Transcript DES vs BMS

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‫ن ا ْلعْلم إّل َلَليال‬
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‫سورة اإلسراء آيه ‪85‬‬
DES versus BMS
Clinical applications
Hany Hassan Ebaid
2009
DES vs BMS
Background
What are DES?
Why DES?
Problems of DES
DES, special situations
What should we do now…?
DES vs BMS
Background
What are DES?
Why DES?
Problems of DES
DES, special situations
What should we do now…?
\
CAD is the #1 cause of Mortality and
Morbidity in the US
The most important advances in the
treatment of CAD have been….
Drugs
ASA (25%
B-Blockers (20%
)
)
Statins (20-35%
)
ACE-I (20%
)
Cardiac Surgery
Benefit over medical therapy in some patients
This field continues to advance…..
BUT no field has advanced more
rapidly than…..
Percutaneous Coronary Intervention
(PCI)
History of
Interventional Cardiology
1977
2009
Evolution of PCI
1844
Bernard coins
the term
“cardiac
catheterization”
1958
Sones discovers
the diagnostic
coronary
angiogram
1929
Forssmann
peforms the 1st
human cardiac
catheterization
1964
Dotter
introduces
transluminal
angioplasty
1962
Ricketts and
Abrams use the
percutaneous
approach in
coronary
arteries
1994
coronary
stent approved
by the FDA
Today
Increasing realworld use of PCI
in LM and 3VD
1st
1977
Gruentzig
peforms the 1st
PTCA
1967
Judkins perfects
the transfemoral
approach
1986
Sigwart and Puel
implant the 1st
coronary stent
2003
FDA approval of
1st DES
2002
CE Mark on 1st
DES
2006
FDA panel on
the safety of
DES
Coronary Angioplasty (PTCA) Andreas
Gruntzig(1977)
History of stents
Early 1990s: Bare-metal stents
were first used
2003: Cypher (sirolimus-eluting)
stent introduced in the US
2004: Taxus (paclitaxel) stent
introduced
Fuster
Ideally, PCI should be….
Safe (no complications)
Effective (improves QOL and survival)
Predictable (consistent results)
Widely applicable (to all anatomy)
Durable (no restenosis)
DES vs BMS
Background
What are DES?
Why DES?
Problems of DES
DES, special situations
What should we do now…?
What are DES?
**Drug-eluting stents (DES) were
introduced into clinical practice in
2002, in order to reduce restenosis
that occurred in 15–25% of patients
receiving bare-metal stents (BMS)
**They are stents loaded with drugs
that interfere with pathways in the
process of inflammation and
neointimal proliferation.
Components of DES
Stent Platform
Drug
Polymer Drug
Carrier
Several types of DES have
been
introduced in clinical practice
They are named according to the drug
used:
Sirolimus DES
Everolimus DES
Biolimus DES
Zotarolimus DES
Tacrolimus DES
pimecrolimus DES
&Paclitaxel DES
Commercial Drug-eluting Stents Systems
Polymer
Sirolimus
PEVA + PBMA blend
Stent
Cypher
Drug
TAXUS
BX Velocity
Endeavor
Paclitaxel
Polyolefin derivative
Express2
DES vs BMS
Background
What are DES?
Why DES?
Problems of DES
DES, special situations
What should we do now…?
The DES euphoria
“drug”eluting
“just” bare metal
Why DES?
DES has been introduced to
overcome the problem of instent restenosis
In-stent restenosis (ISR)
defined by a 50% reduction in
the in-stent luminal diameter
results from primarily neointimal
proliferation.
Instent Restenosis
Restenosis
Occurs in 30-40% of patients by 6
months after PTCA
Occurs in 20-30% of patients by 6
months after PTCA with BMS
Restenosis is thought secondary to
combination of vessel wall remodeling
and neointimal hyperplasia with
smooth muscle cell and matrix
proliferation
Elastic recoil and thrombosis may
also play a role
Restenosis
Elastic recoil: after balloon deflation, the
large number of elastic fibers in the tunica
media cause a mechanical collapse.
Neointimal proliferation (NI): formation of
an inner layer at the site of injury,
composed of cells and ECM on the intimal
surface
Negative remodeling: constriction of the
vessel by the formation of a fibrotic scar
within the adventitia.
Durability (restenosis) has been problematic until the
introduction of Drug Eluting Stents
Restenosis Rate (%)
40
35
PTCA
30
25
20
15
Stent
10
5
0
DES
Preventing Restenosis
DES
Drug-eluting stents (DES) can deliver
anti-proliferative therapy to the target
area without systemic toxicity
inhibit neointimal hyperplasia
Combined with biologic polymers,
drugs are loaded onto the stent which
allows a sustain release
Clinical Trials – DES v. BMS
***Major adverse cardiac events (MACE) were defined as death,
acute myocardial infarction, target lesion revascularization (TLR).
Clinical Trials – DES v. BMS
Restenosis: angiographic evidence of 50% decrease in
luminal diameter
Clinical Trials – DES v. BMS
Clinical Trials – DES v. BMS
Clinical Trials – DES v. BMS
The overall occurrence of MACE was
reduced from 19.9% to 10.1% (p<0.001)
and adjusted rates of angiographic
restenosis from 31.7% to 10.5% (p<0.001)
with DES.
Furthermore, there was no difference in
overall rates of mortality (DES: 0.9%, BMS:
1.2%, p = 0.92), or stent thrombosis (DES:
1.0%, BMS: 0.9%, p = 0.44) between DES
and BMS groups.
FDA Approves!
Cypher & Taxus
The CYPHER Sirolimus-eluting Coronary Stent is
indicated for improving coronary luminal diameter
in patients with symptomatic ischemic disease due
to discrete de novo lesions of length ≤ 30 mm in
native coronary arteries with reference vessel
diameter of ≥2.5 mm to ≤3.5 mm.
The TAXUS Express Paclitaxel-Eluting Coronary
Stent System is indicated for improving luminal
diameter for the treatment of de novo lesions ≤28
mm in length in native coronary arteries ≥2.5 to
≤3.75 mm in diameter.
Stent Wars: SES v. PES
There is no difference in mortality or
myocardial infarction between the
DES.
There is a significant improvement in
angiographic results in SES group.
There appears to be a significant
increase in stent thrombosis in PES
group at 30 months.
DES vs BMS
TAXUS IV
SIRIUS
40%
Overall
Restenosis
(insegment)
36.3%
35%
30%
26.6%
25%
20%
15%
10%
8.9%
7.9%
5%
T=Paclitaxel
S=Sirolimus
0%
T
Control
S
Control
Long term outcome with
drug eluting stents vs.
bare metal stents in Sweden
SCAARSwedish Coronary Angiography
and Angioplasty Registry
www.ucr.uu.se
•National registry 1989-2007 with all
procedures in Sweden.
•In the data base:
294 000 procedures, 123 000 PCI
118 000 stents ( > 37 000 DES)
Complete long-term follow up by merging
with National registries of MI, CABG,
hospital care and death.
Conclusions
During 4 years follow-up the DES-group compared to the
BMS-group, with adjustment for differences in available
background characteristics, showed:
no overall significant difference in mortality or myocardial
infarction
a significantly lower event rate during the initial 6 months
a significantly higher event rate after 6 months which is
compensated by the lower early event rate
An relative reduction of restenosis by almost 50%
corresponding to an absolute reduction of 3.5%
SCAAR
UCR
SWEDEN
2006
DES vs BMS
Background
What are DES?
Why DES?
Problems of DES
DES, special situations
What should we do now…?
Your trials are biased !!!!
Enough is enough !!
Here comes
the
interventional
cardiologist !
A friendly discussion….
The main problem as noticed with
DES is late stent thrombosis which
decrease the early benefit of
reduction of ISR
Time Frame of Stent Thrombosis
1 month
1 year
Early < 1 mo
Late > 1 mo < 1year
Very Late > 1year
Acute Subacute
≤1d >1d - ≤1mo
0 day
>1 day
>1 month
to 1 day
to 1 month
to 1 year
> 1 year
Acute stent thrombosis
Subacute stent thrombosis
Late stent thrombosis
Very late stent thrombosis
Stent Thrombosis – A Real Concern?
Clinical Study N
Conclusions
Bavry et al.
incidence of very late stent thrombosis was 4-5
higher for DES (p = 0.02).
6675
Nordmann et al 8221
No differences in stent thrombosis between
DES and BMS groups.
Stone et al
5261
4-year rates of stent thrombosis were similar
between DES and BMS groups. Between
years 1 and 4 both DES were associated with
significantly higher rates of stent thrombosis
(SES 0.6% vs BMS 0%; p = 0.025 and PES
0.7% vs BMS 0.2%; p = 0.028)
Daemen et al
8146
late thrombosis with PES was higher than with
SES (PES: 1.8%, SES: 1.4%; p = 0.03).
Lagerqvist et al 19771 6-months: trend towards lower stent
thrombosis with DES. After 6-months, DES
had higher rates of stent thrombosis (p = NS).
Late stent thrombosis—
DES: Factors to consider
Discontinuation of
antiplatelet therapy
Delayed
endothelialization
Late stent
thrombosis
Polymer hypersensitivity/
inflammation
Late incomplete
apposition
Early Discontinuation of Anti-platelet Therapy is
one of the Strongest Risk Factors for ST
29.0%
Incidence (%)
Overall stent thrombosis = 1.3% (P=0.09, N=2229)
8.7%
6.2%
1.4%
2.0%
Unstable
angina
Thrombus
Iakovou et al. JAMA. 2005;293:2126.
2.5%
3.3%
3.6%
Diabetes Unprotected left Bifurcation
main
Renal
failure
Prior
brachy Rx
Premature
antiplatelet
discont’d
Results: Predictors of inappropriate
clopidogrel use
Predictors
OR (95% C.I)
Age
0.97 (0.97-0.98)
Female gender
0.79 (0.69-0.91)
Diabetes
1.2 (1.0-1.4)
Medicare insurance
1.5 (1.26-1.81)
DES vs BMS
Background
What are DES?
Why DES?
Problems of DES
DES, special situations
What should we do now…?
DES in special situations
DES in AMI
DES in NSTEMI
DES in unprotected LM lesions
DES in DM
DES in CTO
DES in In-stent restenosis
DES in saphenous vein graft
DES Use
AMI
Left main
Chronic renal failure
Bifurcation
Calcification
Diabetes
“REAL WORLD”
Diffuse disease
Multistenting
Saphenous graft
Multivessel
Ostium
Unstable angina
Thrombus
Long lesions
CTO
DES in special situations
DES in AMI
DES in NSTEMI
DES in unprotected LM lesions
DES in DM
DES in CTO
DES in In-stent restenosis
DES in saphenous vein graft
Drug-eluting stents in acute
myocardial infarction
DES in AMI (RCTs)
Trial
TYPHOO
N*
DES/BMS
SES/Any
N
1º Endpt
Angio
follow-up
700
12 mo TVF
Yes
174 pts
12 mo
cardiac death,
MI, TLR
No
PASSION†
PES/Exp &
Lib
620
SESAMI‡
SES/BxV
320
STRATEG
Y§
SES/BxV
175
12 mo
restenosis
8 mo death,
MI,
CVA, TVR
Yes
Yes
TYPHOON – summary
Use of SES provided significant reduction in
TVR at 12 mo
Similar rates of stent thrombosis
•
only 12-mo follow-up
•
late thrombosis may have been underestimated and
early thrombosis overestimated
Spaulding C et al. N Engl J Med 2006;355:1093-104.
SESAMI – summary
At 1 Year
clinical endpoints (TLR, TVR, TVF and
MACE) significantly better in the SES
group
12-month ST rates were similar between
groups
these data confirm and extend results of
TYPHOON trial due to broader inclusion
criteria.
Menichelli M et al. J Am Coll Cardiol 2007;49:1924-30.
PASSION: summary
Failed to show a significant benefit with the
use of PES vs BMS
Lack of angiographic follow-up may have
contributed to the findings
No difference in ST between the groups
•
only 12 mo data
Laarman GJ et al. N Engl J Med 2006;355:1105-13.
Pasceri et al meta-analysis
Meta-analysis of 7 trials (STRATEGY,
PASSION, TYPHOON, SESAMI, HAAMU-Stent,
MISSION )
that compared DES to BMS in AMI from 2001 –
2006
2357 patients (1177 DES & 1180 BMS) with a
follow-up of 8 – 12 months
Pasceri V et al. Amer Heart J 2007;153:749-54.
Pescari et al – conclusions
In patients with AMI, DES:
can significantly reduce the need
for revascularization
provide no benefit in terms of death or MI
have a similar stent thrombosis rate out
to 1 year
Pasceri V et al. Amer Heart J 2007;153:749-54.
MIDAS TRIAL
METHODS
THE ANALYSIS INCLUDED AMI PATIENTS WITH
STENTS IMPLANTED DURING PCI IN THE YEARS 2003
AND 2004
11,972 INDEX PCI PATIENTS WERE IDENTIFIED
5588 STEMI
5804 NSTEMI (SUBENDOCARDIAL, 410.71)
580 Other and Unspecified by ICD code
DATA ON SURVIVAL WERE OBTAINED BY MATCHING
THE MIDAS RECORDS WITH THE NEW JERSEY DEATH
REGISTRATION FILES.
CONCLUSIONS
MIDAS DATA RECORDS FROM 2003 and 2004 SHOW
THAT THE USE OF DRUG-ELUTING STENTS IN THE
SETTING OF ST-ELEVATION MYOCARDIAL INFARCTION
WAS SIGNIFICANTLY ASSOCIATED WITH REDUCTIONS
OF 3-YEAR ALL CAUSE AND CARDIOVASCULAR
MORTALITY OVER BARE METAL STENTS.
On the other hand
GRACE registry
Observational registry to determine
outcomes for STEMI patients given DES or
BMS
Mortality between 6 mo and 2 years for DES
and BMS were 8.6% and 1.6% respectively
DES should be used with caution in patients
with STEMI
DES in special situations
DES in AMI
DES in NSTEMI
DES in unprotected LM lesions
DES in DM
DES in CTO
DES in In-stent restenosis
DES in saphenous vein graft
Decline in the Use of Drug-Eluting Stents for
Patients With NSTEMI Undergoing PCI: Results
From the CRUSADE and ACTION Registries
Matthew T. Roe, Christopher P. Cannon, Anita Y. Chen,
Sunil Rao, John Rumsfeld, Lloyd Klein, E. Magnus
Ohman, W. Brian Gibler, Eric D. Peterson on behalf of
the CRUSADE and ACTION Registry Participants
Trends in DES vs. BMS Use for PCI for NSTEMI
%
100
90
80
70
60
50
40
DES
DES Debate Begins
FDA Advisory Panel
30
20
10
0
Q1 06 Q2 06 Q3 06 Q4 06 Q1 07 Q2 07 Q3 07 Q4 07
BMS
Conclusions
• Public debate regarding the risks of stent
thrombosis with DES was associated with a rapid
and sustained decline in the proportion of NSTEMI
patients undergoing PCI who received a DES – an
“off label” indication
• The magnitude and duration of this temporal
change in DES use is still being assessed
DES in special situations
DES in AMI
DES in NSTEMI
DES in unprotected LM lesions
DES in DM
DES in CTO
DES in In-stent restenosis
DES in saphenous vein graft
DES in Unprotected Left
Main Coronary Artery
Current (AHA/ACC) and (ESC) guidelines
consider the presence of a stenosis in the
unprotected left main coronary artery
(LMCA) a class IIa or IIb indication,
respectively, for PCI if coronary artery
bypass grafting (CABG) is not a viable
option
Moreover, according to the AHA/ACC
guidelines, in cases when the patient is
eligible for CABG, PCI has a class III
indication.
Recently, encouraging results have
been reported in some observational
registries with elective DES
implantation in LMCA, with a 1-year
mortality of 0% to 5% in these
patients.
DES in special situations
DES in AMI
DES in NSTEMI
DES in unprotected LM lesions
DES in DM
DES in CTO
DES in In-stent restenosis
DES in saphenous vein graft
Drug Eluting and Bare Metal
Stenting for Diabetes Mellitus
Results from the
Massachusetts Data Analysis
Center Registry
Conclusions
In a propensity matched analysis of
2952 Diabetic patients treated with
DES or BMS, there were decreased
rates of death, MI, and TVR
associated with DES at 3 years
This population-based analysis shows
preserved efficacy of DES with no
increased hazard of death and MI
compared with BMS in long term
follow-up
DES in special situations
DES in AMI
DES in NSTEMI
DES in unprotected LM lesions
DES in DM
DES in CTO
DES in In-stent restenosis
DES in saphenous vein graft
The SICTO Study
TM
CYPHER Sirolimus-eluting stent
in Chronic Total Occlusion
Chaim Lotan MD
TCT 04 – Drug Eluting Stent Summ
SICTO – Study Design
 25 patients (72% males, aged 63.1±9.8 years)
were treated between March and July 2003 with
the CYPHERTM Sirolimus-eluting stent after
successful balloon angioplasty and IVUS
examination.
 Clinical follow-up at 30 days, 6, 12, 18 and 24
months. Repeat angiography and IVUS at 6
months follow-up
SICTO – Conclusions
In this feasibility study the CYPHERTM
Sirolimus-eluting stent was very safe and
effective in the treatment of CTO, with 4% TLR
and 12% TVR, compared to historical data with
bare stents
(30-50% restenosis/reocclusion rates).
The CYPHERTM Sirolimus-eluting stent
significantly inhibits intimal hyperplasia in CTO.
These preliminary data confirm real life data
in larger database with CTO subpopulation
(e.g. e-Cypher : n=415; MACE=3.1% [6 months]).
DES in special situations
DES in AMI
DES in NSTEMI
DES in unprotected LM lesions
DES in DM
DES in CTO
DES in In-stent restenosis
DES in saphenous vein graft
TROPICAL
Overview
Multicenter (11 sites / 162 patients); Europe; non-randomized,
prospective study in patients with in-stent restenosis in native
coronary artery lesions< 45 mm in length; > 2.5 mm < 3.0 mm;
CYPHER® Stent; Historical control with GAMMA I/II clinical
outcomes
PI: Neumann (Germany)
Follow up:
6-month angiographic follow up
1 and 9-month, 1, 2, and 3 year clinical follow up
IVUS substudy (6 sites)
Primary Endpoint
Angiographic in-lesion late loss at 6-month post-procedure (QCA)
TROPICAL Conclusions
 In the treatment of in-stent restenosis, sirolimus-eluting
stents were highly efficacious
 Compared with the previous gold standard in the
treatment of in-stent restenosis, brachytherapy,
sirolimus-eluting stents reduced angiographic
restenosis and need for target lesion revascularisation
substantially
 The risk of peri-interventional infarction and of stent
thrombosis was as low as expected with bare stents
ISAR-DESIRE Trial
Study Design
Comparative Trial
Independent, randomized trial:
100 CYPHER vs 100 TAXUS vs 100 PTCA
PI: A. Kastrati (Germany)
Population
RVD – 2.61 mm ; MLD post – 2.39 mm
Lesion Length – 14.1 mm
Diabetic patients – 31% mm
ISAR-DESIRE Trial:
Conclusions
In patients with in-stent restenosis, a strategy based
on DES (Cypher or Taxus) is superior to plain balloon
angioplasty for the reduction of recurrent restenosis.
But the results of Cypher and Taxus for in-stent
restenosis are less remarkable than those for de-novo
lesions suggesting the need for modified doseregimen.
In this high-risk subset for restenosis, the use of
sirolimus-eluting stents (Cypher) has the potential of a
greater benefit than the use of paclitaxel-eluting stents
(Taxus)
Kastrati, ESC 2004
DES in special situations
DES in AMI
DES in NSTEMI
DES in unprotected LM lesions
DES in DM
DES in CTO
DES in In-stent restenosis
DES in saphenous vein graft
Saphenous Vein Grafts
PCI of saphenous vein grafts (SVGs) is
associated with worse outcomes and a high
incidence of in-stent restenosis.
The benefit of DES in this lesion subset has not
been formally evaluated because SVG lesions
have been excluded from randomized trials and
the available data come only from observational
studies.
Moreover, the higher local prothrombotic
conditions in SVG and the expected delay in
endothelial healing after DES are claimed as
possible drawbacks because both can lead to
higher rates of acute, subacute, and late
thrombosis.
Saphenous Vein Grafts
Both SES and PES have been evaluated in small
registries reporting low restenosis rates (10%)
without any increased risk of stent thrombosis
DES vs BMS
Background
What are DES?
Why DES?
Problems of DES
DES, special situations
What should we do now…?
To DES or not to DES?
Risks and Benefits of Drug Eluting Stents
Risk
Slight increase in LST >6m
Benefit
TLR reduced by >50%
Probable reduction in TLRrelated MI/death*
Indication for DES in 2007
according to the German Society of Cardiology
Indication
questionable
Indication
High Restenosis increased Risk of
Risk
Stent Trombosis
Small (< 2.5 mm) elderly patients
Long (> 15 mm) LV dysfunction
lesions
renal insufficiency
Restenosis in BMS diffuse disease
CTO recanalisation
ACS
Diabetes mell.
Contraindication
Non-Compliance
to Clopidogrel
planned non-cardiac Surgery
bleeding risk
Oral anticoagulat.
long overlapping
stents
Which DES should be recommended ?
STENT
DRUG
STUDY
High Level of Evidence, Efficacy proven in a randomized trial
with an adequate primary clinical endpoint:
Cypher
Sirolimus
SIRIUS
Taxus
Paclitaxel
TAXUS-IV, TAXUS-V,
(TAXUS-VI)
Endeavor
Zotarolimus
ENDEAVOR-II
Medium Level of Evidence, Efficacy proven in a randomized trial
with a primary surrogate endpoint:
Xience-V / Promus
Everolimus
SPIRIT-I, -II, -III
Yukon
Sirolimus
ISAR-Test
SO
Drug Eluting Stents Are Safe If Applied Appropriately
Use DES in
High risk for restenosis
Use BMS in
Very low restenosis risk (focal lesion large vessel)
Non-compliant patients
High bleeding risk
Patients requiring surgery
Consensus Panel Recommendations. Circ 2007;115&NA;-.
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Thank You