Supralimus™ bioabsorbable-polymer

sirolimus-eluting stent technology in

patients with acute coronary syndrome

undergoing percutaneous coronary

intervention: Initial results of the

prospective, international, multicenter, E-

SERIES Registry

TCT 2009

San Francisco, CA

Background - ICRC

Despite the overall marked efficacy of first generation

(FDA approved) drug-eluting stents (DES) on reducing

neointimal hyperplasia and restenosis, and therefore,

the need for repeat lesion revascularization compared

to bare metal stents1,2, concerns regarding

performance, deliverability, and long-term safety –

especially in more complex subsets3,4, has led to the

development of novel DES technologies incorporating

potent antiproliferative agents with alternative stent

platforms and biocompatible drug carrier systems5

1Moses JW et al. N Engl J Med. 2003;349:1315-232Stone GW et al. N Engl J Med 2004;350:221-31

3Lemos PA et al. Circulation 2004;109:1366-704Maisel WH. 2007;356:998-1008

5Dani S et a. 2008;4:59-63

Study DeviceCRC

Supralimus® DES system (Sahajanand Med., Surat, India):

Millenium® (Sahajanand Med., Surat, India) stent platform: 316L

stainless steel, laser cut tubular matrix

Pre-mounted on balloon-expandable device, Rx system

Available in the following measures:

Lengths: 11, 16, 19, 23, 29, 33, and 39 mm

Diameters: 2.25, 2.5, 2.75, 3.0, 3.5, and 4.0 mm

Drug-carrier: multiple layer of biodegradable polymers (4.3 μm

thick), including: Poly L-Lactide, 50/50 Poly DL-Lactide-co-

Glycolide and Polyvinyl Pyrrolidone, and also a top layer

containing drug-free polymeric layer:

Top drug-free protective layer

100% drug-base layer → program-

med for bi-phasic drug release

Antiproliferative AgentCRC

Potent immunosuppressant activity:

Agent used for prevention of rejection in renal and heart transplantation

Reduce smooth muscle cell proliferation in human transplant allografts

Sirolimus (C51H79NO13) – a naturally occuring antimicrobial

(macrolide) compound (Rapamune)

Smooth muscle cell

SignalTransduction

Receptor activation

SMC Proliferation

MigrationMatrix

secretion

TOR

CellCycle

S

G2

M

G0 G1

XThe dosage of Sirolimus in the Supralimus DES is 1.4 µg per mm2 – total drug

dose per stent ranging from 72 µg to 256 µg

Drug Elution CurveCRC

Cumulative Drug Release for Supralimus Sirolimus-

Eluting Stents (SES)

% C

um

ula

tive

Re

lea

se

ObjectiveCRC

To investigate the performance

and clinical impact of the novel

Supralimus ™SES technology in

unselected patients with acute

coronary syndromes (ACS) treated in

the “real-world” clinical practice

Study DesignCRC

Prospective, multicenter, non-randomized, post-marketing

web-based registry to evaluate the impact of the Supralimus

SES for the treatment of coronary lesions in unselected

patients

PIs: Alexandre Abizaid, MD, PhD – Instituto Dante

Pazzanese, São Paulo, Brazil (International PI)

Expedito Ribeiro, MD, PhD – Instituto do Coração,

São Paulo, Brazil (Brazil PI)

Enrollment: since Jan/07 (ongoing), up to 1,500 subjects

Sites: 50 sites in Brazil, Venezuela and India

Clinical follow-up (FU): 1, 6, 12 and 24 months

Data Center: Cardiovascular Research Center, São Paulo,

Brazil

Sponsor: Sahajanand Medical Technologies Pvt. Ltd., Surat,

India

Participant Clinical Sites*CRC

Intercath Meridional, ES, Brazil - 155 pts

Bruno Machado, MD; J. Airton Arruda, MD

Centro Cardiologia Radiologia, GO, Brazil - 146 pts

Alvaro Moraes, MD; Maurício Prudente, MD

CIAS – Unimed Vitória, ES, Brazil - 133 pts

Bruno Machado, MD; J. Airton Arruda, MD

BDM Mahavir Heart Institute, Surat, India - 79 pts

Apurva Vasavda, MD; Atul Abhyankar, MD; Devang Desai, MD; Pritesh Parikh, MD

Hospital São Camilo, SP, Brazil - 68 ptsFábio S. Brito, MD

Instituto Dante Pazzanese, SP, Brazil - 48 ptsFausto Feres, MD

Hospital Luxemburgo, MG, Brazil - 47 ptsCaiser Teixeira, Jr., MD

Hospital Cardiológico Costantini, PR, Brazil - 42 ptsCostantino R. Costantini, MD

Hospital Albert Einstein, SP, Brazil - 39 ptsAlexandre Abizaid, MD; Marco Perin, MD

Int. Assint. Médica Serv. Público, SP, Brazil - 36 ptsAlessandro Pina, MD; George Ximenes, MD

Hospital do Coração do Brasil, DF, Brazil - 29 ptsEdmur Araújo, MD; Luciano Liberato, MD

Hosp. de Clínicas de Caracas, Venezuela - 28 ptsÁlvaro Matheus, MD; César Ochoa, MD; Enrique Fermin, MD; Humberto Casal, MD

Hospital São Camilo Santana, SP, Brazil - 27 ptsFábio Sândoli Brito, MD, PhD

Hosp. Nossa Senhora Graças, PR, Brazil - 22 pts

Álvaro Moura, MD; Lavalle, MD

Hospital São Vicente, PR, Brazil - 20 ptsÁlvaro Moura, MD; Lavalle, MD

Instituto do Coração, SP, Brazil - 20 ptsExpedito E. Ribeiro, MD; Pedro Lemos, MD

Cong. Filhas N. S. Stella Maris, SP, Brazil - 19 ptsAlessandro Pina, MD; George Ximenes, MD; Luciano de Abreu, MD

Hospital Univers. de Caracas, Venezuela - 19 ptsCésar Ochoa, MD; José A. Lopes, MD; Victor Rodriguez, MD

Itaperuna-Conf. S. José Havaí, RJ, Brazil - 18 ptsAntônio C. Botelho, MD

Minas Cor, MG, Brazil - 18 ptsFabiano Cunha, MD; João L. Dias, MD

Hospital Bandeirantes, SP, Brazil - 15 ptsHélio José Castello Jr, MD

Hospital Vita, PR, Brazil - 12 ptsRubens Zenóbio, MD; Viviana Lemke, MD

Unicor, RJ, Brazil - 12 ptsJoão E. Tinoco, MD

Hospital Monte Sinai, MG, Brazil - 11 ptsAntônio J. Muniz, MD; Gustavo Ramalho, MD; João B. Loures, MD

H. C. Unesp Botucatu, SP, Brazil - 10 ptsFábio C. Carvalho, MD

Hosp. Beneficência Portuguesa, SP, Brazil - 10 ptsJosé A. Mangione, MD

H. D. Hernan H. Aravena , Temuco, Chile - 9 ptsChristian P. Jofre, MD

Hosp. Univers. Marília, SP, Brazil - 9 ptsRicardo J. Tofano, MD; Wesley F. Silveira, MD

*Top enrolling clinical centers

Study PopulationCRC

Patients “all comers” for percutaneous coronary

intervention (PCI) with baseline clinical presentation of

ACS (Unstable Angina / non-ST or ST-elevation MI)

>18 years of age

Presence of at least 1 documented stenosis >50% (by

visual estimation) in a native coronary vessel suitable for

PCI with implantation of the Supralimus SES

No pre-specified limitations regarding the number of

lesions/vessels to be treated with the study device

Exclusion criteria:

known illness with life expectancy <12 months;

impossibility to comply with study protocol FUs;

coronary anatomy unsuitable for PCI with stenting

EndpointsCRC

Primary endpoint:

Major adverse cardiac events (MACE) at 12

months clinical FU

Secondary endpoints:

Procedural success

MACE at 30 days, 6 and 24 months clinical

FU

Target lesion revascularization (TLR) at 6

and 12 months

Stent thrombosis up to 24 months FU (FU in

progress)

DefinitionsCRC

Angiographic success: <30% diameter stenosis within the coronary

segment treated with the study device, plus final TIMI 3 flow

Procedural success: angiographic success plus absence of MACE

during hospitalization

Cardiac death: any death due to cardiac cause. Any unwitnessed

death and death of unknown cause, and all procedure-related

deaths, including those related to concomitant treatment, were

classified as cardiac death

Myocardial infarction (MI): Q wave - new pathological Q waves in 2

or more continuous ECG leads with CK-MB levels elevated above

normal and/or positive troponin; non-Q wave - elevated CK≥2 times

the upper limit with the presence of elevated CK-MB and/or positive

troponin in the absence of new pathological Q waves

Target vessel revascularization (TVR): any repeat percutaneous

intervention or surgical bypass of any segment of the target vessel

Major adverse cardiac events (MACE): cardiac death, MI, TVR

Stent thrombosis: according to the ARC* definition*Academic Research Consortium - Cutlip et al. Circulation 2007;115:2344-51

*Academic Research Consortium - Cutlip et al. Circulation 2007;115:2344-51

DEFINITIVE:

ACS:

Angiographic confirmation of stent occlusion;

Anatomic-pathological confirmation of stent occlusion

PROBABLE:

Sudden death within 30 days of PCI

MI in the treated territory despite the angiographic confirmation of stent

thrombosis

POSSIBLE:

Sudden death > 30 days of PCI

Temporal distribution of stent thrombosis:

Acute ≤ 24 h; Sub acute: 24 h-30 d; Late: 30 d-12 m; Very late: > 12 m

Stent Thrombosis Definition

(ARC*)

Patients >18 yo, with at least one coronary lesions ≥

50% treatable with Supralimus™

Fluxogram of the E-Series

Registry

97.9% of clinical FU/ Mean = 13 0.4 months

454 (38.4%)

patients with ACS

Patients consecutively enrolled between

Jan /2007 e Mar/2009

1,181 patientsAnti-platelet therapyPre PCI:AAS: 100 – 500 mgClopidogrel: 300 - 600 mg

Post-procedure:AAS: for goodClopidogrel (75 mg): at least 6 m

ST elevation ACS

(60 pts – 13.2%)

Non-ST elevation

ACS

(394 pts – 86.8%)

Baseline Clinical Demographics

VARIABLE N = 1,181

Age, years 63.3 ± 11.0

Female gender 31,1 %

Hypertension 76,2 %

Diabetes mellitus 36,8 %

Insulin dependent 8,4 %

Dyslipidemia 62,6 %

Current smoking 31,7 %

Family history of CAD 41,8 %

Previous MI (>30 days) 24,4 %

Previous CABG 15,6 %

Previous PCI 30,2 %

Previous CVA 2,0 %

Renal insufficiency (baseline serum creatinine ≥2.0 mg/dL) 6,8 %

CRC

Angiographic Data

VARIABLE N = 454 (504 lesions)

Target lesion located in prox/mid LAD 47.4 %

Moderate/severe calcification 24.6 %

In-stent restenosis 11.7 %

Bifurcation 13.7 %

Significant involvement of both branches 7.4 %

TIMI flow ≤ 1 pre-intervention 12.5 %

Ostial location 3.9 %

Thrombus 6.4 %

SVG 1.4 %

Lesion type B2/C (ACC/AHA classification) 77.3 %

Left ventricule ejection fraction <40% 10.7 %

CRC

Procedural Results

VARIABLE N = 454 (504 lesions)

Staged procedure 2.5 %

Glycoprotein IIb/IIIa inhibitor

use

23.6 %

IVUS guidance 5 %

Multiple stent implantation 18.5 %

Multivessel procedure 10.5 %

Intraprocedural stent

thrombosis

0 %

Final TIMI 3 flow 96.8 %

Angiographic success 96.2 %

CRC

Stent ImplantationVARIABLE N = 592 stents

Predilatation 71.6 %

Nominal balloon length, mm 18.36 ± 5.67

Nominal balloon diameter, mm 2.48 ± 0.41

Maximum inflation pressure, atm 11.8 ± 3.4

Stent implant

Stents per patient 1.22 ± 0.50

Nominal stent length, mm 27.10 ± 8.90

Nominal stent diameter, mm 3.02 ± 0.40

Maximum deployment pressure, atm 13.6 ± 3.1

Postdilatation 46.9 %

Nominal balloon length, mm 14.23 ± 5.64

Nominal balloon diameter, mm 3.20 ± 0.43

Maximum inflation pressure, atm 19.2 ± 4.3

CRC

Quantitative Angiography

Variable (N=504)

Baseline

Lesion length, mm 23.76 ± 10.12

Reference diameter, mm 2.92 ± 0.73

% DS 84.5 ± 10.6

Final

% DS 2.4 ± 5.9

CRC

In-Hospital Clinical OutcomesCRC

% o

f pa

tien

ts

N = 454

Adverse Events up to Months FUCRC

% o

f pa

tien

ts

MACE-Free Survival CurveCRC

Kaplan-Meier

Pts. at risk 454 298 126

Death Events up to 12 MonthsCRC

18 cardiac deaths

7 non-cardiac deaths:

sepsis post non-cardiac surgery (1)

tuberculosis (1)

renal failure (3)

CVA (1)

multiple organ failure (1)

Stent Thrombosis (ARC) up to 12-Mo. CRC

DEFINITE stent thrombosis (ST): 1 cases

Subacute (1-30 days)

PROBABLE stent thrombosis (ST): 2 case

94 days after procedure (late)

Overall DEFINITE + PROBABLE ST = 0.6%

POSSIBLE ST = 4 cases (0.8%)

Overall ST according to all ARC definitions = 1.4%

Follow-up time (up to 12 months) may be limited to

evaluate long-term safety of this novel device. Longer

term results (≥24 m) are warranted;

Other variables like interval time between hospitalization

and PCI as well as adherence to prescribed DAT are

being adjudicated and results will be later available.

LimitationsCRC

ConclusionsCRC

In this prospective, multicenter web-based registry

encompassing a “real-world” population with ACS, the

novel Supralimus sirolimus-eluting stent with a

bioabsorbable polymer demonstrated excellent

performance in high-risk patients with complex coronary

lesions, including high procedural success rate

(>97.5%), and sustained midterm safety

Preliminary clinical results at 12 months demonstrated

clinical effectiveness of the Supralimus technology in

preventing new vessel revascularization, including only

2.7% TVR rate. Also, stent thrombosis

(definite/probable, ARC) rate up to 12 months was <1%

Longer-term FU is warranted