Download Two-Year Outcomes After Sirolimus-Eluting Stent Implantation

Journal of the American College of Cardiology
© 2006 by the American College of Cardiology Foundation
Published by Elsevier Inc.
Vol. 47, No. 7, 2006
ISSN 0735-1097/06/$32.00
doi:10.1016/j.jacc.2005.11.077
CLINICAL RESEARCH
Interventional Cardiology
Two-Year Outcomes After
Sirolimus-Eluting Stent Implantation
Results From the Sirolimus-Eluting Stent
in de Novo Native Coronary Lesions (SIRIUS) Trial
Giora Weisz, MD,* Martin B. Leon, MD,* David R. Holmes, JR, MD,† Dean J. Kereiakes, MD,‡
Mel R. Clark, MD,§ Barry M. Cohen, MD,¶ Stephen G. Ellis, MD,储 Patrick Coleman, MD,#
Carolyn Hill,** Chunxue Shi, MS,†† Donald E. Cutlip, MD,‡‡ Richard E. Kuntz, MD, MSC,§§
Jeffrey W. Moses, MD*
New York, New York; Rochester, Minnesota; Cincinnati and Cleveland, Ohio; Oklahoma City, Oklahoma;
Morristown and Warren, New Jersey; Santa Rosa, California; and Boston, Massachusetts
The purpose of this study was to examine the two-year clinical outcomes in patients enrolled
in the Sirolimus-Eluting Stent in De Novo Native Coronary Lesions (SIRIUS) study.
BACKGROUND The SIRIUS study was a double-blinded randomized study which demonstrated that
sirolimus-eluting stents (SES) significantly improved angiographic results (at 8 months) and
clinical outcomes (at 9 and 12 months) compared with bare-metal stents (BMS).
METHODS
Patients with de novo native coronary artery lesions randomized to either SES (533 patients)
or control BMS (525 patients) were followed for two years.
RESULTS
Between one and two years, there were infrequent additional clinical events that were equally
distributed between the sirolimus and control groups. After two years, target lesion
revascularization was 5.8% and 21.3% in SES and control patients, respectively (p ⬍ 0.001),
and major adverse cardiovascular events and target vessel failure rates were 10.1% versus
24.4% and 12.0% versus 26.7%, respectively (p ⬍ 0.0001 for both). There were no differences
in death, myocardial infarction, and stent thrombosis between the two groups.
CONCLUSIONS Clinical outcomes two years after implantation of SES continue to demonstrate significant
reduction in the need for repeat target lesion (and vessel) revascularization compared with
BMS without evidence for either disproportionate late restenosis or late stent
thrombosis. (J Am Coll Cardiol 2006;47:1350 –5) © 2006 by the American College of
Cardiology Foundation
OBJECTIVES
In multiple blinded randomized clinical trials, drug-eluting
stents (containing sirolimus or paclitaxel) have shown significant improvement in angiographic and clinical outcomes
compared with bare-metal stents (BMS) (1–9). However,
there are sparse data supporting the long-term benefits of
See page 1361
drug-eluting stents in patients with coronary lesions beyond
the first year after stent implantation (10,11). The
From the *Cardiovascular Research Foundation and Columbia University Medical
Center, New York, New York; †Saint Mary’s Hospital, Rochester, Minnesota; ‡Ohio
Heart Health Center, Cincinnati, Ohio; §Intergris Oklahoma Heart Center, Oklahoma City, Oklahoma; ¶Morristown Memorial Hospital, Morristown, New Jersey;
储Cleveland Clinic Foundation, Cleveland, Ohio; #Northern California Research
Association, Santa Rosa, California; **Cordis (Johnson & Johnson), Warren, New
Jersey; ††Harvard Clinical Research Institute, Boston, Massachusetts; ‡‡Beth Israel
Deaconess Medical Center, Boston, Massachusetts; and §§Brigham and Women’s
Hospital, Boston, Massachusetts. Dr. Leon is supported by a Cordis research grant
and holds stock in Johnson & Johnson. Dr. Cohen is a member of the Cordis speakers
bureau and holds stock in Johnson & Johnson. Dr. Ellis has received a consulting fee
from Cordis. Dr. Moses has received a consulting fee from Cordis and holds stock in
Johnson & Johnson.
Manuscript received January 9, 2005; revised manuscript received October 28,
2005, accepted November 7, 2005.
Sirolimus-Eluting Stent in De Novo Native Coronary
Lesions (SIRIUS) multicenter blinded randomized trial
examined the safety and efficacy of sirolimus-eluting stents
(SES) in 1,058 patients, and results up to one year indicated
significant reduction in both restenosis and target lesion
revascularization (TLR) (2,3). This report extends the
clinical follow-up of the original SIRIUS patient cohort to
determine if the early and middle-term safety and efficacy of
SES is maintained at two years.
METHODS
Study design and eligibility criteria. The methods of the
SIRIUS trial were previously reported (2). Patients enrolled
in the study had a clinical history of angina and single
coronary target lesions, 15 to 30 mm in length, in vessels 2.5
to 3.5 mm in diameter. Major exclusion criteria included
recent myocardial infarction, left ventricular ejection fraction ⬍25%, target lesion in an ostial or bifurcation location,
or a thrombotic or severely calcified lesion.
Data collection and follow-up. Patients had clinical evaluations at 30 days and 6, 9, 12, and 24 months. Two-year
clinical follow-up was supervised by the physician investigators and the study coordinators from each of the enrolling
Weisz et al.
The SIRIUS Trial: Two-Year Follow-Up
JACC Vol. 47, No. 7, 2006
April 4, 2006:1350–5
Abbreviations and Acronyms
BMS
⫽ bare-metal stents
LAD
⫽ left anterior descending coronary artery
MACE ⫽ major adverse cardiac event
PES
⫽ paclitaxel-eluting stents
SES
⫽ sirolimus-eluting stents
SIRIUS ⫽ Sirolimus-Eluting Stent in De Novo Native
Coronary Lesions
TLR
⫽ target lesion revascularization
TVF
⫽ target vessel failure
TVR
⫽ target vessel revascularization
sites. Patients were queried by telephone interview, and in
the case of clinical events, source medical documents were
retrieved and reviewed and adjudicated by an independent
Clinical Events Committee blinded to the treatment assignment. Complete data compliance for all two-year follow-up
end points was 91.6% for the BMS group and 92.3% for the
SES group.
Study end points. This two-year follow-up study focuses
on clinical restenosis or TLR, defined as the need for
clinically driven repeat percutaneous intervention of the
target lesion or bypass surgery of the target vessel. Clinical
indications for repeat revascularizations included a positive
noninvasive functional study, ischemic electrocardiogram
changes at rest in a distribution consistent with the target
vessel, or ischemic symptoms and an in-lesion diameter
stenosis by quantitative coronary angiography of ⱖ50%. In
addition, in the absence of the aforementioned objective
criteria for ischemia, an in-lesion diameter stenosis by
quantitative coronary angiography of ⱖ70% was also considered of sufficient severity to justify repeat revascularization. The independent Clinical Events Committee blindly
adjudicated all clinically driven revascularization episodes.
The SIRIUS secondary clinical end points included nonTLR target vessel revascularization (TVR), target vessel
failure (TVF), and major adverse cardiac events (MACE).
The definitions of these end points have been previously
described (2).
Early stent thrombosis, either acute (within 24 h) or
subacute (between 24 h and 30 days), was defined as
angiographic documentation of target vessel occlusion or
any death or myocardial infarction occurring within 30 days
that is not clearly related to causes other than stent occlusion. The protocol definition of late stent thrombosis was
myocardial infarction occurring ⬎30 days after the index
procedure and attributable to the target vessel, angiographic
documentation (site-reported or by quantitative coronary
angiography) of thrombus or total occlusion of the target
site, and freedom from an interim revascularization of the
target vessel. This very stringent definition represents definite late stent thrombosis. For the purposes of this report,
we have extended the definition of late stent thrombosis to
include additional categories of possible and cannot exclude
late stent thrombosis. The definition of possible late stent
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thrombosis includes patients with myocardial infarction
occurring ⬎30 days after the index procedure and attributable to the target vessel, no identifiable “culprit” lesion
elsewhere, and freedom from an interim revascularization of
the target vessel. The definition of cannot exclude late stent
thrombosis includes patients with sudden cardiac death ⬎30
days after the index procedure, no identifiable “culprit”
lesion elsewhere (as suggested by nontarget vessel electrocardiogram changes or autopsy evidence of a patent target
vessel), and freedom from interim TVR.
Statistical analysis. The effectiveness analysis and the
safety evaluation were performed on a modified intent-totreat population; de-registered patients were not included in
the analysis because they received neither study treatment.
Continuous variables are summarized as means and
standard deviations and compared between treatment
groups using t test. Categorical variables are summarized as
frequencies and percentages and compared between treatment groups using the Fisher exact test. Out-of-hospital
outcomes are summarized as Kaplan-Meier event rates and
compared between treatment groups using log-rank tests.
All tests are two-sided with a significance level of 0.05.
Multivariate predictors were identified by using a Cox
model with an entry/stay criteria of 0.10/0.15. All statistical
analyses were performed with SAS software (version 6.12;
SAS Institute, Cary, North Carolina).
RESULTS
As previously reported, both groups had similar baseline
clinical and angiographic characteristics, procedural factors,
and acute (in-hospital) results (2).
Long-term clinical outcomes. At two years, the significant differences between the SES and BMS groups in TLR,
TVR, TVF, and MACE were all maintained (Table 1, Fig.
1). There were small increases in both groups and still no
differences in death or myocardial infarction. The specific
etiologies of all-cause mortality between one and two years,
included cardiac deaths in two patients (chest pain followed
by cardiac arrest, one case in each group) and noncardiac
deaths in five patients (one case of documented noncardiac
sudden death in the SES group, two deaths due to severe
chronic lung disease in the SES group, and two deaths due
to malignancy in the control group). There were infrequent
late TLR events in both groups between one and two years
(0.9% for SES and 1.3% for control stents), and the
magnitude of reduction in clinical restenosis was the same at
one and two years (TLR 5.8% for SES group and 21.3% for
controls at two years; p ⬍ 0.001).
Various higher restenosis-risk patient and lesion subgroups (including diabetes, left anterior descending coronary artery [LAD] lesion location, small vessel size, and
long lesion length) were examined by univariate analysis
(Fig. 2). In all cases, the significant reduction in TLR
associated with SES compared with BMS controls in these
selected subgroups was maintained at two years. Factors that
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The SIRIUS Trial: Two-Year Follow-Up
JACC Vol. 47, No. 7, 2006
April 4, 2006:1350–5
Table 1. Cumulative Clinical Events at One and Two Years’
Clinical Follow-Up
All events at 1 year
Death
Cardiac
Non-cardiac
MI (all)
Q-wave
Non–Q-wave
TLR (clinically driven)
TL CABG
TL PCI
TVR (non-TLR)
MACE
TVF
All events at 2 years
Death
Cardiac
Non-cardiac
MI (all)
Q-wave
Non-Q-wave
TLR (clinically driven)
TL CABG
TL PCI
TVR (non-TLR)
MACE
TVF
All events between 1 and 2 years
Death
Cardiac
Non-cardiac
MI (all)
Q-wave
Non-Q-wave
TLR (clinically driven)
TL CABG
TL PCI
TVR (non-TLR)
MACE
TVF
SES
(n ⴝ 533)
CS
(n ⴝ 525)
p Value
7 (1.3)
3 (0.5)
4 (0.8)
16 (3.0)
4 (0.8)
12 (2.3)
26 (4.9)
5 (0.9)
23 (4.3)
19 (3.6)
44 (8.3)
52 (9.8)
4 (0.8)
2 (0.4)
2 (0.4)
18 (3.4)
2 (0.4)
16 (3.0)
105 (20.0)
9 (1.7)
101 (19.2)
35 (6.7)
117 (22.3)
24.8 (130)
0.547
1.000
0.678
0.730
0.687
0.449
⬍0.0001
0.295
⬍0.0001
0.025
⬍0.001
⬍0.0001
11 (2.1)
4 (0.8)
7 (1.3)
22 (4.1)
6 (1.1)
17 (3.2)
31 (5.8)
6 (1.1)
28 (5.3)
26 (4.9)
55 (10.3)
64 (12.0)
7 (1.3)
3 (0.6)
4 (0.8)
25 (4.8)
5 (1.0)
20 (3.8)
112 (21.3)
13 (2.5)
108 (20.6)
38 (7.2)
132 (25.1)
140 (26.7)
0.477
1.000
0.547
0.656
1.000
0.618
⬍0.0001
0.110
⬍0.0001
0.122
⬍0.0001
⬍0.0001
4 (0.8)
1 (0.2)
3 (0.6)
6 (1.1)
2 (0.4)
5 (0.9)
5 (0.9)
1 (0.2)
5 (0.9)
7 (1.3)
11 (2.0)
12 (2.3)
3 (0.6)
1 (0.2)
2 (0.4)
7 (1.3)
3 (0.6)
4 (0.8)
7 (1.3)
4 (0.8)
7 (1.3)
3 (0.6)
15 (2.9)
10 (1.9)
1.000
1.000
1.000
1.000
1.000
1.000
0.576
0.214
0.576
0.342
0.433
0.830
Values are % (no. of cases). Events at 1 year were reported previously (15).
CS ⫽ control stent; MI ⫽ myocardial infarction; PCI ⫽ percutaneous coronary
intervention; SES ⫽ sirolimus-eluting stent; TL ⫽ target lesion; TLR ⫽ target lesion
revascularization; TVF ⫽ target vessel failure; TVR ⫽ target vessel revascularization.
predicted TLR at two years were evaluated using multiple
logistic regression analysis in the entire study group and in
the SES group alone. In the entire study group, independent predictors of TLR included assignment to sirolimus
treatment (hazard ratio [HR] 0.21; p ⬍ 0.001), reference
vessel diameter (HR 0.55; p ⬍ 0.02), diabetes mellitus (HR
1.56; p ⫽ 0.03), LAD location (HR 1.06; p ⫽ 0.03), and
total stent length (relative 3% increase in risk for each 1-mm
increase in stent length; p ⬍ 0.0001).
Stent thrombosis episodes (definite, possible, and cannot
exclude) were distributed into early events (up to 30 days
after the index procedure), late events up to 1 year, and late
events between 1 and 2 years for both the SES and the
control patients (Table 2). Early stent thrombosis and
definite late stent thrombosis up to one year was observed in
two SES patients (0.4%) and in four control patients (0.8%).
Definite late stent thrombosis between one and two years
was seen in one additional SES patient and in no control
patients (overall definite stent thrombosis frequency up to
two years was 0.6% for SES and 0.8% for control; nonsignificant difference). Possible late stent thrombosis occurred
in no SES patients and in two control patients (one between
30 days and 1 year and one between 1 and 2 years). Cannot
exclude late stent thrombosis occurred in two SES patient
(one between 30 days and 1 year and one between 1 and 2
years) and in two control patients (one between 30 days and
1 year and one between 1 and 2 years). Overall cumulative
stent thrombosis (including all categories of late stent
thrombosis) up to two years after the index procedure
occurred in five SES (0.9%) and in eight control BMS
patients (1.5%, p ⫽ 0.11).
DISCUSSION
Over the past two years, since the introduction of drugeluting stents into the U.S., there has been an evolving
change in the treatment paradigm such that the vast
majority of current patients receive SES or paclitaxeleluting stents (PES) during percutaneous coronary interventions. Studies examining angiographic, intravascular ultrasound, and clinical end points have demonstrated safety and
efficacy of these devices during the first year after therapy
(1–9,12,13). Long-term follow-up after drug-eluting stent
implantation is only available for small numbers of patients
with focal uncomplicated lesion morphologies (10,11).
Therefore, rigorous late clinical follow-up of the earliest
patient cohorts from large randomized clinical trials exposed
to drug-eluting stents becomes essential to ensure patient
safety and to determine if antirestenosis efficacy is maintained. The major findings of this two-year follow-up report
involving patients treated with SES from the SIRIUS trial
are: 1) clinical restenosis (with blinded adjudication of all
clinically driven TLR events) shows maintained antirestenosis efficacy; and 2) late complications such as stent
thrombosis between one and two years were rare and
occurred with similar frequency in SES and BMS groups.
The concern of late restenosis (after 6 to 12 months) with
potent antiproliferative therapies derives from experiences
with intravascular radiation (vascular brachytherapy) which
was introduced for the prevention of recurrent in-stent restenosis. Despite the significant short-term efficacy of vascular
brachytherapy systems (14 –18), long-term follow-up results
have been less gratifying. A small series of patients with
serial angiography and intravascular ultrasound demonstrated relatively early “catch-up” or delayed restenosis
(manifested as increased late-loss lumen loss) between 6 and
12 months after beta-vascular brachytherapy (19). More
importantly, the five-year follow-up of the gamma-vascular
brachytherapy Washington Radiation for In-Stent Restenosis Trial (WRIST) (in-stent restenosis patients) showed
that between 6 and 60 months, patients treated with
JACC Vol. 47, No. 7, 2006
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Weisz et al.
The SIRIUS Trial: Two-Year Follow-Up
1353
Figure 1. Kaplan-Meier event-free survival at two years for target lesion revascularization (TLR), major adverse coronary events (MACE), and target vessel
failure (TVF). p ⬍ 0.001 for all comparisons of sirolimus-eluting stent (SES) vs. control bare-metal stent.
intravascular radiation compared with placebo had four
times greater late TLR (21.6% vs. 4.7%; p ⫽ 0.04) (20).
This late “catch-up” or delayed restenosis phenomena has
also been observed with some of the earlier drug-eluting
stents. In a small study involving in-stent restenosis patients, the QuaDS-QP2 stent (polymer sleeve eluting a
taxane derivative, Quanam Medical Corp., Santa Clara,
California) resulted in excellent reduction in restenosis at 6
months, but marked deterioration in angiographic and
clinical outcomes after 12-month evaluations (21). The
current analysis from the SIRIUS trial, the largest random-
ized study (1,058 patients) treating patients with SES (2), is
particularly meaningful because there was no evidence of
disproportionate late clinical events with SES, including
death, myocardial infarctions, stent thrombosis, and repeat
revascularizations after two-year follow-up (Table 1, Fig. 1).
A recent report (22) has raised concerns that PES and
SES may be associated with an increased frequency of late
stent thrombosis episodes, in the setting of cessation of
antiplatelet therapy. A total of four patients (two with SES
and two with PES) experienced late stent thrombosis (at
least six months after the index procedure), within days after
Figure 2. Odds ratios for target lesion revascularization at 720 days for the overall population and by subgroup. Values represent event rates (%) in each
arm by subgroup. Bars represent odds ratio point estimates and 95% confidence intervals (CI). LAD ⫽ treatment of lesions in the left anterior descending
artery.
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Table 2. Stent Thrombosis (Up to Two Years’ Follow-Up)
Early
Late
0–30 days
Definite
Possible
Cannot exclude
All events
31–360 days
Overall
361–720 days
0–720 days
SES
CS
SES
CS
SES
CS
SES
CS
p Value
1 (0.2%)
0
0
1 (0.2%)
1 (0.2%)
0
0
1 (0.2%)
1 (0.2%)
0
1 (0.2%)
2 (0.4%)
3 (0.6%)
1 (0.2%)
1 (0.2%)
5 (1.0%)
1 (0.2%)
0
1 (0.2%)
2 (0.4%)
0
1 (0.2%)
1 (0.2%)
2 (0.6%)
3 (0.6%)
0
2 (0.4%)
5 (0.9%)
4 (0.8%)
2 (0.4%)
2 (0.4%)
8 (1.5%)
0.7237
0.2460
0.2144
0.1136
See Methods section for the various categories of stent thrombosis (definite, possible, and cannot exclude).
Abbreviations as in Table 1.
the cessation of all antiplatelet therapy (both aspirin and
clopidogrel). In three of these four patients, the thrombotic
episodes were during or after surgical or endoscopic procedures, and in two of the patients stent thrombosis was only
in the drug-eluting stent target vessel, whereas BMS in
other vessels were confirmed to be patent. Based on these
concerns, the SIRIUS patients were analyzed in far greater
detail employing an expanded definition of late stent thrombosis to include those patients without angiographic documentation of stent thrombus or occlusion and even in those
patients with unexplained sudden cardiac death (Table 2).
Of note, dual antiplatelet therapy using aspirin and clopidogrel was maintained for only three months in SIRIUS
patients, whereupon the aspirin was routinely continued and
the clopidogrel was stopped. Overall, we could not determine any differences in definite, possible, and cannot exclude
late stent thrombosis (up to two years) when comparing the
SES and BMS treated patients. Cumulative overall stent
thrombosis using the less rigorous definitions was 0.9% in
SES patients and 1.5% in control patients (p ⫽ 0.11).
Interestingly, there were two episodes of possible late stent
thrombosis that occurred in the BMS group, one soon after
cessation of aspirin therapy in a woman anticipating a
scheduled elective hysterectomy (clopidogrel had already
been stopped months previously) and another during noncardiac surgery after both aspirin and clopidogrel had been
stopped. Thus, although we recognize that late stent thrombosis will continue to be a carefully scrutinized clinical complication after drug-eluting stent implantation, especially in an
environment where more complex lesion subsets are being
treated, we cannot ascertain in the SIRIUS trial any differences
in overall and late stent thrombosis between SES and BMS.
Conclusions. The maintained clinical safety and improved
efficacy at two years in SIRIUS patients should provide
some confidence that late untoward events are unlikely to be
associated with SES. Nevertheless, the SIRIUS trial only
included patients with intermediate lesion complexity, and
the results cannot be extrapolated to all patient subsets and
lesion subgroups. Therefore, additional clinical data are
required in more complex patients and lesions to make
categorical statements about long-term safety and efficacy of
SES. Importantly, annual follow-up of the SIRIUS patients
will continue for five years to provide further assurance that this
frequently utilized and important interventional device fulfills
the most rigorous standards of long-term safety and efficacy.
Reprint requests and correspondence: Dr. Martin B. Leon,
Center for Interventional Vascular Therapy, Columbia University
Medical Center, Herbert Irving Pavilion, 161 Fort Washington
Avenue, 5th Floor, New York, New York 10032. E-mail:
[email protected].
REFERENCES
1. Morice MC, Serruys PW, Sousa JE, et al. A randomized comparison
of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002;346:1773– 80.
2. Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus
standard stents in patients with stenosis in a native coronary artery.
N Engl J Med 2003;349:1315–23.
3. Holmes DR Jr., Leon MB, Moses JW, et al. Analysis of 1-year clinical
outcomes in the SIRIUS trial: a randomized trial of a sirolimus-eluting
stent versus a standard stent in patients at high risk for coronary
restenosis. Circulation 2004;109:634 – 40.
4. Schofer J, Schluter M, Gershlick AH, et al. Sirolimus-eluting stents
for treatment of patients with long atherosclerotic lesions in small
coronary arteries: double-blind, randomised controlled trial (ESIRIUS). Lancet 2003;362:1093–9.
5. Schampaert E, Cohen EA, Schluter M, et al. The Canadian study of
the sirolimus-eluting stent in the treatment of patients with long de
novo lesions in small native coronary arteries (C-SIRIUS). J Am Coll
Cardiol 2004;43:1110 –5.
6. Grube E, Silber S, Hauptmann KE, et al. TAXUS I: six- and
twelve-month results from a randomized, double-blind trial on a
slow-release paclitaxel-eluting stent for de novo coronary lesions.
Circulation 2003;107:38 – 42.
7. Colombo A, Drzewiecki J, Banning A, et al. Randomized study to
assess the effectiveness of slow- and moderate-release polymer-based
paclitaxel-eluting stents for coronary artery lesions. Circulation 2003;
108:788 –94.
8. Stone GW, Ellis SG, Cox DA, et al. A polymer-based, paclitaxeleluting stent in patients with coronary artery disease. N Engl J Med
2004;350:221–31.
9. Stone GW, Ellis SG, Cox DA, et al. One-year clinical results with the
slow-release, polymer-based, paclitaxel-eluting TAXUS stent: the
TAXUS-IV trial. Circulation 2004;109:1942–7.
10. Sousa JE, Costa MA, Sousa AG, et al. Two-year angiographic and
intravascular ultrasound follow-up after implantation of sirolimuseluting stents in human coronary arteries. Circulation 2003;107:381–3.
11. Fajadet J, Morice MC, Bode C, et al. Maintenance of long-term
clinical benefit with sirolimus-eluting coronary stents: three-year
results of the RAVEL trial. Circulation 2005;111:1040 – 4.
12. Sousa JE, Costa MA, Abizaid A, et al. Lack of neointimal proliferation after implantation of sirolimus-coated stents in human coronary
arteries: a quantitative coronary angiography and three-dimensional
intravascular ultrasound study. Circulation 2001;103:192–5.
13. Sousa JE, Costa MA, Abizaid AC, et al. Sustained suppression of
neointimal proliferation by sirolimus-eluting stents: one-year angiographic and intravascular ultrasound follow-up. Circulation 2001;104:
2007–11.
JACC Vol. 47, No. 7, 2006
April 4, 2006:1350–5
14. Teirstein PS, Massullo V, Jani S, et al. Catheter-based radiotherapy to inhibit
restenosis after coronary stenting. N Engl J Med 1997;336:1697–703.
15. Waksman R, White RL, Chan RC, et al. Intracoronary gammaradiation therapy after angioplasty inhibits recurrence in patients with
in-stent restenosis. Circulation 2000;101:2165–71.
16. Leon MB, Teirstein PS, Moses JW, et al. Localized intracoronary
gamma-radiation therapy to inhibit the recurrence of restenosis after
stenting. N Engl J Med 2001;344:250 – 6.
17. Popma JJ, Suntharalingam M, Lansky AJ, et al. Randomized trial of
90Sr/90Y beta-radiation versus placebo control for treatment of
in-stent restenosis. Circulation 2002;106:1090 – 6.
18. Waksman R, Raizner AE, Yeung AC, Lansky AJ, Vandertie L. Use of
localised intracoronary beta radiation in treatment of in-stent restenosis:
the INHIBIT randomised controlled trial. Lancet 2002;359:551–7.
Weisz et al.
The SIRIUS Trial: Two-Year Follow-Up
1355
19. Munoz JS, Feres F, Abizaid A, et al. Long-term efficacy of intracoronary beta-radiation for the treatment of in-stent restenosis: an angiographic and intravascular ultrasound analysis of the late catch-up
phenomenon. J Am Coll Cardiol 2004;43:69A.
20. Waksman R, Ajani AE, White RL, et al. Five-year follow-up after
intracoronary gamma radiation therapy for in-stent restenosis. Circulation 2004;109:340 – 4.
21. Liistro F, Stankovic G, Di Mario C, et al. First clinical experience with
a paclitaxel derivate-eluting polymer stent system implantation for
in-stent restenosis: immediate and long-term clinical and angiographic
outcome. Circulation 2002;105:1883– 6.
22. McFadden EP, Stabile E, Regar E, et al. Late thrombosis in
drug-eluting stents after discontinuation of antiplatelet therapy. Lancet 2004;364:1519 –21.