on-Polymeric and Bioabsorbable Polymers on-Polymeric and Bioabsorbable Polymers Will Reign Supreme in Near Future Will Reign Supreme in Near Future Instituto Dante Pazzanese de Instituto Dante Pazzanese de Cardiologia Cardiologia Sao Paulo - Brazil Sao Paulo - Brazil Alexandre Abizaid, MD, PhD, FACC Alexandre Abizaid, MD, PhD, FACC Columbia University Columbia University New York - USA New York - USA
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Non-Polymeric and Bioabsorbable Polymers Will Reign Supreme in Near Future Instituto Dante Pazzanese de Cardiologia Sao Paulo - Brazil Sao Paulo - Brazil.
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Non-Polymeric and Bioabsorbable Polymers Non-Polymeric and Bioabsorbable Polymers Will Reign Supreme in Near FutureWill Reign Supreme in Near Future
Instituto Dante Pazzanese de Cardiologia Instituto Dante Pazzanese de Cardiologia Sao Paulo - BrazilSao Paulo - Brazil
• Fully bioresorbable PLGA polymer (exclusively housed in reservoirs):•Benefits
• Complete resorption in 3-4 months• Fully metabolized• Highly biocompatible and hemocompatible• Future applications could use different co-monomer ratios to permit variable resorption times (few weeks-many months)
Scanning EM of a Genous stent at 48 hours following stenting shows complete coverage of the stents by endothelium (left). The detail (right) shows leucocyte adherence and incomplete cell-cell contact.
Better than any polymer is no polymer…Better than any polymer is no polymer…
• Selectively micro-structured surface holds Selectively micro-structured surface holds drug in abluminal surface structuresdrug in abluminal surface structures
BioFreedomBiosensors Polymer-Free FIM Study (PI: E. Grube)
Symptomatic, Ischemic heart diseaseSymptomatic, Ischemic heart diseaseNative Coronary artery ≥ 2.25 mm and ≤ 3.0 mmNative Coronary artery ≥ 2.25 mm and ≤ 3.0 mmLesion length ≤ 14 mmLesion length ≤ 14 mmLesion amenable to percutaneous treatment with DESLesion amenable to percutaneous treatment with DES
30 d30 d 4 mo 4 mo 12 mo 12 mo 2yr 3yr 4yr 5yr 2yr 3yr 4yr 5yr
Primary Endpoint: In stent Late Lumen Loss (LL) at 12 months (25 patients fromeach cohort will receive angio/IVUS at 4 months, balance 12 months)
Secondary Endpoints: MACE and stent thrombosis rate at 30 days, 6 and 12 months
In-stent/In-segment binary restenosis at 6 monthsIn-stent, prox and dist, LL at 6 monthsNeointimal hyperplastic volume at 6 months measured by IVUS
– Hydrates & erodes through dissolution in body fluids
– DES becomes BMS within 6 months
• Controlled release of drug
• Silica Sol-gel Process:1. Simple molecular precursors are converted into nanometer-sized particles to form a
colloidal suspension, or sol. 2. The colloidal nanoparticles are then linked with one another to form a 3D Network
PLUS-One Study Design
Clinical Follow-up
1 m 4 m 1 y 2 y 3 y 4 y 5 y
de novo lesions in native coronary arteries
RVD: 3.0 mm - 3.75 mm
Lesion length: ≤20 mm
Stent diameters: 3.0 - 3.5 mm Stent length: 12, 18, 24 mm
Dose A: 4 mcg/ 18mm stent (0.03 mcg per mm2); n = 30
Dose B: 8 mcg/ 18mm stent (0.06 mcg per mm2); n = 30
Primary Endpoint4-month MACE event rate, defined as cardiac death, MI (Q wave & non-Q wave), and ischemia-driven TLRSecondary EndpointsLesion, Device & Procedure Success with <30% residual stenosisMACE at Hospital Discharge & 30 days, 1, 2, 3, 4 & 5 years4-Month Diameter Stenosis (%), in-stent and in-segment angiographic late loss (mm) and binary restenosis rate (%) by QCA and 4-month NIH volume by IVUS (mm3)
QCA/ IVUS Follow-up
Clinical Follow-up
Abluminal coating – 5µ thickness applied on
crimped stent.
Consistent coating ensuring 98% of the drug
delivered to the site.
Polymer free Paclitaxel.
2.5µg/mm² dose.
Boost-release (60% in 2 days)
Profile release established in 30 days (98% of the drug)
Back to regular Chromium Cobalt after 45 days.
Abluminal coating – 5µ thickness applied on
crimped stent.
Consistent coating ensuring 98% of the drug
delivered to the site.
Polymer free Paclitaxel.
2.5µg/mm² dose.
Boost-release (60% in 2 days)
Profile release established in 30 days (98% of the drug)
Back to regular Chromium Cobalt after 45 days.
Polymer Free PaclitaxelPolymer Free Paclitaxel
PAX A PAX A (PI: A Abizaid)(PI: A Abizaid)
First In-Man First In-Man randomizedrandomized
n = 30n = 30Taxus LiberteTaxus Liberte
n = 15n = 15
AMAZONIA PaxAMAZONIA Paxn = 15n = 15
Primary Endpoint: Primary Endpoint: Late Loss Late Loss
% obstruction% obstructionOCT tissue OCT tissue coverage coverage
at 4 Monthsat 4 Months
Sub-analysis:Sub-analysis:Sub-analysis:Sub-analysis:•Endothelial function in 30 ptsEndothelial function in 30 pts•Endothelial function in 30 ptsEndothelial function in 30 pts
* 1 pt refused to undergo invasive FU at 9 months and therefore were excluded from this sub * 1 pt refused to undergo invasive FU at 9 months and therefore were excluded from this sub analysis.analysis.
PREPRE POSTPOST
4 MONTH- FU4 MONTH- FU 9 MONTH- FU9 MONTH- FU
Lo
we
r L
LL
(-0
.1
Lo
we
r L
LL
(-0
.1
mm
)m
m)
PRE POST
FOLLOW-UP 4 MONTHS
VESTASYNC II VESTASYNC II Polymer-Free Sirolimus-Eluting Stent
First In-Man First In-Man 3:1 randomized3:1 randomized
First Genaration Durable Polymers First Genaration Durable Polymers with thick polymer loading are being with thick polymer loading are being gradually replaced to more advanced gradually replaced to more advanced technology.technology.
Non-Polymeric DES with surface Non-Polymeric DES with surface modification will dominate the modification will dominate the market.market.
Bioabsorbable Polymers with Bioabsorbable Polymers with abluminal release and reservoir abluminal release and reservoir technology are slowing replacing technology are slowing replacing the first gen DES.the first gen DES.