Annually, in the US approximately 15,000 deaths are caused by a rupture of an abdominal aortic aneurysm (AAA), making it the 13th leading cause of death. AAA is often referred to as ‘the silent killer’ and is estimated to affect 2.7 million Americans, half of whom are not correctly diagnosed.1 If left untreated, the risk of rupture is 80–90% through progressive thinning of the aortic vessel, which presents a serious clinical problem.2
The prevalence of AAAs in men is four times higher than that in women.3–5 Smoking is also strongly correlated with the development of AAA, and in one study 51.6% of men currently smoking had one or more AAA.5 Other recognized risk factors include a family history of AAA, hypertension, raised cholesterol, and cerebrovascular and coronary heart disease.6 The predominant risk factor for the rupture of an AAA is the diameter of the aneurysm.7 The risk of rupture increases significantly for AAAs larger than 5.5cm in diameter. Hence, universally, 5.5cm is the minimum size of aneurysm to be considered for surgical intervention.8
To reduce the number of undiagnosed cases, the Society of Vascular Surgery (SVS) and the Society for Vascular Medicine and Biology (SVMB) have both recommended the implementation of a screening program for all men 60–85 years of age, women 60–85 years of age with cardiovascular risk factors, and everybody over 50 years of age who has a family history of AAA.9 Screening for AAA is inexpensive and can be performed by checking for palpitations or using ultrasound (u/s).
Current Standards of Care
There is debate over the best method of clinically managing AAAs successfully. Open surgery has been the most popular prevention for AAA rupture; however, there is a considerable morbidity and mortality rate for standard open surgery, particularly in patients with comorbid conditions.10–15 Endovascular aneurysm repair (EVAR) therefore represents a more promising alternative for surgery in high-risk patients. EVAR is performed through small incisions, or percutaneously via the femoral arteries where a stent is fed over a guidewire to the desired position in the abdominal aorta.
In 1996, two independent voluntary registries were set up to monitor the implementation and development of EVAR.16,17 The UK Registry for the Endovascular Treatment of Aneurysms (RETA) reported a 30-day mortality rate of 7% for patients undergoing EVAR for both aortic tube and bi-iliac devices and aorto-uni-iliac devices.16 The second registry, the European Stentgraft Treatment of Abdominal Aortic Aneurysms Registry (EUROSTAR), found a mortality rate of 3.2%; however, this survey did not include results from the use of aorto-uni-iliac devices.18 The highest frequency of deaths in both registries was seen in patients who were unfit for open surgery, which suggested that EVAR presented a risk in this population.
As a follow-up to these studies, the EVAR 1 trial was started in 1999 in the UK involving 13 eligible hospitals.19 AAA patients who had aneurysms of at least 5.5cm and who were eligible for both open surgery and EVAR were enrolled. Patients were randomized to receive either open surgery or EVAR. Preliminary results reported a 1.6% death rate in the 30-day post-operative period in the EVAR group compared with 4.6% in the open surgery group. Mid-term results demonstrated a 3% mortality improvement of EVAR over open surgery after four post-operative years.19 However, after four years 41% of post-EVAR patients presented with at least one complication, in contrast to 9% in the open surgery group. In addition, in the EVAR group 20% of patients had at least one re-intervention in comparison with 6% in the open surgery group. Despite the increase in complications and re-interventions in the EVAR group, no difference was noted in the quality of life between the two groups. Long-term results from this trial will evaluate the cost-effectiveness of EVAR in AAA patients.
A second EVAR trial—EVAR 2—hypothesized that EVAR compared with no intervention would reduce mortality and improve quality of life in patients unfit for surgery with aneurysms over 5.5cm in diameter.20 The trial included patients in significantly worse health than those in EVAR 1 who were considered high-risk. All patients were followed for one year: within this time approximately 45% of patients treated with EVAR died, in comparison with a 40% mortality rate in the no intervention group. The mortality rate for EVAR patients in EVAR 2 was much higher than that seen in EVAR 1, suggesting that EVAR is not a safe procedure in high-risk patients.20 The study group is continuing to monitor patients until 2010, which should indicate any alterations in the long term between the two groups.
The Dutch Randomised Endovascular Aneurysm Management (DREAM) trial follows a similar protocol to EVAR 1.21 The DREAM trial was a short-term randomized prospective trial with the main focus of comparing the quality of life during the first post-operative year between elective EVAR and open surgery.21 Early in the post-operative period a significant improvement in quality of life was noted in the EVAR-treated group. The authors of the study concluded that on the basis of the overall results, endovascular repair is preferable to open repair in patients with an AAA at least 5cm in diameter, although long-term follow-up would be needed to determine whether this advantage is sustained. A subsequent follow-up analysis of the same randomized participants investigated two-year survival rates and moderate to severe complications of EVAR compared with open surgery.22 The cumulative survival rates for open surgery and EVAR were 89.6 and 89.7%, respectively. The survival rates free of moderate to severe complications were also similar over two years: 65.9% for open repair and 65.6% for EVAR.
Wilt et al. compared open surgery with EVAR through the use of randomized controlled trials of EVAR and open surgery, systematic reviews, surveillance programs, non-randomized US trials, and clinical registries.23 The report concluded that EVAR of aneurysms larger than 5.5cm in diameter does not improve long-term survival or quality of life compared with open surgery. In addition, EVAR was not found to improve survival rate in patients unfit for open surgical repair. The study advised that US randomized trials should be conducted that evaluate currently approved devices and the need for re-intervention and long-term surveillance.
The Evolution of Endovascular Aneurysm Repair
While previous studies evaluating the benefits of EVAR in AAA have produced conflicting evidence, it must be noted that many of these studies utilized first-generation stent technology. Studies have generally been conducted using all devices available at that time; therefore, comparisons between endografts have been difficult, although a small collection of studies have set out to evaluate potential differences between the devices. Moreover, during the past 10 years the endovascular stent grafts used in EVAR have been vastly improved and modified to become more flexible and smaller in diameter. Several devices have received approval from the US Food and Drug Administration (FDA), including the Gore Excluder (WL Gore and Associates, Inc., Flagstaff, AZ), AneuRx (Medtronic, Santa Rosa, CA), Zenith (Cook Inc., Bloomington, IN), and PowerLink (Endologix, Irvine, CA).
The Lifeline Registry for aneurysm repair was established in the US in October 1998 to evaluate the long-term results of endovascular repair of AAA with FDA-approved devices. The registry contained data on 2,664 EVAR patients and 334 open surgical control patients. There was no significant difference in operative mortality or freedom from aneurysm-related death after five years of follow-up. Freedom from secondary intervention in the EVAR group was 84% at one year and 78% at five years. Most of the secondary interventions (85%) were performed ≤30 days after EVAR.
Over a seven-year period, an evaluation was performed on mid- and long-term device migration between the AneuRx and Zenith endografts in 130 patients after aneurysm repair.24 Using a threshold of 5mm of movement after four post-operative years, 67% of AneuRx and 90.1% of Zenith patients remained migration-free. The difference in migration between the devices was thought to be due to fixation methods to the artery. The Zenith device had additional hooks and barbs, which prevented migration. The authors concluded that choice of device and aortic neck length both affected migration, and that long-term surveillance is required after EVAR.
The third-generation Gore Excluder is the lowest profile bifuricated stent graft approved for use in the US and has proximal fixation barbs. The EUROSTAR database collected experience on the Excluder device in large and small aneurysms over a six-year period.25 The device had an improved rate of endoleak, device migration, and primary conversion into open repair in comparison with previously used devices.26 The frequency of device leaks decreased from 12% in previous EUROSTAR studies, which used older devices, to 6% using the third-generation endograft.27 Neither device migration nor aneurysm growth was affected by the size of the aneurysm.
In the US, 19 centers were involved in an elective phase II clinical trial evaluating the safety and efficacy of the Excluder endoprothesis.28 The trial noted shorter length of stay, fewer blood transfusions, and a reduction in adverse effects in patients treated with the Excluder device in comparison with open-repair patients. Five-year follow-up data have now been published on approximately one-third of this group of patients.29 Aneurysm survival rate in the Excluder group was 97% compared with 96% in the open-surgery patients, which was not statistically significant. There was a 3% frequency of endoleaks and a 38% aneurysm growth in the Excluder patients.
Haider et al.30 have recently reported on their 12-month comparison between the original Excluder and the low-permeability device related to sac behavior after EVAR. Their findings indicate that the low-permeability Excluder offers greater sac shrinkage and no evidence of sac enlargement, most likely related to the lower permeability of the new graft material. The authors stated that a new version of the Excluder device is currently being evaluated to eliminate the rate of aneurysm growth.
Recently, a multicenter phase II clinical trial evaluated outcomes of the updated Excluder device for aneurysm treatment and compared the data with previously published results of the first- and second-generation Excluder devices.31 No significant difference was noted in the frequency of major adverse events or the number of endoleaks between the two devices within 30 post-operative days. However, from 14 to 24 months there was a 4% reduction reported in re-intervention with the newer device and significantly fewer major adverse events. Endovascular repair with the new device therefore reduces the need for re-intervention and maintains mid-term survival rates and rupture-free outcomes.
In a retrospective review of long-term outcomes of EVAR between 1994 and 2005, eight commercially available devices were used.32 A significant improvement in EVAR treatment was noted with current-generation stent grafts over the older devices. The report stated that endovascular repair with contemporary endografts is a safe, effective, and durable treatment for the prevention of AAA rupture and aneurysm-related death.
More recently, Ruppert et al.33 have reported on risk-adapted outcomes after EVAR. Their analysis compared different types of anesthesia from the EUROSTAR registry with the outcomes after EVAR. Their study revealed that the procedure time, the intensive care unit stay, and the hospital stay were significantly shorter for patients receiving local anesthesia than those receiving regional or general anesthesia. The systemic complications were 9% in the high-risk patients with local anesthesia, 19.7% in those with regional anesthesia, and 18.3% in those with general anesthesia (p<0.0001). Access site complications were also lower in the group with local anesthesia (4.8%) than for patients with regional anesthesia (5.4%) or patients with general anesthesia (8.3%) (p=0.0012). Early death was also significantly lower for patients with local anesthesia (0) than for those with regional anesthesia (3%) or general anesthesia (4.3%; p=0.028).
Surveillance of Patients Post-endovascular Aneurysm Repair
EVAR has been associated with potential late-onset complications including endoleaks, device migration, kinking/fracture, and limb outflow impairment; therefore, lifetime surveillance of EVAR patients has been made necessary.34 Computed tomography (CT) scanning is currently the most widely used surveillance measure for post-EVAR patients.35 CT scanning involves a triphasic protocol that exposes the patient to a dose of radiation equivalent to 300–400 X-rays, which has been associated with a lifetime risk of fatal cancer affecting one in 2,000 patients.36 It has been suggested that a biphasic CT protocol should be used to reduce the radiation burden; however, this reduces the reliability of detecting slow-flow endoleaks.37–39 In addition, contrast media used in CT scanning have been linked to anaphylactic reactions that can be nephrotoxic, limiting the use of CT scans in the elderly population with renal impairment. The majority of AAA patients are elderly and often present with mild to moderate renal impairment; therefore, there is need for a new method of surveillance.
Magnetic resonance imaging (MRI) has been reported to allow accurate detection of complications post-EVAR; however, it is extremely costly and cannot be used successfully in patients with pacemakers and stainless steel stent grafts. Duplex u/s (Dus) has recently become more popular in post- EVAR patients, although Dus has its own disadvantages: it is operator-dependent, it is less effective in overweight individuals, and bowel gas can interfere with the readings.
The use of Dus in post-EVAR patients has resulted in mixed success.40–44 A study conducted in 1999 compared the sensitivity of complex enhanced duplex with arterial phase CT, and concluded that Dus was very sensitive and was able to detect more endoleaks than those identified by the CT scan.44 However, endoleaks that were not detected by CT scanning were questionable. A later study by the same group compared enhanced contrast Dus with biphasic CT scanning and found that CT outperformed Dus considerably.45 In contrast, a comparison between enhanced contrast Dus and biphasic CT scanning reported that Dus was comparable to CT scans and concluded that it should be implemented into the surveillance of post- EVAR patients.40
Endosensors are now being developed for use in AAA patients after endovascular repair. The CardioMEMS endosensor (CardioMEMS, Inc., Atlanta) is able to monitor pressure changes inside the aneurysm and transmit measurements wirelessly through radiowaves to a recording device held over the patient’s body. The safety of this device has not yet been established in the long-term monitoring of post-EVAR patients. Other endosensors are currently being developed that use u/s waves to generate an image of the aneurysm.
Summary and Conclusion
Traditionally, open surgery has been used to treat AAA; however, the mortality rate of this technique is 50%. EVAR has been demonstrated in several trials to be a successful alternative to open surgery and offers improvement in hospitalization time, survival rates, and adverse effects. As the technology has evolved, promising clinical results have been reported indicating that the more contemporary designs with either barbs or hooks for fixation reduce device migration. The use of a percutaneous approach and local anesthesia has further reduced the procedural complications, offering patients with EVAR earlier discharge from hospital and quicker return to a normal lifestyle. Future efforts should focus on further improving the durability of the devices and assuring that we have good long-term results. Another important aspect that we have to look into is improving surveillance of AAA patients. The potential use of endosensors placed at the time of the procedure could identify those patients who have potential problems such as endoleak or endotension. Combined with less invasive procedures it could lower costs on a long-term basis, and also reduce the need for more invasive surveillance measures.