Transcript Drug Eluting Stents for In Stent Restenosis

Use of Drug Eluting Stents for
In-Stent Restenosis: Are We
There Yet?
Jose Diez, M.D.
Robert Smith, M.D.
Cardiac Catheterization Conference
March 23, 2004
Outline
• Case presentation with LHC results
• Traditional approaches for dealing with in-stent
restenosis
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Cutting Balloon Angioplasty (CBA)
Brachytherapy
PTCA
Bare Metal Stent
• Drug eluting stents for in-stent restenosis
• Conclusions
Case Presentation
JD is a 72 yo AAF with h/o CAD s/p stenting to RCA and LAD
in 10/03 who was referred for elective LHC after describing a
history of progressive SOB and chest pain. She described the
chest pain as precordial, pressure like, and similar to previous
episodes of angina. Her chest pain was typically less than a few
minutes, relieved with SL NTG, and occurred sometimes with
exertion and sometimes at rest. It was usually associated with
SOB. She first experienced the chest pain approximately 2
months after stent placement (12/03) and underwent a negative
stress echo at that time. In 2/04, she was evaluated and
discharged from the ER for similar episodes of chest pain with
SOB. Subsequently, an adenosine cardiolyte stress test was
negative for ischemia. Because of persistence of her symptoms,
she was referred for LHC.
Past Medical History
• CAD s/p STEMI in 10/03 with stent to culprit RCA lesion
(Medtronic Zipper) and stent to LAD (Cypher)
• Exercise stress echo 12/03 negative for ischemia. Pt
exercised for 7 minutes
• Adenosine cardiolyte stress test 2/04 negative for ischemia
• TTE 2000 showed moderate AI, concentric LVH, mild MR
• HTN for > 10 years
• Type II DM on oral hypoglycemics
• Hyperlipidemia
• PVD
• Cerebrovascular disease s/p left CEA and 60% lesion in
the right internal CA (h/o TIA’s)
• Obstructive Sleep Apnea on home CPAP
Medications
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Plavix 75mg PO QD
ASA 81mg PO QD
Lopressor 50mg PO BID
Lisinopril 40mg PO QD
Atorvastatin 80mg PO QHS
Social History
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Retired Nurse
Denies h/o cigarette smoking
Denies EtOH
Denies drug use
Lives with daughter
Husband is deceased
Family History
• Father died of “congestive heart failure”
• Also significant for DM, HTN
Physical Exam
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152/88 52 14 36.0 SaO2 97%
Gen: NAD, symptom free
Neck: Right Carotid Bruit, No JVD
CV: nlS1S2, 2/6 HSM apex  axilla
Chest: clear
Abd: NABS, NT, ND
Ext: no edema
Labs
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Na 133
K 4.1
Cl 101
CO2 29
Glu 172
BUN 11
Cr 0.6
Ca 1.8
Mg 1.8
Tn <0.04
Myo 22
CK 68
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WBC 6.6
Hgb 12.5
Hct 36.5
MCV 87.5
Plt 221
PTT 26
INR 1.02
ECG
• NSR with q waves in the inferior leads
Restenosis
• Occurs in 30-40% of patients by 6 months after
PTCA
• Occurs in 20-30% of patients by 6 months after
PTCA with stenting 1,2
• 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
1Fischman
et al., N Engl J Med 1994;331:496-501
2Serruys et al., N Engl J Med 1994;331:489-495
ISR; Available Therapies
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Cutting Balloon Angioplasty (CBA)
Angioplasty
Brachytherapy
Stent within Stent
– Bare Metal Stents
– Drug Eluting Stents
Cutting Balloon Angioplasty
• The cutting balloon is a device with 3-4
longitudinal atherotome blades mounted on the
outer surface of the device
• It produces longitudinal incisions in a target lesion
resulting in more effective dilatation of the lesion
• Keeps the balloon from moving proximally or
distally during inflation
• May help facilitate extrusion of in-stent
hyperplasia through the stent struts
Cutting Balloon
Cutting Balloon Angioplasty for ISR
• In a 2001 study, CBA was compared to rotational
atherectomy, PTCA, or restenting in a study of
684 patients with ISR1
• At angiographic f/u, CBA was associated with less
lumen loss than that seen with atherectomy and
stent
• This corresponded to a 6 month restenosis rate of
20% for CBA, 36% for atherectomy, and 41% for
restenting
• At 11 month follow up, there was no difference in
the incidence death, MI, or bypass surgery
1Adamian
et al. J Am Coll Cardiol 2001 Sep;38(3):672-9
Brachytherapy for ISR
• Intracoronary brachytherapy reduces vessel wall
remodeling and causes a reduction in the
proliferation of the neointima
• The SCRIPPS Trial1 was a double blind
randomized trial that compared gamma irradiation
to placebo for treatment of ISR (n=55). Follow
up was performed at 6 months, 3 years, and 5
years
• 23% of patients had recurrent stenosis at
angiographic follow up
1Grise
et al., Circulation. 105(23):2737-2740, June 11, 2002
SCRIPPS Trial: 5 Year F/U
SCRIPPS Trial: TLR
SCRIPPS Trial: Event Free Survival
PTCA for ISR
• In a 1998 study, PTCA was performed in 52
patients presenting with ISR 1
• Initial angiographic success rate was 100%
• At 6 month follow up, angiographic restenosis rate
was 54%
• 18 patients (35%) had TVR
• No patients died
• Conclusions: PTCA for ISR is safe but has a high
rate of recurrent stenosis
1Eltchaninoff
et al., J Am Coll Cardiol 1998 Oct;32(4): 980-984
Repeat Stenting for ISR
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In a study from 2000, 65 patients underwent
repeat stenting as treatment for ISR 1
Angiographic success was obtained in all
patients
3 patients had acute adverse events (1 death, 2
NQWMI’s)
During follow up (17+/- 11 months), TVR was
required in 14%
Angiographic follow up (mean of 9 months)
showed ISR in 30%
Alfonso et al., Am J Cardiol 2000 Feb 1;85(3):327-32
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Repeat Stenting vs. PTCA
• Addressed in the RIBS trial1 (compared repeat
stenting to PTCA alone in 450 patients)
• Restenosis rate and event free survival at 6
months were similar in the two groups
• Among patients with a target vessel diameter > or
equal to 3mm, stenting was associated with a
significantly lower restenosis rate (27% vs. 49%
for PTCA) at 6 months
Alfonso et al., J Am Coll Cardiol 2003 Sep 3;42(5):796-805
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Repeat Stenting vs. PTCA
• In vessels > or equal to 3mm, patients who
were restented had better event free one
year survival (84% vs. 62%)
• There was an almost significant trend
toward worse outcomes with re-stenting
when the vessel diameter was less than
3mm
Summary of Restenosis Rates
• Brachytherapy: 12% at 6 months and 23%
at 5 years
• CBA: 20% at 6 months
• PTCA: 54% at 6 months, 49% at 6 months
• Bare Metal Stents: 41% at 6 months, 30% at
9 months, 27% at 6 months
Drug Eluting Stents for ISR
• The efficacy of Sirolimus Eluting Stents has been
evaluated in 2 small, noncomparative trials 1,2
• The efficacy of Paclitaxel eluting stents has also
been evaluated in a single noncomparative trial 3
1Degertekin
et al., J Am Coll Cardiol 2003 Jan 15;41(2):184-9
2Sousa et al., Circulation 2003; 107:24
3Tanabe et al., Circulation 2003 Feb 4;107(4): 559-564
Drug Eluting Stents for ISR
• In an initial series of 25 patients with ISR in
whom a SES was implanted, all vessels were
patent at 1 year and only one patient developed
ISR within the newer stent 1
• Exclusion criteria for this study included lesions in
SVG’s, patients who had undergone previous
brachytherapy to the target vessel, and lesions
greater than 36mm in length
• No ostial lesions were treated in this study
Sousa et al., Circulation 2003; 107:24
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Drug Eluting Stents for ISR
• Post procedure angiography and IVUS was
performed at 4 and 12 months
• All patients were free of angina after 1 year
• There were no repeat revascularizations, stent
thromboses, or major clinical events (CVA, MI,
Death) after 1 year
• On 4 month angiographic follow up, lumen
diameter was unchanged in 50% of patients, and
slightly greater in some patients
Drug Eluting Stents for ISR
• There was a slight but significant decrease in
mean lumen diameter between 4 and 12 months
(angiographic late loss averaged 0.07mm at 4
months and 0.36mm at 12 months)
• Volume obstruction by IVUS was 0.81% at 4
months and 1.76% at 12 months
• No patients had ISR at 4 months and 1 patient had
ISR at 1 year
• All stents were properly deployed
Drug Eluting Stents for ISR
• In a second report1, 16 patients with severe,
recurrent ISR in a native coronary vessel received
a SES (average lesion length 18.4mm)
• Patients with objective evidence of ischemia were
excluded
• 4 patients has total occlusions pre-procedure and
3 others had received brachytherapy
• Quantitative angiographic and IVUS follow up
was performed at 4 months and clinical follow up
at 9 months
1Degertekin
et al., J Am Coll Cardiol 2003 Jan 15;41(2):184-9
Drug Eluting Stents for ISR
• At 4 month follow up, one patient had died and
three patients had angiographic evidence of
restenosis (18.8%)
• Late lumen loss averaged 0.21mm and volume
obstruction of the stent by IVUS was 1.1%
• At 9 months clinical follow up, 3 patients had
experienced major adverse events (2 deaths and 1
MI)
Drug Eluting Stents for ISR
• The TAXUS III Trial1 evaluated paclitaxel eluting
stents for treatment of ISR
• This was a noncomparative 2 center study that
evaluated 28 patients with ISR
• Inclusion criteria were lesions < or = to 30mm,
50-99% stenosis, and vessel diameter 3.0 to
3.5mm
• Exclusion criteria were AMI, LVEF <30%, CVA
within 6 months, SCr >1.7, and contraindication to
antiplatelet therapy
1Tanabe
et al., Circulation 2003 Feb 4;107(4): 559-564
Drug Eluting Stents for ISR
• There was no subacute stent thrombosis
• 25 of 28 patients completed angiographic follow up at 6
months
• 4 patients had angiographic evidence of restenosis (16%)
• One of these patients had total occlusion of a lesion
previously treated with a gold coated stent (he was
asymptomatic)
• One patient had ISR in a bare metal stent used to treat a
dissection at the end of a PES
• Two patients has ISR in gaps between sequential PES’s
• The mean lumen late loss was 0.54mm
Drug Eluting Stents for ISR
• The major adverse cardiac event rate was 29% (8
patients)
• This included 1 NQWMI, 1 CABG, and 5 TLR’s
• 1 patient with ISR of bare metal stent and 2
patients with stenoses of gaps between PES’s
• 2 patients without angiographic restenosis
underwent TLR as result of IVUS assessment at
follow up (1 incomplete apposition and 1
insufficient expansion of the stent
Conclusions
• Treating ISR is a major challenge facing
interventional cardiologists
• With traditional treatments (PTCA, CBA, restenting), restenosis develops in 30-80% of
patients
• Prior to drug eluting stents, the best therapy was
intravascular brachytherapy (23% restenosis in the
SCRIPPS trial)
• Early studies indicate that drug eluting stents may
prove effective for treating in-stent restenosis
Conclusions
• Between all DES studies, there was no subacute
thrombosis
• Between all studies, there were only 4 compelling cases of
ISR within a DES
• When the DES’s were properly deployed, there were only
6 adverse cardiac events between the studies
• Sirolimus eluting stents and paclitaxel eluting stents both
appear to be effective for treating ISR
• Early data indicates that DES’s are superior than traditional
methods for treating ISR
• Are we there yet? Maybe…