Konstantinos Katsanos, MSc, , EBIR · Konstantinos Katsanos, MSc, MD, PhD, EBIR Associate Professor...
Transcript of Konstantinos Katsanos, MSc, , EBIR · Konstantinos Katsanos, MSc, MD, PhD, EBIR Associate Professor...
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Konstantinos Katsanos, MSc, MD, PhD, EBIR
Associate Professor
Interventional Radiologist
Patras School of Medicine, GR
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▪ Research support by Abbott Vascular,
Medalliance & RONTIS
▪ Speaker fees by Abbott Vascular & Concept
Medical
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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
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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
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Levin, DA and Edelman, PNAS, 2004
Planar > Transmural
by several orders
Rapamycin
Paclitaxel
Transmural diffusivity
PTX partitions to adventitia
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Sirolimus Paclitaxel
Presentation material - Granada J, CRT 2014
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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
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PACLITAXEL Risk-Benefit @ 1 yearInfrapopliteal meta-analysis 2020
↑52% Death or Amp
↓47% TLR
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Paclitaxel distal embolization
J Granada CRFT Zeller et al. JACC 2014
P=0.09
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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
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Bisdas T, et al. 1-Year All-Comers Analysis of the Eluvia Drug-Eluting Stent. JACC CI 2018
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Coronary RCTs – Sirolimus versus paclitaxel DES: Moliterno NEJM 2005
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Abizaid A. Sirolimus-eluting stents VHRM 2007
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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
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▪ 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
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Patras, Rion Bridge, 2004