Ảnh hưởng của các phát kiến, cải tiến trong tim mạch can thiệp đến thực hành lâm sàng

StanfordThree Clinical Needs in New DES • Late Stent Thrombosis • Restenosis of DES • DAPT needs... StanfordThree Clinical Needs in New DES • Late Stent Thrombosis • Restenosis of D

Stanford

Conflict of Interest

• Abbott Medical Advisory Board

• Medtronic Coronary Scientific Advisory Board

• Boston Scientific Executive Physician

Council

Stanford

Three Clinical Needs in New DES

• Late Stent Thrombosis

• Restenosis of DES

• DAPT needs

Stanford

Stanford

Stanford

Three Clinical Needs in New DES

• Late Stent Thrombosis

• Restenosis of DES

• DAPT needs

Serruys PW Presented at TCT 2011

Cumulative LLL in ABSORB Cohort B

and Patients Treated With EES

Durability of Antirestenotic Efficacy

0.5

8.8 9.9

12.8

0 4 8 12 16

30 days 1 year 2 years 3 years

Etiology of DES events beyond 1 year

Very late thrombosis and restenosis

Possible causes

1 Uncovered stent struts (thrombosis)

2 Persistent stimulation of SMCs, from adherent fibrin

and/or loss of normal vessel curvature

3 Abnormal shear stress from protruding struts and/or

loss of cyclic strain relief (compliance mismatch)

4 Chronic inflammation due to late foreign body

reactions and polymer hypersensitivity

5 Positive remodeling with strut malapposition

6 Strut fracture

7 Neoatherosclerosis

Technische Universität München

Polymer Coatings and Arterial Healing

• Most clinically effective durable polymer DES

(Cypher SES, Xience EES, Resolute ZES)*

*Cypher, Xience, Resolute Product information; # Curcio et al Circulation Journal 2011

• PBMA degrades to the

10

Stent designs tested (n=15 for each design)

Vision Multi-Link 8 Element Premier Integrity

n=15 n=15 n=15 n=15 n=15 n=15

Bend cycles to fracture for 6 designs

Ormiston EuroIntervention in press 11

Biomatrix

Fractures were most commonly in connectors especially

curved parts of connectors

12

• When DES struts fracture, there is polymer damage too

• May influence local inflammation and restenosis

• May contribute to neoatheroma

Polymer damage Polymer damage as well as strut fracture

13

Stanford

Stanford

Three Clinical Needs in New DES

• Late Stent Thrombosis

• Restenosis of DES

• DAPT needs

For OMA Distribution Only Trademarks may be registered and are the property of their respective owners © 2013 Medtronic, Inc All Rights Reserved 10116744DOC_1A 10/2013

RESOLUTE Pooled

Timing of Permanently Discontinued DAPT

And ST Through 3 Years

Permanently Discontinued 0-1 Month

Permanently Discontinued 1-12 Months

Permanently Discontinued 12-24 Months

Permanently Discontinued 24-36 Months

# of pts at risk

at baseline 1789 63 594 1806 644

There were only 2 events out to 3 years among patients permanently discontinuing

DAPT after completing one month of DAPT

There were no new ST events between 24 and 36 months

The never interrupted group includes patients who interrupted only after an ST event

Abbott Vascular Confidential, for advisory board

purposes only Do not distribute, reproduce or excerpt

©2013 Abbott All rights reserved

XIENCE Demonstrates 0% Stent Thrombosis Rate After DAPT Interruption from 3 to 12 Months 1

1 Palmerini, T Stent Thrombosis and DAPT Interruption in XIENCE V Real-World Patients PCR 2012

2 Including patients with no DAPT Interruption except possibly after Stent Thrombosis though 365 days

Patients should follow physicians’ guidance for utilization of dual anti-platelet therapy following stent implantation

3 Approaches to Improve Late DES

Outcomes

1 Metallic DES with bioabsorbable polymers

2 Metallic DES, polymer-free

3 Bioresorbable vascular scaffold (BVS)

Strut Thickness 140 µm 132 µm 96 µm 89 µm 81 µm 81 µm Coat Thickness 7µm / side 16µm/side 14µm/side 6µm / side 8µm / side 8µm / side

Liberte

Resolute Integrity

Xience Xpedition

Promus PREMIER

Evolution of DES Technology

Stent

First Generation Future Technologies

Polymer Free Stents

Platelet Accumulation on Stent Surface

PVDF Durable Polymer vs Metallic Surfaces

*

*

*

Eppihimer M, Granada JF, TCT2012

Total Stent Inflammatory Area

Bioabsorbable vs Durable Polymer DES

OMEGA BMS SYNERGY

* p<0.05 vs BMS & SYNERGY

Inflammation at 180 Days in Familial Hypercholesterolemic Swine Model

Abluminal Bioabsorbable PLGA

Mike Eppihimer, PhD, EuroPCR 2014

Bioabsorbable PLGA

Stent Surface and EC Coverage

Abluminal vs Conformal Polymer

% Endothelial Cell (EC) Coverage at 21 Days in Cell Assay

89 RCTs with 85,490 patients

Palmerini et al JACC 2014;63:299-307

Palmerini et al JACC 2014;63:299-307

Limitations of data

…not all BP-DES are equal

Overview of current stent designs

Sources: 1: GG Stefanini, M Taniwaki, S Windecker, Coronary stents: novel development, Heart 2013; 2: IT Meredith, Scientific symposium, TCT 2013

Strut and coating thickness in perspective

Overview of current stent designs

Sources: 1: GG Stefanini, M Taniwaki, S Windecker, Coronary stents: novel development, Heart 2013; 2: IT Meredith, Scientific symposium, TCT 2013

Strut and coating thickness in perspective

D AYS SINCE INDEX PROCEDURE

B IO S CIENCE : P RIMARY ENDPOINT - T ARGET LESION FAILURE

A BSOLUTE RISK DIFFERENCE -0.14%, UPPER LIMIT OF ONE - SIDED 95% CI 1.97%

BIOSCIENCE

Piligrim et al Lancet 2014; online

2 2.2 2.4 2.6 2.8 3 3.2 3.4

meanldia_stent_vas3 meanldia_stent_vas2 meanldia_stent_vasfp

Ergonovine (n=13) 2.63±.19 2.47±.21 2.67±.20 P<0.001 p=0.001

Pre Met Nitro

Shielding of plaque

Absorb BVS and neointimal formation

Serial OCT examinations in 20 patients

Sealing and shielding of plaques as a result of scaffold implantation : can the scaffold cap the plaque?

* * *

Gene Expression: Absorb BVS Smooth Muscle Cell Phenotype Markers

*

p= 7.06E-04

• Multiple early markers of SMC differentiation [e.g smooth muscle actin

(SMA) and tropomyosin (TPM )1, 2, 3, 4] have been recovered, while

several late markers [desmin (DES), calponin 1 (CNN1), smoothelin

(SMTN)] have not recovered Indicating that the smooth muscle cells are in a transitional phase

• The up-regulation of iNOS may indicate that the synthetic, non-contractile SMCs are expressing nitric oxide synthase (NOS) and NO, in order to

compensate for the inability to properly communicate with the ECs 6

At one year in the porcine model

Min lumen area in cohort B1 Min lumen area in cohort B2 Neointimal area in cohort B1 Neointimal area in cohort B2

OCT including pre TLR measurement

Strut Thickness 140 µm 132 µm 96 µm 89 µm 81 µm 81 µm Coat Thickness 7µm / side 16µm/side 14µm/side 6µm / side 8µm / side 8µm / side

Liberte

Resolute Integrity

Xience Xpedition

Promus PREMIER

Evolution of DES Technology

Stent

First Generation Future Technologies

Polymer Free Stents

Fantom is Completely Visible Under X-Ray

• Fantom’s complete (x-ray) visibility

increases confidence during the

procedure

– Precise scaffold placement

– Complete lesion coverage

– Saving costs to hospital

• No permanent metal markers left

behind

Absorb Fantom Xience

Fantom

Which patients?

The European Multicenter GHOST-EU Registry – Vers 1.2

Capodanno et al, GHOST-EU Investigators – EuroIntervention 2014

*Compared to ABSORB II eligibility (Diletti et al Am Heart J 2012;164:654-63)

CTO, N=96/1,440(6.7%) Ostial, N=90/1,282 (7.0%) ISR, N=49/1,440 (3.4%) CKD (eGFR<60), N=111/743 (14.9%)

LVEF<30%, N=32/980 (3.3%) NSTEMI/STEMI, N=406/1,189(34.1%)

The European Multicenter GHOST-EU Registry – Vers 1.2

Capodanno et al, GHOST-EU Investigators – EuroIntervention 2014

CV Death All-Cause

Death

vessel MI

Clinically-driven TLR

driven TVR

*Event rates are expressed as Kaplan Meier estimates

** Device-Oriented composite primiry endpoint

The European Multicenter GHOST-EU Registry – Vers 1.2

Capodanno et al, GHOST-EU Investigators – EuroIntervention 2014

1.5%

Absorb II, 501 patients / 546 lesions

Data

COMPARE ABSORB trial

Comparison between ABSORB and

Xience in a high risk population for TLF

filling the gap in evidence in lesions / patients not included in the randomised ABSORB trials

COMPARE ABSORB trial: Randomization

at 5Y (or 7Y)

2 nd analysis:

Superiority in TLF between 1 and 5

years

• BP-DES or Polymer-free DES could

provide such outcome

• BRS could also provide such long term durability

• Better characterization of acute BRS ST risk will be crucial