Symptomatic Peripheral Artery Disease of

the Femoropopliteal Artery) study

Yvonne Bausback, Andrej Schmidt, Thomas Zeller, Marc Bosiers, Dierk Scheinert, Sabine SteinerJ Am Coll Cardiol 2019;73:667–79

REAL PTX (Randomized Evaluation of the Zilver PTX Stent vs. Paclitaxel-Eluting Balloons for Treatment of Symptomatic Peripheral Artery Disease of

the Femoropopliteal Artery) study

Yvonne Bausback, Andrej Schmidt, Thomas Zeller, Marc Bosiers, Dierk Scheinert, Sabine SteinerJ Am Coll Cardiol 2019;73:667–79

Stenotic lesions

Long lesions(>10cm)

Decidir “qué dejar detrás”

DCB: LEVANT 2 IN.PACT GLOBAL STUDYILLUMENATE RCT

Bailout or provitional stent 6% - 21%

“Preparación del vaso”

Insuflaciones prolongadas (varios minutos)Balones no complacientes / balones de corte (cutting balloon)AterótomosLitotrisia intravascular (Litoplastia)

La inevitable necesidad de stent

Tipo de stent: Zilver PTX DES / IMPERIAL (Eluvia DES)

Conclusiones:

Enfermos con arteriopatía periférica: subdiagnóstico y sub tratamiento en comparación con enfermedad coronaria.

Programa conjunto paralelo de actividad física supervisada y revascularización.

Dispositivos endovasculares liberadores de droga (balones y stents) han demostrado su eficacia y durabilidad.

La combinación de tecnologías (debulking seguido por DCB) ofrecen una atractiva alternativa a evaluar.

Procedimiento correcto en el paciente correcto en el momento correcto.

Muchas Gracias