Konstantinos Katsanos, MSc, , EBIR · Konstantinos Katsanos, MSc, MD, PhD, EBIR Associate Professor...

Konstantinos Katsanos, MSc, MD, PhD, EBIR

Associate Professor

Interventional Radiologist

Patras School of Medicine, GR

▪ Research support by Abbott Vascular,

Medalliance & RONTIS

▪ Speaker fees by Abbott Vascular & Concept

Medical

PTX: diterpenoid antineoplastic that blocks cell proliferation by binding to

intracellular tubulin and interfering with spindle formation and disassembly

SRL: immunosuppressant binds to intracellular receptor FKPB12, inhibits

activity of mTOR and arrests cell cycle at the G1 phase

Axel DI, et al. Circulation 1997 – Wessely R, et al. JACC 2006

Matter, CM, et al. J Cardiovasc Phar 2006, Katsanos K, et al. JVIR 2020

PROPERTIES PACLITAXEL SIROLIMUS

CHEMISTRY <1kDa, Solubility 6≈mg/ml <1kDa, Solubility 6≈mg/ml

ACTION CYTOTOXIC CYTOSTATIC

INHIBITION OF SMC + + + + + +

VSMC IC50 ~2.0nM ~4.0nM

APOPTOTIC EFFECTS + + (+)

Endothelial Cell IC50 ~1.0pM (or 0.001 nM) ~1.0nM

IMMUNOSUPPRESIVE (+) + +

VASCULAR DISTRIBUTION ADVENTITIAL PARTITION INTIMA-MEDIA-ADVENTITIA

THERAPEUTIC RANGE NARROW WIDE

RESTENOSIS PATTERN DIFFUSE PROLIFERATIVE FOCAL

SYSTEMIC TOXICITY DEATHS – AMPUTATIONS? SAFE IN CORONARY RCTs

Levin, DA and Edelman, PNAS, 2004

Planar > Transmural

by several orders

Rapamycin

Paclitaxel

Transmural diffusivity

PTX partitions to adventitia

Sirolimus Paclitaxel

Presentation material - Granada J, CRT 2014

PACLITAXEL Risk-Benefit @ 5 yearsFemoropopliteal meta-analysis 2018

Study

Fixed effect model

Random effects model

Prediction interval

Heterogeneity: I2 = 0%,

2 = 0, p = 0.99

IN.PACT SFA

LEVANT II

ZILVER-PTX

THUNDER

FINNPTX

TE

0.40

0.47

0.49

0.51

0.81

seTE

0.3373

0.2488

0.2820

0.4482

0.7128

0.1 0.2 0.5 1 2 5 10

Hazard Ratio HR

1.62

1.62

1.50

1.60

1.64

1.67

2.26

95%-CI

[1.21; 2.17]

[1.21; 2.17]

[1.01; 2.61]

[0.77; 2.90]

[0.98; 2.60]

[0.94; 2.85]

[0.69; 4.01]

[0.56; 9.13]

(fixed)

100.0%

--

19.8%

36.3%

28.3%

11.2%

4.4%

Weight

(random)

--

100.0%

19.8%

36.3%

28.3%

11.2%

4.4%

Weight

Study

Fixed effect model

Random effects model

Prediction interval

Heterogeneity: I2 = 56%,

2 = 0.0668, p = 0.08

LEVANT II

IN.PACT SFA

ZILVER-PTX

THUNDER

TE

-0.13

-0.56

-0.69

-0.97

seTE

0.1931

0.2342

0.2100

0.3136

0.1 0.2 0.5 1 2 5 10

Hazard Ratio HR

0.60

0.58

0.88

0.57

0.50

0.38

95%-CI

[0.48; 0.75]

[0.41; 0.82]

[0.15; 2.22]

[0.60; 1.28]

[0.36; 0.91]

[0.33; 0.76]

[0.20; 0.70]

(fixed)

100.0%

--

34.4%

23.4%

29.1%

13.1%

Weight

(random)

--

100.0%

29.2%

25.0%

27.4%

18.4%

Weight

↓42% TLR

↑62% Death

Methods of Tierney JF, et al. 2007

PACLITAXEL Risk-Benefit @ 1 yearInfrapopliteal meta-analysis 2020

↑52% Death or Amp

↓47% TLR

Paclitaxel distal embolization

J Granada CRFT Zeller et al. JACC 2014

P=0.09

Silva GV, et al. Comparative Healing Response After Sirolimus- and

Paclitaxel-eluting Stent Implantation in a Pig Model. CCIR 2009

Similar endothelialization – PTX significantly higher inflammation scores

PaclitaxelSirolimus

Bisdas T, et al. 1-Year All-Comers Analysis of the Eluvia Drug-Eluting Stent. JACC CI 2018

Coronary RCTs – Sirolimus versus paclitaxel DES: Moliterno NEJM 2005

Abizaid A. Sirolimus-eluting stents VHRM 2007

Pooled late lumen loss (LLL) reported in the FEMPAC, LEVANT I & BIOLUX P-I

Sirolimus results from the SELUTION sirolimus-coated balloon study

COMMENTARY by K Katsanos et al. - JEVT Oct 2020

Femoropopliteal studies

▪ Sirolimus has a more favorable

pharmacological profile than Paclitaxel

▪ Sirolimus has shown more effective anti-

restenotic properties in the coronary arteries

▪ Sirolimus may be an alternative in light of

Paclitaxel safety concerns in the lower limbs

Patras, Rion Bridge, 2004