Natural history and management of abdominal aortic aneurysm

INTRODUCTION — Approximately 15,000 deaths annually in the United States are attributed to
abdominal aortic aneurysms (AAA) [1]. The established therapeutic approach to this problem has
been surgical replacement of the aneurysm with a prosthetic graft. The morbidity and mortality rates
have fallen to acceptable levels for elective cases (mortality less than 5 percent). By contrast,
mortality rates are still very high for emergency repair of a ruptured aneurysm (greater than 50
percent).

Management of the patient with an AAA will be reviewed here. The clinical features and issues
related to diagnosis and screening are discussed elsewhere. (See "Epidemiology, clinical features,
and diagnosis of abdominal aortic aneurysm" and see "Screening for abdominal aortic aneurysm").

NATURAL HISTORY — An understanding of the management of patients with an AAA requires

knowledge of the natural history of this disorder. A seminal study in 1966 demonstrated that the risk
of rupture was related to the size of the aneurysm [2]. Patients with large aneurysms (>6 cm), when
compared to those with smaller aneurysms, had a much lower rate of survival (6 versus 48 percent)
and a much higher rate of rupture (43 versus 20 percent) at five years. Virtually identical survival
differences were noted in another series [3].

These and other early studies are not thought to completely reflect the natural history. Advanced
diagnostic techniques were not widely available, and the studies included more symptomatic large
aneurysms than smaller asymptomatic aneurysms.

Risk of rupture — The likelihood that an aneurysm will rupture is influenced by number of factors,
including aneurysm diameter, rate of expansion, and gender.

Aneurysm size — Aneurysm size is one of the strongest predictors of the risk of rupture, with risk
increasing markedly at aneurysm diameters greater than 5.5 cm (show figure 1) [2-9]. A statement
from the Joint Council of the American Association for Vascular Surgery and Society for Vascular
Surgery estimated the annual rupture risk according to AAA diameter [9]:
• Zero in aneurysms less than 4.0 cm in diameter

• 0.5 to 5 percent for those 4.0 to 4.9 cm in diameter

• 3 to 15 percent for those 5.0 to 5.9 cm in diameter

• 10 to 20 percent for those 6.0 to 6.9 cm in diameter

• 20 to 40 percent for those 7.0 to 7.9 cm in diameter

• 30 to 50 percent for those ≥8.0 cm in diameter

Since it is uncommon for abdominal aortic aneurysms smaller than 5 cm to rupture, many vascular
surgeons have adopted this measurement as an indication for elective repair [10,11].
Rate of expansion — The rate of expansion may also be an important determinant of the risk of
rupture [12,13]. One study, for example, found the mean expansion rate of ruptured versus
nonruptured aneurysms was 0.82 and 0.42 cm/year, respectively [12]. Thus, a small AAA that
expands ≥0.5 cm over six months of follow-up is considered at high risk for rupture [14].
The cumulative evidence from studies that prospectively followed the size of abdominal aortic
aneurysms suggests that larger aneurysms expand about 0.3 to 0.4 cm per year [4,12,15]. This was
illustrated in an analysis from the UK Small Aneurysm trial in which the following annual growth rates
were noted [15]:
• 0.19 cm per year for aneurysms 2.8 to 3.9 cm in baseline diameter
 • 0.27 cm per year for those 4.0 to 4.5 cm in baseline diameter

• 0.35 cm per year for those 4.6 to 8.5 cm in baseline diameter

Growth tends to be more rapid in smokers, and less rapid in patients with diabetes mellitus or
peripheral vascular disease [15]. Some aneurysms, for unclear reasons, remain relatively fixed in
size for a period of time and then undergo rapid expansion.
Gender — The risk of rupture of abdominal aortic aneurysms is increased in women compared to
men. In different studies, the rate of rupture aneurysms that were 4.0 to 5.5 cm in diameter was four
times higher in women compared with men [16] and the rate of rupture of aneurysms ≥5 cm was
significantly higher in women (18 versus 12 percent) [17].
This difference may simply be a reflection of the normal diameter of the aorta being smaller in
women than men; thus, a diameter of 5.0 to 5.5 cm represents a greater degree of dilatation in
women [8,17].
Other factors — In addition to aneurysm size, the rate of expansion, and gender, other factors
increase the risk of rupture such as continued smoking, uncontrolled hypertension, and increased
wall stress [9].
Association with other cardiovascular disease — In addition to the risk of rupture, patients with
even small abdominal aortic aneurysms are more likely to have cardiovascular disease and more
likely to experience a cardiovascular event. This increase in risk was illustrated in a prospective
study in which 4734 asymptomatic subjects over the age of 65 (mean age 75 years) underwent
screening with abdominal ultrasonography: 8.8 percent had an aortic aneurysm, which was smaller
than 3.5 cm in diameter in 88 percent [18]. During a 4.5 year follow-up, patients with an aneurysm
had a higher total mortality than those without an aneurysm (relative risk 1.32), particularly if the
aneurysm was larger than 3.5 cm in diameter; cardiovascular mortality (relative risk 1.36) and
incidental cardiovascular disease (relative risk 1.57) were also increased.
SURGERY VERSUS WATCHFUL WAITING — Appropriate patient selection and timing for
aneurysm repair is based upon identifying individuals at the greatest risk of aneurysm rupture. Once
rupture occurs, emergency repair is indicated, but mortality is extremely high due to rapid
exsanguination.
For most patients with small- or medium-sized aneurysms (eg, <5 cm in diameter), the annual risk of
rupture is similar to or lower than the risk of surgery (see "Risk of rupture" above, and see "Short-
term mortality" below). Although surgery may not be warranted, such patients are at risk for
aneurysm expansion.
For asymptomatic patients with aneurysms between 3.0 and 5.5 cm in diameter, determining the
intensity of monitoring and the timing of repair can be challenging. The choice between surgery and
surveillance should take into account patient preferences and consider the following:
• Patients with small aneurysms will often die from associated illnesses before rupture
occurs (see "Association with other cardiovascular disease" above).
• For aneurysms between 4 and 5.5 cm, the likelihood of eventually requiring surgery is 60
to 65 percent at five years and 70 to 75 percent at eight years (show figure 2) [4,16,19].
• The potential benefits of early surgery must be weighed against the perioperative mortality
risk. Estimation of risk from various risk scores may be helpful. (See "Estimation of cardiac
risk prior to noncardiac surgery" and see "Management of cardiac risk for noncardiac
surgery").
Randomized trials — The question of how to manage asymptomatic medium-sized (4.0 to 5.5 cm)
aneurysms has been addressed in two randomized trials that compared open repair to imaging
surveillance [4,16,19]. A 2007 systematic review that included only these two trials concluded that
there was no significant difference in all-cause mortality at five to eight years [20].
UK Small Aneurysm trial — The UK Small Aneurysm trial randomly assigned 1090 patients (83
percent men) with an asymptomatic AAA of 4.0 to 5.5 cm in diameter to early elective surgery or
ultrasonographic surveillance every six months with surgery performed if the aneurysm size
exceeded 5.5 cm, grew more than 1 cm in a year, or became tender or symptomatic [4,16]. The two
groups had similar cardiovascular risk factors at baseline. After a mean follow up of eight years, the
following findings were noted:
• There was an initial survival disadvantage for patients undergoing early surgery because
of a 30-day operative mortality of 5.4 percent. The survival curves crossed at three years
 and, at eight years, there was a significantly lower mortality for elective surgery (43 versus
48 percent, adjusted hazard ratio 0.83, 95 percent confidence interval 0.69 to 1.0) (show
figure 3) [16]. The mean duration of survival was the same in the two groups (6.7 versus
6.5 years) as the early increase and late decrease in survival with early surgery balanced
out.
The lower mortality with surgery may have been due to beneficial changes in lifestyle, particularly
smoking cessation, which was more frequent in the surgery group.
• During follow-up of the surveillance group, the median aneurysm growth rate was 0.33 cm
per year and the mean risk of aneurysm rupture was 1.6 percent per year during the initial
follow-up period, but increased to 3.2 percent per year during the last three years of
follow-up. The risk of rupture was four times higher in women compared with men. (See
"Gender" above).
In a subsequent analysis from the UK Small Aneurysm trial, optimal surveillance intervals were
estimated to minimize the likelihood of aneurysm growth to greater than 5.5 cm between screening
visits [15]. To limit the risk of such expansion to <1 percent, ultrasonography should be performed at
intervals of 36, 24, 12, and three months for aneurysms of 3.5, 4.0, 4.5, and 5.0 cm, respectively.
ADAM trial — The United States ADAM trial consisted of 1136 patients (over 99 percent male),
aged 50 to 79 years, with an aneurysm 4.0 to 5.4 cm in diameter [19]. Patients were randomly
assigned to surgery within six weeks or surveillance with ultrasound or CT every six months; elective
surgery was performed when the aneurysm enlarged to more than 5.5 cm or became symptomatic.
Operative mortality in this trial was only 2.7 percent. After a follow-up of 4.9 years, there was no
difference in mortality between surgery and surveillance (25 versus 21.5 percent) or death related to
the aneurysm itself (3 versus 2.6 percent). Sixty-two percent of patients in the surveillance group
underwent surgery (show figure 2) and aneurysm rupture occurred in 1.9 percent (0.6 percent per
year).
Monitoring schedule — The optimal surveillance schedule for patients not treated surgically has
not been clearly defined. In the randomized trials of medium-sized aneurysms (4.0 to 5.5 cm),
abdominal ultrasonography (or CT scan) was performed at six month intervals [4,16,19]. In the report
cited above from the UK Small Aneurysm trial, optimal surveillance intervals were 36, 24, 12, and
three months for aneurysms of 3.5, 4.0, 4.5, and 5.0 cm, respectively [15]. Such a schedule should
reduce the risk of aneurysm growth to more than 5.5 cm to less than 1 percent.
Summary — The 2005 American College of Cardiology/American Heart Association (ACC/AHA),
published guidelines on the diagnosis and management of peripheral arterial disease in collaboration
with major vascular medicine, vascular surgery, and interventional radiology societies [14]. The
following recommendations were made for monitoring of patients with AAA:
• Aneurysms 4.0 to 5.4 cm in diameter should be monitored by ultrasound or CT every 6 to
12 months.
• Aneurysms 3.0 to 4.0 cm in diameter should be monitored by ultrasound every two to
three years.
The 2005 ACC/AHA guidelines recommended surgical repair of abdominal aortic aneurysms ≥5.5 cm
in diameter in asymptomatic patients [14]. This recommendation was made based upon data from
studies of predominantly men [17], and does not take into account the width of the aorta in relation to
overall body size in either men or women.
We recommend elective repair for aneurysms greater than twice the size of the non-aneurysmal
aorta (normal segment) or for those with rapid expansion, defined as growth of more than 0.5 cm
during a six month interval.
MEDICAL THERAPY — Medical therapy may be beneficial in patients with small to medium-sized
aneurysms who are not treated surgically [21].
Cessation of smoking — Smoking is a major risk factor for aneurysm formation, aneurysm growth,
and aneurysm rupture [8,22-24]. It has been estimated that continued smoking increases the rate of
aneurysm growth by 20 to 25 percent [8]. (See "Epidemiology, clinical features, and diagnosis of
abdominal aortic aneurysm", section on Smoking).
The 2005 ACC/AHA guidelines recommended that all individuals with AAA or a family history of AAA
should be advised to stop smoking and offered cessation interventions [14]. (See "Management of
smoking cessation").
Risk factor reduction — The role of treating cardiovascular risk factors, such as hypertension and
dyslipidemia, on aneurysm growth or rupture are not known. However, these modalities may prolong
survival by their effect on cardiac and cerebrovascular disease. As an example, long-term statin use
has been associated with reduced all-cause and cardiovascular mortality in patients who have
undergone previous successful surgical repair of an AAA [25]. (See "Secondary prevention of
cardiovascular disease: Risk factor reduction").
The 2005 ACC/AHA guidelines recommended that patients with AAA should have blood pressure
and lipids controlled as recommended for patients with atherosclerotic disease (ie, treated as a
coronary heart disease equivalent) [14]. (See "Secondary prevention of cardiovascular disease: Risk
factor reduction").
A preliminary retrospective study suggested that statins may also be of benefit in patients treated
medically, reducing mortality and possibly slowing aneurysm growth [26]. Suppression of aneurysm
expansion has also been noted in an experimental model in which the benefit appeared to be
mediated by antiinflammatory effects [27]. Although confirmation of the efficacy of statin therapy on
AAAs is required in humans, this does not affect practice because all patients with an AAA should be
treated with a statin for secondary prevention [14].
Beta blockers — There may be a role for pharmacologic adjunctive therapy using beta blockers,
although randomized evidence addressing this question is limited. An initial study evaluated 121
patients with an infrarenal aortic aneurysm who were monitored by serial ultrasound examination; 38
of the patients were treated with a beta blocker [12]. The mean expansion rate was significantly
lower in the patients receiving a beta blocker (0.36 versus 0.68 cm per year).
A subsequent trial randomly assigned 548 patients with a small asymptomatic abdominal aortic
aneurysm (mean diameter 3.8 cm) to placebo or propranolol [28]. At 2.5 years, the study purported
to show no benefit from propranolol therapy. However, there were two major problems with this
study. First, it may have been underpowered to detect a benefit from propranolol since propranolol
therapy was associated with nonsignificant trends toward a lesser increase in aneurysm growth rate
(0.22 versus 0.26 cm/year, p = 0.11) and elective surgery (20.3 versus 26.5 percent, p = 0.11).
Second, 42 percent of patients in the propranolol group discontinued the medication, a much higher
rate than seen in other beta blocker studies in patients with cardiovascular disease.
We and the 2005 ACC/AHA guidelines suggest beta blocker therapy in patients with an AAA who are
being followed nonoperatively [14]. Because of the possible benefit on aneurysm expansion, beta
blockers are a preferred drug for the treatment of hypertension or angina. The adequacy of beta
blockade is usually judged by the heart rate response.
Antibiotic therapy — Chlamydophila (formerly Chlamydia) pneumoniae and certain other infectious
agents have been implicated in the pathogenesis of atherosclerosis, and antibiotic therapy has been
studied for a potential beneficial effect on clinical coronary heart disease. Clinical trials have failed to
support a role for antibiotic therapy for coronary heart disease. (See "Chlamydophila (Chlamydia)
pneumoniae infection as a potential etiologic factor in atherosclerosis", section on Possible role of
antichlamydial therapy, and see "Pathogenesis of atherosclerosis", section on Infection).
Antibiotic therapy has also been evaluated for its potential effect on AAA expansion. In a trial of 92
patients with small aneurysms (mean diameter 3.75 cm), 43 were randomly assigned to treatment
with roxithromycin for 28 days while the rest received placebo; both groups were followed for 1.5
years [29]. The mean annual expansion rate of the aneurysms was reduced among patients
receiving roxithromycin compared with those receiving placebo (1.56 versus 2.75 mm per year).
More data are needed before this approach can be recommended.
SURGICAL THERAPY — Once it has been determined that the patient needs surgery, the options
for surgical repair include the traditional transabdominal route or the more recently popularized
retroperitoneal approach [10].
As the techniques for repair have become more refined, the technical complications of elective
surgery have markedly decreased.
• Acute renal failure, distal embolization, wound infection, colonic ischemia, false aneurysm
formation, aortoduodenal fistula, graft infection, and perioperative bleeding have all
become less common events during routine elective aortic surgery.
• Perioperative care has improved with the near universal availability of invasive monitoring
techniques [30].
• Autologous blood donation and cell saver use has greatly diminished the need for stored
blood transfusion, thereby decreasing the risks of allogeneic transfusions. (See
"Preoperative autologous blood donation", section on benefits).
The most common nontechnical complications of AAA repair relate to the preoperative cardiac and
pulmonary status of the patient [10,30]. Cigarette smokers with significant chronic obstructive
pulmonary disease and patients with coexistent coronary disease are more likely to experience
perioperative events such as atelectasis, pneumonia, arrhythmias, or coronary ischemia.
Preoperative evaluation — Patients with AAA are more likely to have underlying cardiovascular
disease and more likely to experience a cardiovascular event whether or not they undergo surgical
repair [18,31]. Thus, a careful preoperative assessment is mandatory in these patients in order to
minimize operative risk. A number of risk scores have been developed, with the revised Goldman
cardiac risk index being most widely used (show table 1).
The critical issues of estimating cardiac risk and the management of cardiac risk prior to noncardiac
surgery are discussed in detail separately. (See "Estimation of cardiac risk prior to noncardiac
surgery" and see "Management of cardiac risk for noncardiac surgery").
Short-term mortality — Thirty-day mortality after elective aneurysm repair was 5.8 and 2.7 percent
in the UK Small Aneurysm trial and the ADAM trial, respectively [16,19]. Perioperative mortality is
much higher with emergency surgery, occurring in 37 percent of 81 patients in a large screening trial
[32]. Most perioperative mortality and morbidity is due to cardiac events.
The short-term outcome after elective repair of an abdominal aortic aneurysm is influenced by the
volume of procedures performed at the hospital [33,34]. The magnitude of this effect was
demonstrated in a review of the Medicare database, which found that the adjusted in-hospital and
30-day mortality was inversely related to volume, ranging from 3.9 percent in hospitals performing
>79 procedures per year to 6.5 percent in those performing <17 per year [33].
The risk is also related to surgeon expertise [34]. In a nationwide review of 3912 patients in the
United States, the in-hospital mortality after abdominal aortic aneurysm repair was 2.2 percent with
vascular surgeons, 4.0 percent with cardiac surgeons, and 5.5 percent with general surgeons. The
overall mortality rate was 4.2 percent.
Poor surgical candidates — For patients who are not initially deemed to be surgical candidates,
the continued expansion of a small- or medium-sized aneurysm may be an indication to reconsider
surgery. These are sometimes difficult decisions that must include a candid discussion with patient
and family members.
The patient should be advised of the high rate of rupture of aneurysms that are ≥5.5 cm in diameter
(see "Aneurysm size" above). The magnitude of risk was assessed in a study of 198 men with
aneurysms of at least 5.5 cm in diameter for whom elective repair was not performed because of a
medical contraindication or patient refusal [35]. The one year incidence of rupture was 9.4, 10.2, and
37.5 percent for aneurysms that were 5.5 to 5.9, 6.0 to 6.9, and 7.0 cm or more in diameter,
respectively.
Such patients should, in the absence of a contraindication, be placed on a beta blocker and risk
factor reduction, and patients who smoke should discontinue smoking (see "Medical therapy"
above). In addition, endovascular stent grafts may be an option.
Endovascular stent grafts — The endoluminal placement of stent grafts is a less invasive
alternative approach for repair of an aortic aneurysm. Short-term outcomes with stent grafting may
be comparable to, if not better than, those with open repair. However, the exact role of endovascular
stent grafts remains uncertain, as there are concerns about the long-term outcome. These issues are
discussed elsewhere. (See "Stent grafts for abdominal aortic aneurysms").
INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients.
(See "Patient information: Abdominal aortic aneurysm"). We encourage you to print or e-mail this
topic review, or to refer patients to our public web site, www.uptodate.com/patients, which includes
this and other topics.
RECOMMENDATIONS — Our recommendations are in broad agreement with the 2005 ACC/AHA
guidelines [14].
Indications for aneurysm repair — The indications for aneurysm repair are largely based upon the
presence of symptoms, aneurysm size, and the rate of expansion.
• Patients with symptomatic aneurysms should undergo repair, regardless of aneurysm
diameter.
• Patients with asymptomatic aneurysms that are more than twice the size of the normal
segment should be considered for repair. (See "Surgery versus watchful waiting" above).
• Early repair may be beneficial in patients whose aneurysm increases ≥0.5 cm in diameter
in six months. (See "Rate of expansion" above).
 • Repair of suprarenal and/or thoracoabdominal aneurysms involves more extensive
surgery and greater operative risk. Repair of such aneurysms may be beneficial at
diameters >5.5 to 6.0 cm in diameter.
• AAA repair may be reasonable in patients with medium-size aneurysms who also have
iliac or femoral artery aneurysms requiring treatment, and in patients with severe
coexistent occlusive disease or thrombotic or embolic complications.
Surgical versus endovascular repair — We and the ACC/AHA guidelines recommend surgical
repair for most patients, although the use of endovascular stent grafts is an area of active
investigation and improvement. (See "Stent grafts for abdominal aortic aneurysms").
• Open surgical repair is recommended for patients at low or average risk of operative
complications.
• Endovascular repair is suggested in patients at high risk of complications from open
operations.
• Endovascular repair may be considered in patients who are not at high surgical risk, but
evidence of benefit is less well established in this setting.
Watchful waiting — For most patients with medium-sized aneurysms, regular surveillance and
medical therapy are appropriate.
• Aneurysms 4.0 to 5.4 cm in diameter should be monitored by ultrasound or CT every 6 to
12 months.
• Aneurysms 3.0 to 4.0 cm in diameter should be monitored by ultrasound every 2 to 3
years.
• Medical therapy consisting of smoking cessation and other modalities of secondary are
recommended in all patients. We suggest that beta blocker therapy also be used because
of the possible benefit on aneurysm expansion. In addition, beta blockers are a preferred
drug for the treatment of hypertension or angina. The adequacy of beta blockade is
usually judged by the heart rate response (see "Medical therapy" above).