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Orsiro - Hybrid Drug Eluting Stent Clinical Update Dr Michael Nguyen Da Nang 12 Oct 2014 BIOTRONIK // Vascular Intervention... Randomised comparison of a novel, ultrathin strut biodegrad

Orsiro - Hybrid Drug Eluting Stent Clinical Update

Dr Michael Nguyen

Da Nang 12 Oct 2014

BIOTRONIK // Vascular Intervention

Perth, Western Australia

Fiona Stanley Hospital

Updated Orsiro movie to promote BIOSCIENCE results available on Orsiro.com and via e-Blast

Randomised comparison of a novel, ultrathin

strut biodegradable polymer sirolimus-eluting stent with a durable polymer everolimus-eluting stent for percutaneous coronary

revascularization

 Thomas Pilgrim, MD; Dik Heg, PhD; Marco Roffi, MD; David Tüller, MD;

 Olivier Muller, MD; André Vuilliomenet, MD; Stéphane Cook, MD;

 Daniel Weilenmann, MD; Christoph Kaiser, MD; Peiman Jamshidi, MD;

 Bernhard Meier, MD; Peter Jüni, MD; Stephan Windecker, MD

 Department of Cardiology, Swiss Cardiovascular Center, University Hospital, Bern;

Institute of Social and Preventive Medicine and Clinical Trials Unit

 Bern University Hospital, Switzerland1

NCT01443104

Antiproliferative drug

Sirolimus-analogues

Paclitaxel

Durable polymer Biodegradable polymer

Polymer material

132 140 120 91 87 81 91 74 60 81 100 64 80 (μm)

Platform material & strut thickness

SES BES ZES SES EES ZES EES SES NES SES SES SES

D URABLE POLYMER EVEROLIMUS - ELUTING STENTS REDUCE THE

Baber U et al J Am Coll Cardiol 2011;58:1569-77

Meta-analysis of 17 RCTs with 17,101 patients and mean follow-up of 22 months

Definite stent thrombosis Target vessel revascularization

Stefanini GG et al, Eur Heart J 2012;33(10):1214-22

B IODEGRADABLE POLYMER DES REDUCE THE RISK OF

DEFINITE ST AND TLR COMPARED TO FIRST GENERATION DES

32/850 9/652 2/202

0.62 (0.36-1.08) 0.50 (0.20-1.26) 0.50 (0.05-5.47)

1

Favours biodegradable polymer DES

Favours durable polymer SES Risk ratio

BP DES DP SES RR (95% CI)

Overall (I 2 = 0.0%, p=0.79)

LEADERS ISAR-TEST 4 ISAR-TEST 3

0.84 (0.71-0.99)

88/857 168/1299 17/202

111/850 95/652 21/202

0.79 (0.60-1.02) 0.89 (0.70-1.12) 0.81 (0.44-1.49)

Favours durable polymer SES

 To compare the safety and efficacy of a novel,

ultrathin strut, biodegradable polymer based sirolimus-eluting stent with a thin strut,

durable polymer everolimus-eluting stent for percutaneous coronary revascularization

The hybrid structure:

 Passive PROBIO silicon carbide

barrier encapsulates device,

eliminating interaction between

stent and the surroundings

 Active BIOlute contains

bioabsorbable PLLA polymer

combined with Limus drug (1.4

µg/mm2)

 Underlying PRO-Kinetic Energy

Stent

Combination of passive and active components

Orsiro Hybrid DES with a bioabsorbable polymer

T RIAL DESIGN

Patients with stable CAD or ACS undergoing PCI

1:1 Randomisation Biodegradable polymer

sirolimus-eluting stent

n = 1,030

Durable polymer everolimus-eluting stent

n = 1,030

Composite of cardiac death, target vessel myocardial infarction, and

clinically-indicated target lesion revascularization at 12 months

Death, cardiac death, myocardial infarction, TLR, TVR, definite ST, definite

Clinical follow-up at 30 days and 12 months

E LIGIBILITY FOR PATIENT ENROLLMENT

 Pregnancy

 Planned surgery within 6 months of

PCI

 Intolerance to aspirin, clopidogrel,

heparin, sirolimus, everolimus, contrast material

 Inability to provide informed consent

 Participation in another trial

Exclusion criteria

• Age ≥ 18 years

• Coronary artery disease

- stable CAD, silent ischemia

- acute coronary syndromes:

UA, NSTEMI, and STEMI

• At least one lesion with diameter

stenosis >50% in a native coronary

artery or a bypass graft

- no of vessels: no limitation

- no of lesions: no limitation

- lesion length: no limitation

Inclusion criteria

Investigator City Patients

2,119 patients were enrolled across 9 centers in Switzerland

Geneva

Lausanne

Fribourg Bern

P ATIENT FLOW

2,129 patients randomised

2,119 patients included

10 provided preliminary consent but refused definite consent

1,063 allocated to biodegradable

polymer sirolimus-eluting stent

(1,594 lesions)

1,056 allocated to durable polymer everolimus-eluting stent

(1,545 lesions)

1,031 follow-up information for

primary endpoint available

1,036 follow-up information for primary endpoint available

1,056 analysed for primary

clinical endpoint

- 20 censored at timepoint of refusal or loss to follow-up

1,063 analysed for primary

clinical endpoint

- 32 censored at timepoint of refusal or loss to follow-up

B ASELINE CHARACTERISTICS BP SES (n=1,063) DP EES (n=1,056)

A NGIOGRAPHIC CHARACTERISTICS BP SES (n=1,594) DP EES (n=1,545)

0 1 2 3 4 5 6 7 8 9

P NON-INFERIORITY = 0.0004

6.7% - BP SES

6.7% - DP EES

Rate ratio = 0.99 (95% CI 0.71-1.38), p=0.95

0 1 2 3 4 5 6 7 8 9

Rate ratio = 0.99 (95%CI 0.71-1.38), p=0.95 0

S TENT THROMBOSIS

D EFINITE STENT THROMBOSIS

0.9% vs 0.4% ; RR 2.26 (95% CI 0.70-7.33), p=0.16

DEFINITE STENT THROMBOSIS

BP SES DP EES RR (95% CI) p p interaction

21/229 49/827

1.19 (0.67-2.10) 0.88 (0.58-1.33)

0.56

0.55

0.41

32/577 37/486

38/554 32/502

0.81 (0.51-1.30) 1.21 (0.75-1.95)

0.39

0.43

0.24

7/211 62/852

17/196 53/860

0.38 (0.16-0.91) 1.20 (0.83-1.73)

0.024 0.33

0.014

43/629 24/427

51/646 19/407

0.87 (0.58-1.31) 1.23 (0.67-2.24)

0.50

0.51

0.35

12/245 57/818

20/240 50/816

0.59 (0.29-1.21) 1.15 (0.79-1.68)

0.15

0.47

0.104

18/151 50/857

18/130 43/865

0.88 (0.45-1.70) 1.19 (0.79-1.79)

• Missing information on patients assessed for

eligibility, but not included into the trial

• The trial was powered for the primary composite

outcome but not individual components

• The primary endpoint results were determined at

12 months precluding conclusions regarding the

long-term safety and efficacy

• One third of patients had undergone previous PCI

and some adverse events may have been related to previously implanted devices

M ETA - ANALYSIS OF BIOSCIENCE AND BIOFLOW II

Target lesion failure

0.95 (0.71-1.27)

19/298 69/1,063

12/154 70/1,056

1.03 (0.09-11.31)

0.90 (0.50-1.64)

0.91 (0.51-1.63)

2/298 20/1,063

1/154 22/1,056

1.03 (0.32-3.38) 0.96 (0.59-1.58)

0.97 (0.62-1.53)

8/298 30/1,063

4/154 31/1,056

0.74 (0.29-1.90) 1.51 (0.90-2.54)

1.18 (0.61-2.30)

10/298 35/1,063

7/154 23/1,056

Risk ratio (95% CI)

BIOSCIENCE confirms the findings of BIOFLOW-II in a large more complex patient population Especially for the hard endpoints Death and MI

• Ultrathin strut biodegradable polymer

sirolimus-eluting stents were non-inferior to durable

polymer everolimus-eluting stents for the primary endpoint target lesion failure at 1 year in a

population with minimal exclusion criteria

• The observed benefit in the subgroup of patients

with ST-segment elevation myocardial infarction warrants confirmation in appropriately designed studies

The Lancet, published online

Personal Experience

Australia Long lengths available up to

40mm

deliverability, ease of use and emerging

efficacy and safety data

Diffuse, tortuous and calcified LAD 3.0 x 26mm stent had no difficulty delivering to mid LAD