UvA-DARE is a service provided by the library of the University of Amsterdam (http
s
://dare.uva.nl)
UvA-DARE (Digital Academic Repository)
A randomized trial comparing conventional and endovascular repair of
abdominal aortic aneurysms
Prinssen, M.; Verhoeven, E.L.G.; Buth, J.; Cuypers, Ph.W.M.; Sambeek, M.R.H.M.; Balm, R.;
Buskens, E.; Grobbee, D.E.; Blankensteijn, J.D.
DOI
10.1056/NEJMoa042002
Publication date
2004
Published in
The New England journal of medicine
Link to publication
Citation for published version (APA):
Prinssen, M., Verhoeven, E. L. G., Buth, J., Cuypers, P. W. M., Sambeek, M. R. H. M., Balm,
R., Buskens, E., Grobbee, D. E., & Blankensteijn, J. D. (2004). A randomized trial comparing
conventional and endovascular repair of abdominal aortic aneurysms.
The New England
journal of medicine
,
351
(16), 1607-1618. https://doi.org/10.1056/NEJMoa042002
General rights
It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s)
and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open
content license (like Creative Commons).
Disclaimer/Complaints regulations
If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please
let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material
inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter
to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You
will be contacted as soon as possible.
Download date:09 Aug 2022
n engl j med
351;16
www.nejm.org october
14, 2004
1607
The
new england
journal
of
medicine
established in 1812
october
14
,
2004
vol. 351 no. 16
A Randomized Trial Comparing Conventional
and Endovascular Repair of Abdominal Aortic Aneurysms
Monique Prinssen, M.D., Eric L.G. Verhoeven, M.D., Jaap Buth, M.D.,
Philippe W.M. Cuypers, M.D., Marc R.H.M. van Sambeek, M.D., Ron Balm, M.D.,
Erik Buskens, M.D., Diederick E. Grobbee, M.D., and Jan D. Blankensteijn, M.D.,
for the Dutch Randomized Endovascular Aneurysm Management (DREAM)Trial Group*
abstract
From the Division of Vascular Surgery, De-
partment of Surgery (M.P., J.D.B.), and the
Julius Center for Health Sciences and Pri-
mary Care (E.B., D.E.G.), University Medi-
cal Center, Utrecht; the Division of Vascular
Surgery, Department of Surgery, Academ-
ic Hospital, Groningen (E.L.G.V.); the De-
partment of Surgery, Catharina Hospital,
Eindhoven (J.B., P.W.M.C.);
the Division
of Vascular Surgery, Department of Sur-
gery, Erasmus Medical Center, Rotterdam
(M.R.H.M.S.); the Division of Vascular Sur-
gery, Department of Surgery, Academic
Medical Center, Amsterdam (R.B.); and
the Department of Vascular Surgery, Rad-
boud University, Nijmegen Medical Cen-
ter, Nijmegen (J.D.B.) — all in the Nether-
lands. Address reprint requests to Dr.
Blankensteijn at the Department of Vascu-
lar Surgery (410), Radboud University,
Nijmegen Medical Center, P.O. Box 9101,
6500 HB Nijmegen, the Netherlands, or at
j.blankensteijn@chir.umcn.nl.
*The members of the DREAM Trial Group
are listed in the Appendix.
N Engl J Med 2004;351:1607-18.
Copyright © 2004 Massachusetts Medical Society.
background
Although the initial results of endovascular repair of abdominal aortic aneurysms were
promising, current evidence from controlled studies does not convincingly show a re-
duction in 30-day mortality relative to that achieved with open repair.
methods
We conducted a multicenter, randomized trial comparing open repair with endovascu-
lar repair in 345 patients who had received a diagnosis of abdominal aortic aneurysm
of at least 5 cm in diameter and who were considered suitable candidates for both tech-
niques. The outcome events analyzed were operative (30-day) mortality and two com-
posite end points of operative mortality and severe complications and operative mor-
tality and moderate or severe complications.
results
The operative mortality rate was 4.6 percent in the open-repair group (8 of 174 pa-
tients; 95 percent confidence interval, 2.0 to 8.9 percent) and 1.2 percent in the endo-
vascular-repair group (2 of 171 patients; 95 percent confidence interval, 0.1 to 4.2 per-
cent), resulting in a risk ratio of 3.9 (95 percent confidence interval, 0.9 to 32.9). The
combined rate of operative mortality and severe complications was 9.8 percent in the
open-repair group (17 of 174 patients; 95 percent confidence interval, 5.8 to 15.2 per-
cent) and 4.7 percent in the endovascular-repair group (8 of 171 patients; 95 percent
confidence interval, 2.0 to 9.0 percent), resulting in a risk ratio of 2.1 (95 percent con-
fidence interval, 0.9 to 5.4).
conclusions
On the basis of the overall results of this trial, endovascular repair is preferable to open
repair in patients who have an abdominal aortic aneurysm that is at least 5 cm in diam-
eter. Long-term follow-up is needed to determine whether this advantage is sustained.
Copyright © 2004 Massachusetts Medical Society. All rights reserved.
Downloaded from www.nejm.org at UNIVERSITEIT VAN AMSTERDAM on December 18, 2006 .
n engl j med
351;16
www.nejm.org october
14
,
2004
The
new england journal
of
medicine
1608
lective surgical repair is indicat-
ed in patients with a large abdominal aor-
tic aneurysm. The threshold for surgery
is still a subject of debate but varies between 5.0
and 5.5 cm in diameter.
1-4
Endovascular repair, pio-
neered by Parodi and Volodos in the early 1990s, is
a less invasive alternative to conventional open re-
pair.
5,6
Endovascular repair usually involves two
small incisions made in the groin to expose the fem-
oral arteries. With the use of guidewires, catheters,
and specially designed introducer systems, a so-
called endograft is assembled inside the abdomi-
nal aortic aneurysm under fluoroscopic guidance,
thus excluding the aneurysm sac without opening
the abdomen.
From its inception, endovascular repair has been
used in patients for whom open repair poses a high
risk. At the same time, patients with relatively few
coexisting conditions are more likely to meet the
anatomical criteria for endovascular repair, includ-
ing the presence of a suitable infrarenal aortic neck
and absence of severe aortoiliac tortuosity and cal-
cification in the arterial wall.
7
These factors lead to
selection in retrospective analyses and uncontrolled
prospective evaluations and make an unbiased as-
sessment of the benefits and risks of the two tech-
niques problematic.
8-15
Although the initial results of endovascular re-
pair were promising and the less invasive nature of
the procedure is appealing to many patients and
physicians, evidence is needed that demonstrates
the superiority of this approach over open repair,
as are conclusive data on cost-effectiveness.
16-18
We conducted a multicenter, randomized trial —
the Dutch Randomized Endovascular Aneurysm
Management (DREAM) trial — to compare opera-
tive mortality and complications and other out-
come events after elective open repair and endovas-
cular repair.
study design and patients
The design and methods of the trial have been de-
scribed in detail elsewhere.
19
In brief, patients re-
ferred to surgery clinics at 24 centers in the Nether-
lands and 4 centers in Belgium who had received
a diagnosis of an abdominal aortic aneurysm of at
least 5 cm in diameter and who were considered
suitable candidates for both techniques were ran-
domly assigned to undergo open or endovascular
repair, after giving written informed consent. A pa-
tient’s suitability for endovascular repair was pri-
marily determined by means of endograft-depen-
dent anatomical criteria. A patient’s suitability for
open repair was determined by an internist or car-
diologist. Patients who needed to undergo emergen-
cy aneurysm repair were excluded from the study,
as were patients with inflammatory aneurysms,
anatomical variations, connective-tissue disease,
a history of organ transplantations, or a life expect-
ancy of less than two years. The study was per-
formed according to the principles of the Declara-
tion of Helsinki, and the institutional review board
of each participating hospital approved the proto-
col. Randomization was carried out centrally by
means of a computer-generated permuted-block
sequence and stratified according to study center
in blocks of four patients.
An independent data-monitoring and ethics
committee decided whether to continue the trial on
the basis of a single interim analysis of the 30-day
end points performed after half the required num-
ber of patients had been enrolled. In addition, se-
quential monitoring was used to monitor the inci-
dence of death from all causes and all moderate
and severe complications (not just those at 30 days)
in order to safeguard against divergent outcomes
beyond the perioperative period — for instance, as
a result of endograft failure.
20
surgical techniques
All repairs were carried out by surgical teams that
had performed at least five endovascular proce-
dures. Surgical teams that had performed less than
20 procedures were required to have an experienced
proctor assist them during the procedure. Only en-
dovascular devices that had been approved by the
U.S. Food and Drug Administration (FDA) or that
had an Investigational Device Exemption or Con-
formité Européen mark were allowed in the study.
Endovascular repair typically involves small inci-
sions in the groin to expose both femoral arteries,
although some surgeons prefer a total percutane-
ous approach. The endograft is composed of fabric
and metal stents and comes loaded in a specially
designed delivery system. Under fluoroscopic guid-
ance, this introducer system is fed through the iliac
arteries by means of catheters and guidewires until
the endograft is positioned correctly at the top and
bottom of the aneurysmal segment of the aorta.
Removal of the introducer system allows barbs or
other fixing devices to attach to the aortic wall and
hold the graft firmly in place, excluding blood flow
e
methods
Copyright © 2004 Massachusetts Medical Society. All rights reserved.
Downloaded from www.nejm.org at UNIVERSITEIT VAN AMSTERDAM on December 18, 2006 .
n engl j med
351;16
www.nejm.org october
14, 2004
conventional versus endovascular repair of abdominal aortic aneurysms
1609
from the aneurysm sac and removing pressure from
the aneurysmal wall. The exposure and aneurysm-
repair technique used for open repair was at the sur-
geon’s discretion.
end points
Complications were classified and graded accord-
ing to the reporting standards of the Ad Hoc Com-
mittee for Standardized Reporting Practices in
Vascular Surgery of the Society for Vascular Sur-
gery/International Society for Cardiovascular Sur-
gery.
21,22
Three classes of complications (systemic,
local–nonvascular, and local–vascular or implant-
related) and three grades of severity (mild, moder-
ate, and severe) were used. Mild complications
were not considered in this analysis.
An outcome adjudication committee, consisting
of five vascular surgeons, assessed the class and
severity of each complication in a blinded fashion
and independently from each other. Disagreements
were resolved in a plenary consensus meeting. The
primary end point was a composite of operative
mortality and moderate or severe complications.
Operative complications were defined as those that
occurred within 30 days after surgery or more than
30 days after surgery but during the same admis-
sion (in-hospital mortality and complications). Oth-
er outcome events analyzed were operative mortal-
ity and the combination of operative mortality and
severe complications.
statistical analysis
The trial was designed to have 80 percent power to
show a reduction of 50 percent in the primary end
point at the two-sided 5 percent level with endovas-
cular repair, as compared with open repair. The in-
cidence of the primary end point in the open-repair
group was expected to be 20 percent. Four hundred
patients were required.
All analyses were based on all randomized pa-
tients who underwent aneurysm repair. Patients
were classified according to the original random-
ized allocation in all analyses. The risk of a compli-
cation after open repair was compared with that
after endovascular repair, and the results are pre-
sented as risk ratios and exact 95 percent confi-
dence intervals, derived with the use of StatXact
software (version 6.1, Cytel Software). Means (±SD)
together with medians and interquartile ranges
were used to describe continuous variables. Fre-
quencies and exact 95 percent confidence intervals
were calculated for categorical variables. Differenc-
es between treatment groups were evaluated with
the use of the Mann–Whitney U test for continuous
variables or Fisher’s exact test for proportions. All
reported P values are two-sided and are not adjust-
ed for multiple testing.
The study protocol specified that recruitment
would end by September 2003, with the enrollment
of 400 patients, and that the study would be com-
pleted in January 2004. After negotiations with the
sponsor of the study (the Health Insurance Council
of the Netherlands) about a possible extension,
three extra months were allowed, resulting in an
eventual enrollment that was 12 percent lower than
expected.
The corresponding author had full responsibil-
ity for the conduct of the trial, had full access to all
the data, and controlled the decision to publish.
The sponsor of the study had no role in the study
design.
characteristics of the patients
and treatment assignments
Between November 2000 and December 2003, 351
patients were randomly assigned to undergo either
open repair or endovascular repair (Fig. 1). Six pa-
tients did not undergo aneurysm repair after ran-
domization: four declined treatment (three assigned
to open repair and one to endovascular repair), one
died from a ruptured abdominal aortic aneurysm
before undergoing open repair, and one died from
pneumonia before undergoing endovascular repair.
The remaining 345 patients composed the treat-
ment groups: 174 patients in the open-repair group
and 171 in the endovascular-repair group.
The baseline characteristics of the patients and
aneurysms are shown in Table 1.
23
Demographic
characteristics, coexisting conditions, cardiovas-
cular risk profiles, the distribution of American So-
ciety of Anesthesiologists classifications, and the
characteristics of the aneurysm were similar in the
two groups.
There were six crossovers: five patients who
were randomly assigned to undergo open repair
underwent endovascular repair, and one patient
assigned to endovascular repair underwent open
repair. Overall, in 96.6 percent of patients (339 of
351), the operation was started according to the
randomized assignment. The median interval be-
tween randomization and surgery was 39 days in
both the open-repair group (range, 4 to 260) and
results
Copyright © 2004 Massachusetts Medical Society. All rights reserved.
Downloaded from www.nejm.org at UNIVERSITEIT VAN AMSTERDAM on December 18, 2006 .
n engl j med
351;16
www.nejm.org october
14
,
2004
The
new england journal
of
medicine
1610
the endovascular-repair group (range, 1 to 183;
P=0.76).
surgical and postoperative data
Characteristics of the aneurysm-repair procedures
are shown in Table 2. In three patients who were
randomly assigned to undergo endovascular re-
pair, the procedure was converted intraoperatively
to an open procedure owing to access problems in
two and failed deployment in one. In one patient,
who was randomly assigned to open repair and who
had crossed over to endovascular repair, the proce-
dure was aborted owing to access problems. The
aneurysm was left untreated (Fig. 1).
General anesthesia was used in 98.3 percent of
patients in the open-repair group (in all except three
of the five patients who crossed over to endovas-
cular repair) and in 54.9 percent of patients in the
endovascular-repair group (P<0.001). An aorto-
aortic (tube) graft was used in 59.8 percent of
open repairs and in 1.8 percent of endovascular
repairs (P<0.001). At least one internal iliac artery
was sacrificed (intentionally or unintentionally)
in 4.0 percent of patients in the open-repair group,
Figure 1. Randomization, Treatment, and Analysis of Outcomes.
351 Patients randomized
178 Assigned to open repair 173 Assigned to endovascular repair
174 Included in analysis as randomized 171 Included in analysis as randomized
Open repair started in 170
Endovascular repair started in 175
Open repair completed in 173 Endovascular repair completed in 171
4 Did not undergo
aneurysm repair
3 Declined
1 Died
5 Underwent
endovascular
repair
1 Underwent
open repair
3 Conversions
to open repair
1 Procedure aborted
(crossover from
open repair)
2 Did not undergo
aneurysm repair
1 Declined
1 Died
Copyright © 2004 Massachusetts Medical Society. All rights reserved.
Downloaded from www.nejm.org at UNIVERSITEIT VAN AMSTERDAM on December 18, 2006 .
