(Circulation. 2000;102:951.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Inhibition of Restenosis With ß-Emitting Radiotherapy
Report of the Proliferation Reduction With Vascular Energy Trial (PREVENT)
u
a, MD, PhDFrom Baylor College of Medicine, Houston, Tex (A.E.R., J.K.C., G.L.K., N.M.A.); Stanford University, Stanford, Calif (S.N.O., A.C.Y., P.J.F.); Washington Hospital Center, Washington, DC (R.W., L.R.W.); Thoraxcenter, Rotterdam, The Netherlands (P.W.S., W.J.v.d.G.); Centro Cuore Columbus, Milan, Italy (A.C.); National Heart Center, Singapore (Y.-L.L.); and Guidant Vascular Intervention, Santa Clara, Calif (L.V.).
Correspondence to Albert E. Raizner, MD, Director, Cardiac Catheterization Laboratories, The Methodist Hospital, 6535 Fannin, FB 1034, Houston, TX 77030. E-mail araizner{at}tmh.tmc.edu
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Abstract |
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 Top Abstract IntroductionMethodsResultsDiscussionReferences |
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Background—Intracoronary
- and ß-radiation have reduced restenosis in animal
models. In the clinical setting, the effectiveness of ß-emitters has
not been studied in a broad spectrum of patients, particularly those
receiving stents.
Methods and Results—A prospective, randomized, sham-controlled
study of intracoronary radiotherapy with the ß-emitting
32P source wire, using a centering catheter and automated
source delivery unit, was conducted. A total of 105 patients with de
novo (70%) or restenotic (30%) lesions who were treated by
stenting (61%) or balloon angioplasty (39%) received 0 (control), 16,
20, or 24 Gy to a depth of 1 mm in the artery wall. Angiography at
6 months showed a target site late loss index of 11±36% in
radiotherapy patients versus 55±30% in controls
(P<0.0001). A low late loss index was seen in stented
and balloon-treated patients and was similar across the 16, 20, and 24
Gy radiotherapy groups. Restenosis (
50%) rates were
significantly lower in radiotherapy patients at the target site (8%
versus 39%; P=0.012) and at target site plus adjacent
segments (22% versus 50%; P=0.018). Target lesion
revascularization was needed in 5 radiotherapy
patients (6%) and 6 controls (24%; P<0.05).
Stenosis adjacent to the target site and late thrombotic events
reduced the overall clinical benefit of radiotherapy.
Conclusions—ß-radiotherapy with a centered 32P source is safe and highly effective in inhibiting restenosis at the target site after stent or balloon angioplasty. However, minimizing edge narrowing and late thrombotic events must be accomplished to maximize the clinical benefit of this modality.
Key Words: radiotherapy • radiation • restenosis • radioisotopes • stents • coronary disease
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Radiation therapy with
- and ß-emitting sources
inhibits restenosis after percutaneous
coronary interventions.1 Human trials with
endovascular -radiation demonstrated reduced restenosis in
patients with prior restenosis undergoing repeat
coronary angioplasty followed by radiotherapy.2 3
Nonrandomized pilot studies using endovascular ß-radiation after
balloon angioplasty showed a low late lumen loss and a low
restenosis rate in patients with de novo lesions4
and those with in-stent restenosis.5 The Proliferation Reduction with Vascular Energy Trial (PREVENT) is a randomized trial of intracoronary radiation with 32P, a ß-emitting source, in patients with restenotic and de novo lesions in whom preradiation treatment with stents or balloon angioplasty was allowed. As such, it represents a trial of ß-emitting radiotherapy in a broad spectrum of patients undergoing percutaneous coronary interventions. The primary objective of this study was to demonstrate the safety and performance of intracoronary radiation therapy using an automated source-delivery unit and a source-centering mechanism (Guidant Vascular Intervention). Secondary objectives included evaluating the effectiveness of intravascular radiotherapy after stent implantation compared with balloon angioplasty alone and determining the relative effectiveness of 3 radiotherapy doses (16, 20, and 24 Gy).
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Methods |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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This trial was conducted under a Food and Drug Administration Investigational Device Exemption for a trial of intracoronary radiation therapy. It was approved by the Institutional Review Boards or Ethics Committees and the Radiation Safety Committees of the participating institutions. The study was conducted at the 6 clinical sites listed in the authors’ affiliations. The eligibility requirements are shown in Table 1
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Radiation Delivery System
The intravascular radiation therapy system,
dosimetry, and procedure have been described previously in
detail.6 Briefly, the system consists of 3 components. The
source wire is a 0.018-inch flexible Nitinol wire, with the active
32P source encapsulated in the distal 27 mm
of the wire. The centering balloon catheter is a double-lumen catheter
with a short monorail distal tip for a rapid exchange method of
delivery and a spiral balloon, with nominal diameters of 2.5, 3.0, and
3.5 mm, which centers the source within the lumen while allowing
side branch and distal perfusion (Figure 1).7 The source delivery
unit provides safe storage of the active wire and automated delivery
and retrieval.
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Procedure
After completing the angioplasty procedure, the centering
catheter was advanced to the lesion site, and the markers were
optimally positioned to straddle the balloon/stent-treated lesion
segment. The centering balloon was inflated with normal saline, and a
contrast injection was made through the guiding catheter to assess flow
to the side branches and to the distal artery (Figure 2). An inactive wire was advanced into
the centering catheter, its position was optimized, and it was
withdrawn. Then the study wire (either active or placebo) was advanced
to the same location as the inactive wire and verified
angiographically.
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Dosimetry
The radiation prescription was based on the average of the lumen
diameters at the proximal and distal reference segments, as measured by
intravascular ultrasound or online quantitative coronary
angiography or as determined by the known percutaneous
transluminal coronary angioplasty (PTCA) balloon or stent
sizes. This value was entered into the source delivery unit, which then
used source activity to calculate the dwell time needed to deliver the
specified dose.
Randomization, Follow-Up, and Medication
Each patient was randomized to 1 of 4 radiation treatment
groups: 0, 16, 20, or 24 Gy to 1 mm beyond the lumen surface. Only
the radiation oncologist, medical physicist, and the radiation safety
officer were not blinded to treatment assignment. Clinical
follow-up was obtained at 1, 3, and 6 months. Angiographic follow-up
was mandated after 6 months. All patients received 325 mg of aspirin
for the duration of the study. Ticlopidine (250 mg BID) was prescribed
for 4 weeks after the index procedure for patients who received a
procedural stent.
Quantitative Coronary Angiography
After nitroglycerin administration, angiograms
were obtained in 2 views at baseline (pre-PTCA), after the procedure,
and at 6 months. Procedural and 6-month films were forwarded to the
Core Angiography Laboratory at Baylor College of Medicine and were read
in a blinded fashion using the CAAS II system (Pie Medical). Markers on
the centering catheter identified the location of the radiation zone.
The 6-month angiogram was analyzed with a side-by-side
projection of the radiation treatment catheter to assure accurate
identification of the radiation zone. Target site was defined as the
segment of balloon and stent injury required to treat the target
lesion. Adjacent segments were defined as the segments of artery
outside the target site and extended to 5 mm beyond the radiation
zone (Figure 3). Reference and minimal
lumen diameters (MLD) and percent diameter stenosis of the
target site and adjacent segment were determined. Acute gain, late
lumen loss, and late loss index (expressed as a percent of acute gain)
were calculated for the target site. Binary restenosis was
defined as 50% diameter stenosis on the follow-up angiogram
and was measured for target site alone and for target site plus
adjacent segments.
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End Points
All clinical events were reviewed and adjudicated by an
independent Clinical Events Committee. The primary clinical end point
was the combined short-term (in-hospital) and late (12 months)
rate of major adverse clinical events (MACE). MACE were defined as the
composite of death, myocardial infarction (MI; Q-wave and non–Q-wave),
and target lesion revascularization (TLR; PTCA or
coronary artery bypass grafting) for restenosis
involving the target site. Secondary clinical end points included each
of the individual MACE events, as well as target vessel
revascularization (TVR) for restenosis
involving the target site and adjacent segments. Angiographic end
points were MLD, late lumen loss, late loss index, and binary
restenosis at 6 months.
Statistical Methods
Analysis Population
The primary safety end point of the combined early and late rate
of MACE was analyzed on a per protocol (successful procedure)
basis. Three patients who were enrolled did not receive the randomized
treatment because of equipment difficulties; they were excluded from
analyses because none of them received any portion of the
assigned radiation treatment.
The 3 radiation dose populations (16, 20, and 24 Gy) were pooled. Also,
the 3 lesion types (de novo, PTCA restenosis, and in-stent
restenosis) were pooled. Statistical differences were
considered significant at 
<0.05.
Determination of Safety
The randomization was unbalanced (3:1) to detect any safety
issues that would occur with radiation at a high frequency. Binary
incidence rates, angiographic restenosis, target-related
revascularization or failure, or combined
nonspecific late ischemic end points were tested with
2 or exact contingency table analyses.
Continuous variables were compared by Student’s t
test.
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Results |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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A total of 105 patients were enrolled in the study and had a successful procedure; 25 were assigned to the control group and received a nonradioactive treatment wire (sham procedure), and 26, 27, and 27 patients were assigned to receive 16, 20, and 24 Gy, respectively.
The baseline clinical and angiographic characteristics of the treated
and control patients are shown in Table 2. Overall, 73 patients (70%) had de
novo lesions and 32 (30%) had restenotic lesions, which
included those with in-stent restenosis (24%). The angioplasty
procedure included placement of a new stent(s) in 64 patients
(61%).
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During centering balloon inflation, blood flow to the distal vessel and side branches was observed in 87% and 91% of patients, respectively. Fractionation of the treatment was required in only 9 patients (9%) to relieve ischemia during inflation of the centering balloon.
Source wire activity ranged from 39 to 146 mCi (mean, 70±22 mCi). Dwell time ranged from 1.0 to 9.6 minutes (mean, 4.6±2.0 minutes). The time added to the angioplasty procedure to perform radiotherapy was 12±6 minutes (range, 4 to 31 minutes). The radiation survey reading taken 1 m from the approximate location of the source during active source dwell time was 0.46±0.35 mrem/h (range, 0.04 to 1.52 mrem/h).
The primary clinical end point was combined early (in hospital) and late MACE. In-hospital events occurred in 1 radiotherapy patient (1.3%; non–Q-wave MI) and 1 control patient (4.0%; non–Q-wave MI) (P=NS). No in-hospital death or postprocedure revascularization occurred.
Long-term (12-month) MACE (death, MI, and TLR) occurred in 13 radiotherapy patients (16%) and 6 control patients (24%; P=NS). If TVR is included, MACE occurred in 21 radiotherapy patients (26%) and 8 control patients (32%; P=NS).
The occurrences of individual MACE are shown in Table 3. One patient in the radiotherapy group
(16 Gy) died suddenly 2.5 months after receiving a stent for the
treatment of a restenotic lesion in the right coronary
artery. Ticlopidine was prematurely discontinued 3 weeks after the
procedure because of an allergic reaction. At autopsy, thrombotic
occlusion within and proximal to the stent was noted in the absence of
significant neointimal growth. Two in-hospital
procedure-related non–Q-wave MIs occurred, one in each treatment
group. Seven additional MIs occurred in the radiotherapy group. These
occurred at 5 (non–Q-wave), 23 (Q-wave), 83 (non–Q-wave), 103
(non–Q-wave), 111 (non–Q-wave), 160 (Q-wave) and 188 (non–Q-wave)
days after the index procedure. All 7 posthospitalization MIs were
considered acute occlusive events; 6 were treated with
thrombolytic therapy and 1 by direct PTCA. Angiography,
which was performed in 6 of the 7 patients, showed definite thrombus in
3. No definite thrombus was seen in 3 others whose angiograms were
performed several hours (2 patients) or 3 days (1 patient) after
receiving thrombolytics. Each of these 3 patients had
restenosis involving the adjacent segment. Six of the 7
patients with posthospitalization MIs received new stents at the index
procedure. No late MIs occurred in the control group.
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TLR for restenosis was significantly lower in the radiotherapy group (6%) than in the control group (24%; P<0.05). A trend existed toward a lower incidence of TVR in the radiotherapy patients (21% versus 32%), which was not significant by statistical criteria.
The results of the quantitative coronary angiography
analysis are summarized in Table 4 and Figure 4. At the 6-month follow-up angiographic
examination, late lumen loss was 0.22±0.6 mm for the radiotherapy
patients compared with 1.1±0.7 mm for controls
(P<0.0001), and the late loss index was 11±36% compared
with 55±30% (P<0.00001). No coronary artery
aneurysms or nonhealed dissections were seen on follow-up
angiography.
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Angiographic restenosis (50% diameter stenosis) of
the target site was 8% for radiotherapy patients compared with 39%
for controls (P=0.0012). Restenosis of segments
adjacent to the target site occurred in 11 radiotherapy and 3 control
patients. Overall, restenosis of the target site plus adjacent
segments occurred in 22% of the radiotherapy group and 50% of the
control group (P=0.018).
Results in Stented Arteries
Quantitative coronary angiography showed no significant
differences between patients who received stents (n=50) versus those
who received balloon angioplasty (n=30) in late lumen loss
(0.20±0.50 mm versus 0.25±0.74 mm; P=NS) or in
late loss index (9±28% versus 13±46%; P=NS).
Results in 3 Radiotherapy Dose Groups
In patients with follow-up angiography who received 16 Gy (n=23),
20 Gy (n=25), and 24 Gy (n=25), no significant differences
existed between groups in late lumen loss (0.12±0.49, 0.31±0.79, and
0.23±0.48 mm, respectively; P=NS), or in late loss
index (4±28%, 18±50%, and 10±25%, respectively;
P=NS).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Endovascular radiotherapy has emerged as a promising method for reducing restenosis.1 2 3 4 5 Animal investigations using the porcine coronary artery model of restenosis demonstrate a dramatic inhibition of neointima formation after balloon and stent injury after intravascular
- and
ß-radiation.8 9 10 11 12 13 14 15 16 In a landmark clinical trial,
Teirstein and colleagues2 17 showed a significant
reduction in angiographic and clinical measures of restenosis
in patients undergoing coronary intervention for
restenotic lesions who received -radiation
(192Ir) compared with a control group.
Using a ß-radiation source with more limited penetrability may have
inherent safety advantages over -radiation sources. ß-Radiation,
however, has the potential limitation of lesser penetration of the
artery wall, particularly in stented arteries.18 King et
al,4 in a noncontrolled feasibility trial of ß-radiation
using 90Sr, demonstrated a low late lumen loss
and late loss index compared with historical controls in patients with
de novo lesions treated with balloon angioplasty followed by radiation
with a noncentered source. In clinical practice, however, most
coronary interventions include stent implantation, and many
coronary interventions are repeated in patients presenting
with restenotic lesions.19
The present study was undertaken to explore the clinical advantages of an alternative, catheter-based ß-radiation system that used a readily available isotope (32P), a centering delivery catheter with perfusion capabilities, and an automated source-delivery unit. In addition, enrollment criteria were expanded to include a broader clinical spectrum of coronary disease, including both de novo (70%) and restenotic lesions (30%); the latter included in-stent restenosis (24%). It should also be noted that the protocol did not dictate the type of interventional procedure. This was left to the discretion of the operator and resulted in a new stent placement in 61% of lesions and balloon angioplasty alone in the other 39%.
The study demonstrates the overall safety and feasibility of ß-radiotherapy with this system for the prevention of restenosis. The lack of statistically significant differences in the overall MACE event rates between the 2 groups should not be construed as a negative finding because the study was not powered to show such differences. Individually, the rates of TLR were significantly lower with ß-radiotherapy, and the rates of TVR showed a similarly beneficial trend.
The angiographic end points demonstrate a profound inhibition of
restenosis within the target site in patients receiving
radiotherapy compared with a sham-treated control group. Late lumen
loss and the late loss index were reduced 80% by ß-radiotherapy with
32P. Angiographic restenosis at the
target site was reduced by 79% and the need for
revascularization because of target lesion
restenosis was reduced by 74%. Importantly, no diminution of
effectiveness in arteries in which stents were deployed before
radiotherapy treatment seemed to occur. Further, individual instances
of previously recalcitrant restenotic lesions, which were
prevented from recurring by radiotherapy (Figure 5), underscore the potential utility of
intracoronary radiotherapy to inhibit restenosis.
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A unique centering catheter was used to center the source in the postangioplasty or stented lumen, facilitating specification of a particular dose at a circumferential layer within the artery wall while, at the same time, allowing perfusion to the distal artery and side branches. In this study, 3 doses (16, 20, and 24 Gy), representing a broad therapeutic spectrum, were used. The effectiveness of radiation to inhibit restenosis at the target site was comparably demonstrated for each of the doses used. This finding offers promise that the spectrum of therapeutic efficacy for radiotherapy is potentially quite wide.
A primary objective of this study was to assess the safety of radiotherapy with the system used. In this regard, 105 of 108 treatments (97%), both active and sham, were successfully administered. Fractionation of the treatment due to a reduction in coronary blood flow by the helical centering balloon was required in only 9% of applications. Only 2 patients had procedure-related clinical events (non–Q-wave MI; 1 patient in each group), which were due to stent-related side branch entrapment. Radiation survey readings in the room at the approximate site of the operator in attendance during active source dwell time were below those encountered during fluoroscopy.
Several potential radiation-related issues were identified in this
study. Despite the dramatic inhibition of the restenotic
process at the lesion site, which received the full beam of radiation,
some patients developed narrowing at or adjacent to the edge of the
radiation zone. In most instances in which edge narrowing was observed,
a careful review of the procedural angiograms revealed evidence of
balloon or stent injury that was incompletely covered by the
radiotherapy treatment, which is consistent with the concept of
a targeting error or "geographic miss" as the fundamental cause of
this phenomenon (Figure 6).20 As such,
incorporating a broad margin of treatment beyond the segment of balloon
or stent injury may lessen this phenomenon. In some patients, however,
edge narrowing was observed despite radiation treatment that seemed to
overlap the injury zone appropriately.
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The net effect of edge narrowing was to substantially diminish the overall effectiveness of radiotherapy to inhibit angiographic and clinical measures of restenosis. When angiographic restenosis of the target site alone was analyzed, only 8% of target lesions restenosed. In contrast, when the target site plus adjacent segments was analyzed, the rate of angiographic restenosis in the radiotherapy group increased to 22%. Of note, even with restenosis related to edge narrowing included, the angiographic restenosis rate was still significantly below that observed in the control group (22% versus 50%; P=0.018). Similarly, TLR due to restenosis was needed in only 6% of radiotherapy patients. However, revascularization for restenosis at the target lesion or adjacent segments (TVR) was performed in 21% of radiotherapy patients.
An additional observation of this investigation was the occurrence of
MI in 7 radiotherapy patients between the time of hospital discharge
and 12-month follow-up. No such events occurred in control patients.
All 7 MIs seemed to be acute events, which were treated with
thrombolytic therapy (6 patients) or direct PTCA (1
patient). Six of the 7 patients had received new stents at the index
procedure. These events contributed significantly to the diminution of
clinical benefit that might have been anticipated by the impressive
reduction in angiographic restenosis. A similar incidence of
late thrombosis was recently reported for a group of patients treated
in other - and ß-source trials.21 22 Although the
proximate cause of these late thrombotic events is uncertain, it is
reasonable to speculate that radiotherapy delays the formation of
"protective" neointima, thus affording an opportunity
for exposed stent material or a disrupted lesion to form a nidus for
subsequent coronary thrombosis. Reducing the use of new stents
in patients who are to receive radiotherapy may be an important
strategy to minimize the occurrence of late thrombotic events.
During the time this study was conducted, the standard of care for anti-platelet therapy consisted of aspirin on a continuing basis and ticlopidine for 1 month for stented patients. None of the patients were on ticlopidine at the time a thrombotic event occurred. The possibility that longer-term use of anti-platelet agents would lessen the occurrence of these late thrombotic events is being explored.
Limitations of the Study
This study explored the safety and performance of
ß-radiation with 32P in a broad spectrum of
patients. In view of the limitation in sample size, definitive
conclusions, positive or negative, about the efficacy of this
radiotherapy to prevent restenosis are limited in scope.
Nevertheless, a dramatic reduction of neointimal growth
within the target site was demonstrable for this diverse patient
group.
In a relatively small population of patients, statistically meaningful comparisons of subgroups are not possible. The subgroup analyses were performed to see if any trends were apparent between subgroups. No such trends were noted among dose subgroups. Additionally, stented patients did not seem to be less responsive than nonstented patients to the effects of radiotherapy.
Conclusions
Radiotherapy with a 32P source wire using a
centering catheter method and automated source-delivery unit seems to
be safe and highly effective in reducing neointima within
the target site in patients undergoing coronary angioplasty.
The presence of a metallic stent in the coronary artery did not
seem to limit the effectiveness of ß-radiotherapy to diminish
neointimal growth. There appears to be a wide therapeutic
range of safe and effective dosing.
Two radiotherapy-related problems were identified, arterial narrowing adjacent to the edge of the target site and unexpected late coronary thrombo-occlusive events. The use of longer radiotherapy sources that provide a wide margin of treatment beyond the segment of injury may overcome the problem of edge narrowing. More prolonged use of anti-platelet agents and a reduced use of new stents may minimize the occurrence of late thrombotic events. Subsequent large-scale, multicenter trials incorporating these procedural changes will ultimately determine the overall benefit that can be achieved with ß-radiotherapy in patients with restenosis.
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Acknowledgments |
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The authors wish to express their appreciation to the numerous research coordinators, radiation oncologists, and radiation physicists who assisted in conducting this trial. The secretarial assistance of Ms Dee-Dee Webb is also appreciated. This study was supported by Guidant Vascular Interventions, Santa Clara, Calif.
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Footnotes |
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This article originally appeared Online on July 28, 2000.
Received July 7, 2000; revision received July 18, 2000; accepted July 18, 2000.
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References |
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 E. Minar, M. Schillinger, K. Krueger, and K. Lackner Endovascular Irradiation after Femoropopliteal Angioplasty * Drs Krueger and Lackner respond: Radiology, December 1, 2004; 233(3): 935 - 937. [Full Text] [PDF]
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 D. Choi, S.-K. Kim, S.-H. Choi, Y.-G. Ko, C.-W. Ahn, Y. Jang, S.-K. Lim, H.-C. Lee, and B.-S. Cha Preventative Effects of Rosiglitazone on Restenosis After Coronary Stent Implantation in Patients With Type 2 Diabetes Diabetes Care, November 1, 2004; 27(11): 2654 - 2660. [Abstract] [Full Text] [PDF]
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P. W. Serruys, W. Wijns, G. Sianos, I. de Scheerder, P. A. van den Heuvel, W. Rutsch, H. D. Glogar, C. Macaya, P. H. Materne, S. Veldhof, et al. Direct stenting versus direct stenting followed by centered beta-radiation with intravascular ultrasound-guided dosimetry and long-term anti-platelet treatment: Results of a randomized trial: Beta-radiation Investigation with Direct stenting and Galileo in Europe (BRIDGE) J. Am. Coll. Cardiol., August 4, 2004; 44(3): 528 - 537. [Abstract] [Full Text] [PDF]
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M. Togni, S. Windecker, P. Wenaweser, D. Tueller, A. Kaisaier, W. Maier, B. Meier, and O. M. Hess Deleterious Effect of Coronary Brachytherapy on Vasomotor Response to Exercise Circulation, July 13, 2004; 110(2): 135 - 140. [Abstract] [Full Text] [PDF]
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K. Krueger, M. Zaehringer, M. Bendel, H. Stuetzer, D. Strohe, M. Nolte, D. Wittig, R.-P. Mueller, and K. Lackner De Novo Femoropopliteal Stenoses: Endovascular Gamma Irradiation Following Angioplasty--Angiographic and Clinical Follow-up in a Prospective Randomized Controlled Trial Radiology, May 1, 2004; 231(2): 546 - 554. [Abstract] [Full Text] [PDF]
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M Jaster, V Fuster, P Rosenthal, M Pauschinger, Q-V Tran, D Janssen, W Hinkelbein, P Schwimmbeck, H-P Schultheiss, and U Rauch Catheter based intracoronary brachytherapy leads to increased platelet activation Heart, February 1, 2004; 90(2): 160 - 164. [Abstract] [Full Text] [PDF]
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 C.-L. Hang, M. Fu, B.-T. Hsieh, S. W. Leung, C.-J. Wu, H.-K. Yip, and G. Ting Intracoronary {beta}-Irradiation With Liquid Rhenium-188: Results of the Taiwan Radiation in Prevention of Post-Pure Balloon Angioplasty Restenosis Study Chest, October 1, 2003; 124(4): 1284 - 1293. [Abstract] [Full Text] [PDF]
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P. S. Teirstein and S. King Vascular Radiation in a Drug-Eluting Stent World: It's Not Over Till It's Over Circulation, July 29, 2003; 108(4): 384 - 385. [Full Text] [PDF]
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R. Waksman and J. Weinberger Coronary Brachytherapy in the Drug-Eluting Stent Era: Don't Bury It Alive Circulation, July 29, 2003; 108(4): 386 - 388. [Full Text] [PDF]
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M. Hoher, J. Wohrle, M. Wohlfrom, J. Kamenz, T. Nusser, O. C. Grebe, H. Hanke, M. Kochs, S. N. Reske, V. Hombach, et al. Intracoronary {beta}-Irradiation With a Rhenium-188-Filled Balloon Catheter: A Randomized Trial in Patients With De Novo and Restenotic Lesions Circulation, June 24, 2003; 107(24): 3022 - 3027. [Abstract] [Full Text] [PDF]
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T M Schiele, E Regar, S Silber, E Eeckhout, D Baumgart, W Wijns, A Colombo, W Rutsch, D Meerkin, A Gershlick, et al. Clinical and angiographic acute and follow up results of intracoronary {beta} brachytherapy in saphenous vein bypass grafts: a subgroup analysis of the multicentre European registry of intraluminal coronary {beta} brachytherapy (RENO) Heart, June 1, 2003; 89(6): 640 - 644. [Abstract] [Full Text] [PDF]
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 P. Urban, P. Serruys, D. Baumgart, A. Colombo, S. Silber, E. Eeckhout, A. Gershlick, K. Wegscheider, L. Verhees, R. Bonan, et al. A multicentre European registry of intraluminal coronary beta brachytherapy Eur. Heart J., April 1, 2003; 24(7): 604 - 612. [Abstract] [Full Text] [PDF]
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 S. Sharma, B. Bhambi, W. Nyitray, K. Desai, D. L. Davis, G. Sharma, P. Shukla, C. File, and T. Ishimori Bivalirudin (Angiomax) Use during Intracoronary Brachytherapy May Predispose to Acute Closure Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2003; 8(1): 9 - 15. [Abstract] [PDF]
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 N P Jenkins, B D Prendergast, and M Thomas Drug eluting coronary stents BMJ, December 7, 2002; 325(7376): 1315 - 1316. [Full Text] [PDF]
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R. Seabra-Gomes Intracoronary brachytherapy for restenosis: an efficient technique in the struggle for survival? Eur. Heart J., September 1, 2002; 23(17): 1319 - 1321. [Full Text] [PDF]
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P.W. Serruys, G. Sianos, W. van der Giessen, H.J.R.M. Bonnier, P. Urban, W. Wijns, E. Benit, M. Vandormael, R. Dorr, C. Disco, et al. Intracoronary {beta}-radiation to reduce restenosis after balloon angioplasty and stenting. The Beta Radiation In Europe (BRIE) study Eur. Heart J., September 1, 2002; 23(17): 1351 - 1359. [Abstract] [Full Text] [PDF]
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J. J. Popma, M. Suntharalingam, A. J. Lansky, R. R. Heuser, B. Speiser, P. S. Teirstein, V. Massullo, T. Bass, R. Henderson, S. Silber, et al. Randomized Trial of 90Sr/90Y {beta}-Radiation Versus Placebo Control for Treatment of In-Stent Restenosis Circulation, August 27, 2002; 106(9): 1090 - 1096. [Abstract] [Full Text] [PDF]
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D. E. Kandzari and D. B. Mark Intracoronary Brachytherapy: Time to Sell Short? Circulation, August 6, 2002; 106(6): 646 - 648. [Full Text] [PDF]
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K. Krueger, P. Landwehr, M. Bendel, M. Nolte, H. Stuetzer, R. Bongartz, M. Zaehringer, G. Winnekendonk, A. Gossmann, R.-P. Mueller, et al. Endovascular Gamma Irradiation of Femoropopliteal de Novo Stenoses Immediately after PTA: Interim Results of Prospective Randomized Controlled Trial Radiology, August 1, 2002; 224(2): 519 - 528. [Abstract] [Full Text] [PDF]
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C. di Mario and K. Toutouzas No room for radiant dreams in the real world Eur. Heart J., July 1, 2002; 23(13): 999 - 1001. [Full Text] [PDF]
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L. Gruberg, R. Waksman, A. E. Ajani, H.-S. Kim, R. L. White, E. E. Pinnow, L. F. Satler, A. D. Pichard, K. M. Kent, and J. Lindsay Jr The effect of intracoronary radiation for the treatment of recurrent in-stent restenosis in patients with diabetes mellitus J. Am. Coll. Cardiol., June 19, 2002; 39(12): 1930 - 1936. [Abstract] [Full Text] [PDF]
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M. A. Grise, V. Massullo, S. Jani, J. J. Popma, R. J. Russo, R. A. Schatz, E. M. Guarneri, S. Steuterman, D. A. Cloutier, M. B. Leon, et al. Five-Year Clinical Follow-Up After Intracoronary Radiation: Results of a Randomized Clinical Trial Circulation, June 11, 2002; 105(23): 2737 - 2740. [Abstract] [Full Text] [PDF]
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C. Hanefeld, S. Amirie, D. Borchardt, P. Grewe, K.-M. Muller, M. Kissler, and A. Mugge Dosimetric Measurements in Isolated Human Coronary Arteries: Comparison of Commercially Available Iridium192 With Strontium/Yttrium90 Emitters Circulation, May 28, 2002; 105(21): 2493 - 2496. [Abstract] [Full Text] [PDF]
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H. C. Lowe, S. N. Oesterle, and L. M. Khachigian Coronary in-stent restenosis: Current status and future strategies J. Am. Coll. Cardiol., January 16, 2002; 39(2): 183 - 193. [Abstract] [Full Text] [PDF]
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 G. Schnyder, M. Roffi, R. Pin, Y. Flammer, H. Lange, F. R. Eberli, B. Meier, Z. G. Turi, and O. M. Hess Decreased Rate of Coronary Restenosis after Lowering of Plasma Homocysteine Levels N. Engl. J. Med., November 29, 2001; 345(22): 1593 - 1600. [Abstract] [Full Text] [PDF]
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P. S. Teirstein and R. E. Kuntz New Frontiers in Interventional Cardiology: Intravascular Radiation to Prevent Restenosis Circulation, November 20, 2001; 104(21): 2620 - 2626. [Full Text] [PDF]
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T. A. Fischell and R. Virmani Intracoronary Brachytherapy in the Porcine Model: A Different Animal Circulation, November 13, 2001; 104(20): 2388 - 2390. [Full Text] [PDF]
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L. Gruberg, R. Waksman, A. E. Ajani, H.-S. Kim, R. L. White, E. Pinnow, R. Deible, L. F. Satler, A. D. Pichard, K. K. Kent, et al. The effect of intracoronary radiation for the treatment of recurrent in-stent restenosis in patients with chronic renal failure J. Am. Coll. Cardiol., October 1, 2001; 38(4): 1049 - 1053. [Abstract] [Full Text] [PDF]
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G. S. Mintz, N. J. Weissman, and P. J. Fitzgerald Intravascular Ultrasound Assessment of the Mechanisms and Results of Brachytherapy Circulation, September 11, 2001; 104(11): 1320 - 1325. [Full Text] [PDF]
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G. Sianos, I. P. Kay, M. A. Costa, E. Regar, K. Kozuma, P. J. de Feyter, E. Boersma, C. Disco, and P. W. Serruys Geographical miss during catheter-based intracoronary beta-radiation: incidence and implications in the BRIE study J. Am. Coll. Cardiol., August 1, 2001; 38(2): 415 - 420. [Abstract] [Full Text] [PDF]
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R. Seabra-Gomes Radioactive stents to reduce restenosis: time for an epitaph? Eur. Heart J., April 2, 2001; 22(8): 621 - 623. [PDF]
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V. Verin, Y. Popowski, B. de Bruyne, D. Baumgart, W. Sauerwein, M. Lins, G. Kovacs, M. Thomas, F. Calman, C. Disco, et al. Endoluminal Beta-Radiation Therapy for the Prevention of Coronary Restenosis after Balloon Angioplasty N. Engl. J. Med., January 25, 2001; 344(4): 243 - 249. [Abstract] [Full Text] [PDF]
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R. Sheppard and M. J. Eisenberg Intracoronary Radiotherapy for Restenosis N. Engl. J. Med., January 25, 2001; 344(4): 295 - 297. [Full Text] [PDF]
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 H. C. Lowe, R. G. Fahmy, M. M. Kavurma, A. Baker, C. N. Chesterman, and L. M. Khachigian Catalytic Oligodeoxynucleotides Define a Key Regulatory Role for Early Growth Response Factor-1 in the Porcine Model of Coronary In-Stent Restenosis Circ. Res., October 12, 2001; 89(8): 670 - 677. [Abstract] [Full Text] [PDF]
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