Endovascular repair compared with surveillance for patients with small abdominal aortic aneurysms.
ABSTRACT Although repair of large abdominal aortic aneurysms (AAAs) is well accepted, randomized clinical trials have failed to demonstrate benefit for early surgical repair of small aneurysms compared with surveillance. Endovascular repair has been shown to be safer than open surgical repair in patients with large aneurysms, prompting a randomized trial of early endovascular repair vs surveillance in patients with small aneurysms.
We randomly assigned 728 patients (13.3% women; mean age, 71 +/- 8 years) with 4 to 5 cm AAAs to early endovascular repair (366 patients) or ultrasound surveillance (362 patients). Rupture or aneurysm-related death and overall mortality in the two groups were compared during a mean follow-up of 20 +/- 12 months.
Among patients randomized to treatment, 89% underwent aneurysm repair. Among patients randomized to surveillance, 31% underwent aneurysm repair during the course of the study. After a mean follow-up of 20 +/- 12 months (range, 0-41 months), 15 deaths had occurred in each group (4.1%). The unadjusted hazard ratio (95% confidence interval) for mortality after early endovascular repair was 1.01 (0.49-2.07, P = .98). Aneurysm rupture or aneurysm-related death occurred in two patients in each group (0.6%). The unadjusted hazard ratio was 0.99 (0.14-7.06, P = .99) for early endovascular repair.
Early treatment with endovascular repair and rigorous surveillance with selective aneurysm treatment as indicated both appear to be safe alternatives for patients with small AAAs, protecting the patient from rupture or aneurysm-related death for at least 3 years.
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ABSTRACT: Aortic aneurysms are associated with coronary artery ectasia (CAE). However, the relation between the extent of CAE and coronary blood flow in patients with aortic aneurysms is not fully understood. This study was undertaken to assess the angiographic characteristics and effects of the topographical extent of CAE on coronary blood flow in patients with aortic aneurysms. This study consisted of 93 consecutive patients with aortic aneurysms (AA group) and 79 patients without aortic aneurysms who had angiographically normal coronary arteries as the control group (Control group). Coronary flow velocity was determined using the thrombolysis in myocardial infarction frame count (TFC) and the topographical extent of CAE was assessed. In the AA group, 43 patients (46.2 %) had significant coronary artery stenosis and 37 patients (40.2 %) had diffuse CAE. TFC was significantly higher in the AA group than in the control group in all 3 coronary arteries. Furthermore, mean corrected TFC (CTFC) was significantly higher in the AA group than in the control group (40.1 ± 10.7 vs. 25.8 ± 6.5, p < 0.001). In the AA group, mean CTFC in patients with diffuse CAE was significantly higher than that in patients with segmental CAE (50.2 ± 8.7 vs. 33.6 ± 5.2, p < 0.001). The mean CTFC correlated positively with the topographical extent of CAE. Many patients with aortic aneurysms were accompanied with angiographic coronary artery stenosis and CAE. Furthermore, patients with aortic aneurysms had higher CTFC than those without aortic aneurysms and it was primarily driven by more frequent prevalence of diffuse CAE.Heart and vessels. 07/2014;
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ABSTRACT: To assess whether survival differences exist between patients undergoing immediate open repair vs surveillance with selective repair for 4.0- to 5.4-cm abdominal aortic aneurysms (AAAs) and whether these differences vary by diameter, within sexes, or overall. The study cohort included 2226 patients randomized to immediate repair or surveillance for the UK Small Aneurysm Trial (September 1, 1991, through July 31, 1998; follow-up, 2.6-6.9 years) or the Aneurysm Detection and Management trial (August 1, 1992, through July 31, 2000; follow-up, 3.5-8.0 years). Survival differences were assessed with proportional hazard models, adjusted for a comprehensive array of clinical and nonclinical risk factors. Interaction between treatment and AAA size was added to the model to assess whether the effect of immediate open repair vs surveillance varied by AAA size. The adjusted analysis revealed no statistically significant survival difference between immediate open repair and surveillance patients (hazard ratio [HR], 0.99; 95% CI, 0.83-1.18; mean follow-up time, 1921 days for both study groups). This lack of treatment effect persisted when men (HR, 1.01; 95% CI, 0.84-1.21) and women (HR, 0.96; 95% CI, 0.49-1.86) were examined separately and did not vary by AAA size (P=.39 for the entire cohort and P=.24 for women). Immediate open repair offered no significant survival benefit, even in patients with the largest AAAs and highest risk of rupture. Because recent trials failed to find a survival benefit of immediate endovascular repair over surveillance for small asymptomatic AAAs, our findings suggest that the gray area of first-line management for these patients should be resolved in favor of surveillance.Mayo Clinic Proceedings 09/2013; 88(9):910-9. · 5.79 Impact Factor
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ABSTRACT: Adoption of healthcare innovations frequently outpaces the evidence of effectiveness. Endovascular repair (EVAR) for abdominal aortic aneurysms in the USA demonstrates how comparative effectiveness research without evidence-based reimbursement changes may fail to influence clinical practice. Randomized controlled trials for small abdominal aortic aneurysms demonstrate no lasting benefits of EVAR or open surgical repair (OSR) compared with surveillance, and for large abdominal aortic aneurysms demonstrate no lasting survival benefit of EVAR over OSR, and do show poorer durability and higher costs for EVAR. Nonetheless, >50% of elective abdominal aortic aneurysm repairs in the USA use EVAR. Factors that may be driving the high use of EVAR include patient preference, surgeons' desire to appear 'up-to-date' in the procedures they offer, higher hourly surgeon reimbursement for EVAR than OSR, and the expansion of physician specialties able to perform abdominal aortic aneurysm repair from only vascular surgeons with OSR, to vascular surgeons and interventional radiologists/cardiologists with EVAR. By comparison, in Canada, where government health insurance restricts EVAR coverage to high surgical risk patients, only approximately 25% of abdominal aortic aneurysm repairs are performed using EVAR. Country-specific cost studies and a prospective population-based study collecting detailed clinical data to identify patient subgroups that truly benefit from a particular management strategy are needed to inform policy regarding EVAR availability and reimbursement.Journal of comparative effectiveness research. 01/2012; 1(1):31-44.
CLINICAL RESEARCH STUDIES
From the Society for Vascular Surgery
Endovascular repair compared with surveillance
for patients with small abdominal aortic aneurysms
Kenneth Ouriel, MD,aDaniel G. Clair, MD,bK. Craig Kent, MD,cand Christopher K. Zarins, MD,dfor
the Positive Impact of Endovascular Options for treating Aneurysms Early (PIVOTAL) Investigators,
New York, NY; Cleveland, Ohio; Madison, Wisc; and Palo Alto, Calif
Background: Although repair of large abdominal aortic aneurysms (AAAs) is well accepted, randomized clinical trials have
failed to demonstrate benefit for early surgical repair of small aneurysms compared with surveillance. Endovascular repair
has been shown to be safer than open surgical repair in patients with large aneurysms, prompting a randomized trial of
early endovascular repair vs surveillance in patients with small aneurysms.
Methods: We randomly assigned 728 patients (13.3% women; mean age, 71 ? 8 years) with 4 to 5 cm AAAs to early
endovascular repair (366 patients) or ultrasound surveillance (362 patients). Rupture or aneurysm-related death and
overall mortality in the two groups were compared during a mean follow-up of 20 ? 12 months.
Results: Among patients randomized to treatment, 89% underwent aneurysm repair. Among patients randomized to
surveillance, 31% underwent aneurysm repair during the course of the study. After a mean follow-up of 20 ? 12 months
(range, 0-41 months), 15 deaths had occurred in each group (4.1%). The unadjusted hazard ratio (95% confidence
interval) for mortality after early endovascular repair was 1.01 (0.49-2.07, P ? .98). Aneurysm rupture or aneurysm-
related death occurred in two patients in each group (0.6%). The unadjusted hazard ratio was 0.99 (0.14-7.06, P ? .99)
for early endovascular repair.
Conclusions: Early treatment with endovascular repair and rigorous surveillance with selective aneurysm treatment as
indicated both appear to be safe alternatives for patients with small AAAs, protecting the patient from rupture or
aneurysm-related death for at least 3 years. (J Vasc Surg 2010;51:1081-7.)
an event strongly correlated with the diameter of the aneu-
rysm.1The mortality from aneurysm repair itself, however,
can be significant.2Operative risk must be balanced against
the risk of rupture when deciding between repair and
observation. Repair is indicated in most patients with larger
aneurysms, but two prospective randomized clinical trials
failed to detect benefits of early open surgical repair com-
pared with surveillance in patients with small aneurysms
of ?5.5 cm in diameter.3,4
Operative mortality rates of 2.7% and 5.8% in these two
trials raised the question of whether a procedure with lower
operative mortality might provide benefit compared with ob-
aneurysm repair (EVAR) has been shown to have a lower
perioperative mortality rate than open surgical repair.5-7The
Positive Impact of Endovascular Options for Treating Aneu-
rysms Early (PIVOTAL) trial was organized to determine
related death compared with surveillance in patients with
small (4- to 5-cm) abdominal aortic aneurysms (AAAs). Here
we report the early results of this first randomized clinical trial
comparing the two modalities.
Study design. The trial was approved by the human
subject research committees of each participating center. The
trial management was coordinated centrally by a steering
committee, and the safety of the study was monitored by an
independent patient safety committee that met biannually.
Eligible patients were aged between 40 and 90 years,
with infrarenal AAAs between 4.0 and 5.0 cm in diameter
by computed tomography (CT) performed ?3 months of
screening. Patients were excluded from the study if they
From the Division of Vascular Surgery, Columbia University and NewYork-
Presbyterian Hospital;aHeart and Vascular Institute, Cleveland Clinic;b
Department of Surgery, University of Wisconsin, Madison;cand Division
of Vascular Surgery, Stanford University.d
Competition of interest: Christopher Zairns and Daniel Clair receive re-
search funding from Medtronic and are consultants for the company.
Reprint requests: Kenneth Ouriel, MD, NewYork-Presbyterian Hospital, 14
E 60th St, No. 1201, New York, NY 10022 (e-mail: email@example.com).
The editors and reviewers of this article have no relevant financial relationships
to disclose per the JVS policy that requires reviewers to decline review of any
manuscript for which they may have a competition of interest.
Copyright © 2010 by the Society for Vascular Surgery.
had evidence of symptoms referable to the aneurysm, an
abdominal or thoracic aortic repair, an aneurysm originat-
ing ?1.0 cm from the most distal main renal artery, life
expectancy of ?3 years, inability to provide informed con-
sent, predicted noncompliance with the protocol, Society
for Vascular Surgery (SVS) score ?2, with the exception of
age and controlled hypertension, baseline serum creatinine
level ?2.5 mg/dL, or when the patient did not meet the
indications for use for the endograft device. The Cleveland
Clinic coordinating center managed the study and was
responsible for randomization, study patient monitoring,
data acquisition, and data analysis. The study is registered
on clinicaltrials.gov (NCT00444821).
Randomization, treatment, and follow-up. The
randomization procedure was created with equal probabil-
ity of assignment to each of the treatment groups by means
of a computer-generated random-number code that was
maintained at the coordinating center. Patients assigned to
early EVAR underwent aneurysm repair ?30 days of ran-
(Medtronic, Santa Rosa, Calif). Before April 16, 2008, the
implanted devices were the commercially available AneuRx
device. After approval of the Talent device on April 2008,
investigators could choose between the two. Follow-up
analyses were scheduled for 1 month, 6 months, and every
6 months thereafter for a minimum of 36 months to a
maximum of 60 months after operation. Imaging studies
were scheduled for the 1-month, 6-month, and yearly visits
and included CT scan with contrast, magnetic resonance
scan, or a CT without contrast plus a duplex ultrasound
Individuals in the surveillance group were scheduled to
undergo assessments every 6 months for a minimum of 36
months up to 60 months after randomization. An ultrasound
of the aneurysm. Patients were offered aneurysm repair when
symptoms thought referable to the aneurysm developed,
when the diameter of the aneurysm reached 5.5 cm, or when
the aneurysm enlarged ?0.5 cm between any two 6-month
or open surgical repair was advised.
Outcome measures. The primary objective of the trial
was to determine whether early endovascular repair of
aneurysms 4.0 to 5.0 cm in diameter is superior to surveil-
lance with respect to the frequency of rupture or aneurysm-
related death. The primary end point was the composite
end point of rupture or aneurysm-related death, assessed
through 3 years after randomization. Death was considered
to be aneurysm-related when it occurred as a result of
rupture or when it occurred ?30 days of any operative
procedure for aneurysm repair, whether the procedure was
the primary endovascular or open repair, or a secondary
Statistical analysis. The sample size was based on the
primary outcome of time to rupture or aneurysm-related
death. The event rate for the composite outcome was esti-
mated to be 1.7% per year in the surveillance group and 0.7%
in the EVAR group corresponding to a hazard ratio of 0.42
(0.71/1.70) for surveillance vs early EVAR.3,8,9Sample size
calculations assumed that the primary outcome would be
accrual time, and an 18% loss to follow-up that would follow
an exponential distribution. These estimates suggested that
1050 total patients, or 525 per group, would be necessary to
detect a hazard ratio of ?0.42 with 80% power at a signifi-
cance level of 0.05. The estimates also assumed a constant
hazard over time, but the actual analyses would account for
nonconstant hazard in either or both groups.
Analyses of the primary end point and overall mortality
were performed on an intent-to-treat basis using the log-
rank test. Differences in the risk of end points between
treatment groups were described using hazard ratios from
Cox models. Kaplan-Meier analysis was used to estimate
rates of other events during follow-up. Categoric factors
were compared between treatment groups using ?2or
Fisher’s exact tests, and continuous measures were com-
pared using t tests. Analyses were performed using Stat-
View 9.1 software (SAS Institute, Cary, NC), and all com-
parisons assumed a .05 significance level.
Study group. Among 4665 patients screened, 728
(15.6%) were randomized (Fig 1). Of the 631 men (86.7%)
and 97 women (13.3%), 366 were assigned to early endo-
vascular repair and 362 to ultrasound surveillance. The
mean initial diameter was 4.5 ? 0.3 cm in both groups.
Mean ages were 70.5 ? 7.8 years for patients assigned to
the early EVAR and 70.5 ? 7.7 years for those assigned to
surveillance. Other baseline characteristics are listed in Ta-
ble I. The only significant difference between the two
treatment arms was a higher rate of neurologic disease in
the early repair group (P ? .03). The mean follow-up was
20 ? 12 months (range, 0-41 months) in each treatment
Aneurysm repair. Patients assigned to the early EVAR
treatment arm underwent aneurysm repair a mean of 29.5
days (95% confidence interval [CI], 25-34 days) days after
Fig 1. Flow chart shows patients, randomization, and out-
JOURNAL OF VASCULAR SURGERY
1082 Ouriel et al
entry into the study. Among 322 patients in the early repair
group who underwent an attempt at endovascular repair
with a protocol device and within the specified time win-
dow, 321 (99.7%) had successful delivery and deployment.
Among the 40 patients who did not receive the specified
therapy, 6 underwent repair outside of the 30-day window
after randomization, 9 were withdrawn at the patient’s
request, 10 were withdrawn by the treating physician for
deteriorating health status between randomization and
scheduled repair, and 2 were treated with an endograft
device that was not in the protocol. The reasons for nonre-
pair in the remaining 13 patients were unspecified. Data
outlining the outcome measures in the two groups are
listed in Table II.
Endovascular procedures averaged 125 minutes in du-
ration (95% CI, 118-132 minutes). The estimated blood
loss of the procedures was 254 mL (95% CI, 225-283 mL).
The length of hospital stay averaged 1.6 days (95% CI,
1.5-1.7 days). Graft limb thrombosis occurred in 18 pa-
tients through one year, with similar frequency in the
early-EVAR group (13 patients, 4.8%) and the surveillance
group (5 patients, 5.8%). An endoleak was documented in
36 patients (11.9%) at 30 days and in 72 (26%) at some
time ?1 year after the initial procedure. After repair, aneu-
rysm enlargement by ?0.5 cm was observed in 15 patients
(5.7%) at 1 year of follow-up.
In the surveillance arm, 112 patients (30.9%) under-
went aneurysm repair (Fig 2). The average time from
randomization to repair was 370 days, and the average size
of the aneurysms at the last imaging report before repair
underwent EVAR and 3 (2.7%) had an open surgical repair.
The most frequent reasons for aneurysm repair in the
surveillance group were growth of the aneurysm in 77
(70.6%), patient anxiety and request for repair in 12
(11.0%), and the development of aneurysm-related symp-
toms in 8 (7.4%). The rate of aneurysm repair in the
surveillance group increased with increasing baseline diam-
Table I. Patient baseline characteristics
Age, mean (SD)
Male gender, n/N (%)
White race, n/N (%)
Baseline AAA size, mean (SD) cm
Hispanic ethnicity, n/N (%)
Creatinine, mean (SD) mg/dL
Tobacco use, n/N
Medication use, n/N (%)
Medical history, n/N (%)
Family history of aneurysmal disease
Congestive heart failure
Coronary artery disease
Peripheral vascular disease
Other disease history
77/295 (26.1)62/298 (20.8) .13
AAA, Abdominal aortic aneurysm; ACE, angiotensin-converting enzyme inhibitor; NA, not applicable; n/N, number of events/number at risk; SD, standard
aDerived from Pearson ?2test unless otherwise specified.
bDerived from two-sample t tests assuming unequal variances.
cFisher’s exact test.
JOURNAL OF VASCULAR SURGERY
Volume 51, Number 5
Ouriel et al 1083
eter of the aneurysm at the time of randomization. The rate
of repair was 19.6% among patients with aneurysm diame-
ters of 4.00 to 4.25 cm compared with 56.4% in patients
with aneurysms with diameters of 4.75 to 5.00 cm.
Mortality. The 30-day operative mortality rate in the
early EVAR group was 0.6% (2 of 322). There were no
deaths ?30 days of randomization in the surveillance
group. Among 109 surveilled patients who eventually un-
derwent aneurysm repair, the 30-day operative mortality
was 0.9% (1 of 109). After a mean follow-up of 20 ? 12
in the early-EVAR group was 1.01 (95% CI, 0.49-2.07,
P ? .98; Fig 3).
Rupture or aneurysm-related death. Aneurysm rup-
ture or aneurysm-related death occurred in two patients
(0.6%) in the early EVAR group and in two patients (0.6%)
in the surveillance group. One patient in the early-EVAR
group died of multisystem organ failure during the hospi-
talization for aneurysm repair, and the second died of a
fall-related intracranial hemorrhage ?30 days after a sec-
ondary procedure to treat an endoleak. One patient in the
surveillance group experienced aneurysm rupture and sur-
vived emergency EVAR. A second patient in this group
underwent EVAR and died ?30 days of the procedure.
The primary end point—time to rupture or aneurysm-
4). The unadjusted hazard ratio was 0.99 (95% CI, 0.14-
7.06, P ? .99) in the early EVAR group. There was no
evidence of nonproportional hazards between the two
groups over time; survival was similar in the two groups
early as well as later after randomization.
Other perioperative complications and secondary
procedures. Major perioperative complications in the pa-
tients who underwent aneurysm repair in the early EVAR
group (322 patients) and the surveillance group (112 pa-
tients) are listed in Table III. The most frequent complica-
tions were vascular, usually at the femoral entry site, fol-
lowed by wound infections, cardiac events, and pulmonary
complications. Endograft migration occurred in two pa-
tients through 1 year of follow-up; one was in a patient in
the early EVAR group (0.3%) and the other was in a patient
initially randomized to surveillance (1.3%). Graft limb
thrombosis occurred in 18 patients through 1 year at a
similar frequency between groups, consisting of 13 pa-
tients (4.8%) in the early EVAR group and 5 (5.8%) in
the surveillance group. Endoleaks were noted in just
?10% of patients and were most often of the type II
variety (Table IV).
There were 19 secondary procedures, including 8 pro-
cedures for graft limb occlusion, 9 for endoleak (2 for type
I and 7 for type II leaks), and 2 for graft kinks or limb
stenoses. There were 20 readmissions: 18 for secondary
endovascular procedures and 2 for conversion to open
repair after attempted endovascular graft implantation.
Two patients in the early EVAR group required open
surgical graft repair, one at 48 days after the endograft
implantation due to iliac occlusion and one at 60 days after
an unsuccessful attempted EVAR implant.
The prevalence of AAAs, a preventable cause of death,
is increasing. Rupture of an aneurysm is unpredictable,
rarely foreshowed by warning symptoms but lethal in up to
90%.10Recognition of these facts led to United States
Congressional approval in 2007 of the SAAVE act to
support ultrasound screening for aneurysms.11The risk of
decisions for an individual patient are based on weighing the
estimated risk of rupture against the estimated risk of death
from treatment. Although the balance is clearly in favor of
treating large aneurysms, there remains uncertainty for treat-
ing smaller aneurysms, and several prospective randomized
trials have been conducted to address this question.
In this study, we sought to clarify the distinction
between small and large aneurysms by defining small
aneurysms as those ?5.0 cm in diameter. Aneurysms of
this size can rupture: the United Kingdom Small Aneu-
rysm Trial (UKSAT) reported a rupture rate of approxi-
mately 1% per year.1When an AAA is detected, the
Table II. Frequency of the major end points in
surveillance and early endovascular repair treatment
Received endograft device
Rate of endograft implant
Rate of repair (open and
30-day overall mortality
Composite end point
Secondary interventions, No.
362/728 (49.7) 366/728 (50.3)
109/362 (30.1) 322/366 (88.9)
112/362 (30.9) 326/366 (89.1)
109/109 (100) 321/322 (99.7)
109/109 (100) 321/322 (99.7)
36/116 (31.0) 109/120 (90.8)
37/116 (31.9) 110/120 (91.7)
13/351 (3.7) 254/353 (72.0)
EVAR, Endovascular aneurysm repair.
aThe data are number of patients (percent).
JOURNAL OF VASCULAR SURGERY
1084 Ouriel et al
patient and the clinician must determine whether repair
or observation is indicated, a decision that is based on the
relative risk of aneurysm rupture compared with the risk
failed to detect benefit with early open surgical repair
compared with surveillance:
● The UKSAT randomly assigned 1090 patients with
4.0- to 5.5-cm aneurysms to early open surgical repair
or ultrasound surveillance. Survival after 8 years of
follow-up was 7% greater in the early surgery group, a
finding limited to that specific time point and one that
was attributed to a higher rate of smoking cessation in
the surgical group.8
Fig 2. Cumulative rate of repair of abdominal aortic aneurysm according to assignment to surveillance (dashed line)
or early endovascular aneurysm repair (EVAR, solid line).
Fig 3. Kaplan-Meier estimates show the composite end point of aneurysm-related death or aneurysm rupture
according to assignment to surveillance (dashed line) or early endovascular aneurysm repair (EVAR, solid line). The
time to the composite end point did not significantly differ between groups (P ? .99).
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