**4. Evidence base for EVAR**

174 Aneurysm

This is the reason why there are screening studies among the target population in order to save lives and decrease health costs. The great interest is to detect and treat the AAA before

Because open surgery has non-negligible mortality and postoperative complications associated with a long hospital stay (10.8 days average) scientists tried to develop alternative

Minimally invasive techniques were developed in order to exclude the aneurysm from the circulation and to provide a new circulator channel towards the legs. Potential applications of endovascular grafts have been found in all areas of vascular surgery but their use for aortic aneurysms was the first to be explored. Endovascular aneurysm repair (EVAR) is an alternative to open surgery in the management of AAA. Juan Parodi and colleagues performed the first endovascular aneurysm repair in Argentina in 1991 [27,28]. Two decades after, the technique has evolved immensely and new devices developed allowing to a greater number of patients to be treated with EVAR. Repair of aortic abdominal aneurysm

EVAR is progressively replacing open surgery and now accounts for more than half AAA repairs [31] as for example endovascular repair of AAA in Kaiser Hawaii Hospital (USA)

A study published in November 2011 identifies the rate of endovascular treatment for AAA in different countries during 2005-2009 (**Figure 2**), whose prospective data were included in

rupture but the problem is that most of them are asymptomatic.

methods to treat this disease addressing those cases with surgical high risk.

(AAA) is performed to prevent progressive expansion and rupture. [27, 29 30]

**Figure 2.** Rate of EVAR in the management of AAA in different countries

was 50% in 2004 of the surgical activity.

In order to evaluate this new method there are registries [36] (retrospective studies) as: RETA (registry of endovascular treatment for aneurysms) in the UK, started in 1996 [37], EUROSTAR also started in 1996 [38], the Lifeline registry in the USA started in 1998 [39]. There are also randomized, controlled, multicenter trials: EVAR 1 and 2 initiated in 1999 and DREAM (Dutch randomized endovascular aneurysm management) started in 2000.

In RETA, 31 UK centers submitted data. From January 1996 to December 1998 611 cases were enrolled. Four percent received an aortic tube device, 60% an aorto-iliac device and 36% an aorto uni-iliac device with femoro-femoral crossover graft. The objectives were to assess early morbidity and mortality. Conversion to open repair was in 5% of cases. The overall mortality was 7% vs. 12% for open surgery. Endoleaks were more common in larger aneurysms (2% if aneurysm diameter was < 6 cm and 10% if it was > 6 cm) [37].

EUROSTAR (European collaboration on stent graft techniques for aortic aneurysm repair) Registry was established in 1996. The results were published in JVS in October 2000, 88 European centers have contributed, enrolling 2464 patients with a main follow up of 12.19 months. The 30 days mortality was 3.1%. The cumulative risk of late conversion was 2.1%/year and of rupture 1%/year. The significant factors for rupture were: type I endoleak, type III endoleak, graft migration and postoperative kinking of the endograft. The feasibility rate of the procedure was 97% of patients using first and second generation devices. The rate of late failure of the devices was 3%/year.[38,40]

The Lifeline registry was established in 1998 in the USA and the results were published in JVS in July 2005. The end point was to evaluate the long-term outcome of patients treated with EVAR using 5 devices who had FDA approval (Guidant Ancure, Medtronic AneuRx, Gore Excluder, Endologix PowerLink, Cook Zenith). It enrolled 2664 patients with EVAR vs. 334 open repair control patients. The 30 day mortality of EVAR was 1.7% which was not different from surgical control (1.4%), this in spite of the EVAR patients who were significantly older and sicker (more comorbidities). The risk of rupture of the aneurysm after EVAR was 3 times higher (2.1%) in women than in men (0.7%). The risk of rupture of the AAA remained stable over a 6 year period at a level of 1%/year. The surgical conversion rate was 3% at a year and 5% at 6 years (low). All this shows that EVAR is safe and effective in preventing aneurysm rupture and avoiding AAA related death. [39]

The most known and discussed randomized, controlled, multicentre trials are the UK EVAR1 and 2 which were initiated in 1999 and published in "The Lancet" in 2004 [41] and 2005 [42]. EVAR 1 compares endovascular procedures vs. open repair. A great number of patients (2068) were enrolled, aged over 60 years with a non ruptured AAA and who had an aneurysm of more than 5.5 cm in CT scan diameter. Morphological suitability for EVAR [43] and choice of the stent graft was decided by each center (41 centers enrolled). The 30-day mortality rate was 1.7% compared with 4.7% for open surgery. The secondary interventions were 9.8 for EVAR and 5.8 for open repair. Patients unfit for open repair because of significant comorbidities were randomized for EVAR or best medical treatment in the EVAR 2 trial. 338 patients aged 60 years or older with an AAA >5.5 cm in diameter were enrolled. The primary end point was aneurysm related mortality, postoperative complications and hospital costs. The risk of rupture is 25%/year for aneurysms with diameters greater than 6 cm. The 30-day mortality was 9% in EVAR group and in the non intervention group was 9.0 / 100 pers / year. There was no significant difference between the EVAR group and non intervention group for all cause mortality.

The DREAM trial initiated in 2000 enrolled 345 patients considered suitable for both types of treatment. The 30-day mortality after EVAR was 1.2% compared with 4.6% for open surgery. The results were published in 2002 in Journal of Cardiovascular Surgery [44, 45].

The Veteran open vs. endovascular repair (OVER) trial started enrollment in October 2002 in the US. It was design to enroll 5 years followed by a 4 year follow up. In total a 9 years survey. The primary outcome is long-term survival and secondary outcomes included morbidity, procedure failures and need for secondary procedures and costs. 33 centers are participating, 684 patients were enrolled in September 2006 and the investigators expect 900 by the end of the study. Patients enrolled had aneurysms of more than 5cm and were candidates for both procedural types. [46]

The French trial *"Anevrisme Chirurgie vs Endoprothese"* (ACE) also had the same enrollment conditions and primary and secondary end points.

In OVER and ACE trials were used newer devices for treating AAA than those used in EVAR 1 and DREAM (procedures performed between 1999-2003)[46]. The Gore Excluder and Medtronic AneuRx represent 2/3 from the devices used in OVER compared with only 11% used in EVAR 1.

Speaking about costs the shorter ITU and hospital stay in the EVAR group, with initial comparable costs, the cost per patient over 4 years is higher in EVAR because the cost of the endograft and subsequent of secondary interventions **(Figure 3)**[43]**.** 

In summary, EVAR has lower perioperative mortality but there is no difference in long term overall mortality. This procedure is associated with 10% risk of aneurysm related complications/ year, but they can be solved by further endovascular reinterventions [43].

EVAR is a safe, effective and durable treatment for infrarenal aortic aneurysms with suitable anatomy.

**Figure 3.** EVAR costs per patient ( modified after [43])

intervention group for all cause mortality.

candidates for both procedural types. [46]

11% used in EVAR 1.

anatomy.

conditions and primary and secondary end points.

The most known and discussed randomized, controlled, multicentre trials are the UK EVAR1 and 2 which were initiated in 1999 and published in "The Lancet" in 2004 [41] and 2005 [42]. EVAR 1 compares endovascular procedures vs. open repair. A great number of patients (2068) were enrolled, aged over 60 years with a non ruptured AAA and who had an aneurysm of more than 5.5 cm in CT scan diameter. Morphological suitability for EVAR [43] and choice of the stent graft was decided by each center (41 centers enrolled). The 30-day mortality rate was 1.7% compared with 4.7% for open surgery. The secondary interventions were 9.8 for EVAR and 5.8 for open repair. Patients unfit for open repair because of significant comorbidities were randomized for EVAR or best medical treatment in the EVAR 2 trial. 338 patients aged 60 years or older with an AAA >5.5 cm in diameter were enrolled. The primary end point was aneurysm related mortality, postoperative complications and hospital costs. The risk of rupture is 25%/year for aneurysms with diameters greater than 6 cm. The 30-day mortality was 9% in EVAR group and in the non intervention group was 9.0 / 100 pers / year. There was no significant difference between the EVAR group and non

The DREAM trial initiated in 2000 enrolled 345 patients considered suitable for both types of treatment. The 30-day mortality after EVAR was 1.2% compared with 4.6% for open surgery. The results were published in 2002 in Journal of Cardiovascular Surgery [44, 45].

The Veteran open vs. endovascular repair (OVER) trial started enrollment in October 2002 in the US. It was design to enroll 5 years followed by a 4 year follow up. In total a 9 years survey. The primary outcome is long-term survival and secondary outcomes included morbidity, procedure failures and need for secondary procedures and costs. 33 centers are participating, 684 patients were enrolled in September 2006 and the investigators expect 900 by the end of the study. Patients enrolled had aneurysms of more than 5cm and were

The French trial *"Anevrisme Chirurgie vs Endoprothese"* (ACE) also had the same enrollment

In OVER and ACE trials were used newer devices for treating AAA than those used in EVAR 1 and DREAM (procedures performed between 1999-2003)[46]. The Gore Excluder and Medtronic AneuRx represent 2/3 from the devices used in OVER compared with only

Speaking about costs the shorter ITU and hospital stay in the EVAR group, with initial comparable costs, the cost per patient over 4 years is higher in EVAR because the cost of the

In summary, EVAR has lower perioperative mortality but there is no difference in long term overall mortality. This procedure is associated with 10% risk of aneurysm related complications/ year, but they can be solved by further endovascular reinterventions [43].

EVAR is a safe, effective and durable treatment for infrarenal aortic aneurysms with suitable

endograft and subsequent of secondary interventions **(Figure 3)**[43]**.** 

## **5. Indications and anatomical suitability**

Patient selection is an important element of successful EVAR. We should carefully investigate and consider the anatomy of the abdominal aorta, the relationship with the emergence of the renal arteries, the calibre, tortuosity and calcifications of the iliac arteries. The misevaluation of morphological aspects can lead to immediate or late failure of the procedure. With the refinement of medical devices (multislice CT scan with 3D reconstruction, substraction angiography, sophisticated computer data analysis), we can detect all the morphological modifications in the aneurismal area in segments immediately adjacent.

The Clinical Practice Guidelines of the European Society for Vascular Surgery on the management of AAA, published in April 2011, sets out a series of recommendations in all aspects of diagnosis and management strategies of AAA (Figure 4,5) [47].

There is a consensus that in the case of small aneurysms, with a diameter between 3.0-3.9 cm, the risk of rupture in negligible. Therefore, these aneurysms do not require surgery, supervision by Doppler Ultrasound at regular intervals being sufficient. The management of the AAA with a diameter between 4.0 – 5.5 was determined by two multicenter, randomised, controlled studies, that compared the natural evolution of these aneurysms versus early intervention: UK Small Aneurysm Trial (UKSAT) and American Aneurysm Detection and Management Study (ADAM) respectively [48, 49] and a smaller study, that compared endovascular treatment versus surveillance, the CAESAR study [50]. The PIVOTAL study including aneurysms with diameters between 4.0- 5.0 cm compared the endovascular treatment versus Doppler Ultrasound surveillance [51].

Medium-term results of these studies did not indicate a statistically significant difference in terms of overall mortality at 5 years, the results being similar in the long-term, at 12 years

**Figure 4.** Management strategy of AAA according to the size of the aneurysm (modified after [47])

**Figure 5.** Management of large aneurysms, with a diameter ≥5,5 cm (modified after [47])

[48, 52]. The rupture rate of the aneurysms was 1% in the surveillance group and the overall mortality rate was 5,6% in the early intervention group.

178 Aneurysm

**Figure 4.** Management strategy of AAA according to the size of the aneurysm (modified after [47])

**Figure 5.** Management of large aneurysms, with a diameter ≥5,5 cm (modified after [47])

The results of the above mentioned large studies, UKSAT and ADAM were recently included in the COCHRANE study, that underlines the safety and through this the benefits of the Doppler ultrasound surveillance of the AAA with a diameter between 4.0 and 5.5 cm [53].

Performing Doppler Ultrasound surveillance of small aneurysms (4.0-5.5 cm) is safe and recommended for asymptomatic aneurysms. If the aneurysm reaches the 5.5 cm diameter limit, measured by Doppler ultrasound (in male patients), it becomes symptomatic or there is an annual diameter increase of >1cm/year, the patient must be immediately referred for further investigation to the specialised vascular surgery department.

As highlighted, the diameter of the AAA establishes the moment for intervention, but this criteria alone is not enough to establish the indication for the endovascular treatment of the AAA. With new treatment methods new complications occur, requiring further investigations in order to assess the feasibility of the AAA for EVAR. The morphological criteria of the AAA are the ones that can establish or exclude the indication of EVAR. The failure to comply with these criteria, requested also in the instruction manuals of the endoprostheses currently on the market may lead to the increase of the peri- and postoperative complication, reintervention and post-EVAR mortality rate.

An average 34% of AAA is not eligible for EVAR, most of them because of an adverse morphology. [54]

The universal classification system defines the aneurysm in relation with the origin of renal arteries:


Another classification employed for EUROSTAR and DREAM trials is shown in **figure 6,**  taking into account the distance from the renals and the bifurcation of the aorta as well as the involvement of iliac arteries (the common iliac artery, arriving or not to the bifurcation of iliac arteries, occlusion or stenosis of the common iliac arteries).

The French system proposed by Kieffer & Chiche (2005) is also based on the distal extension of the aneurysm and is comparable with the EUROSTAR classification (Type I-V).

The proximal neck is by far one of the most important anatomic finding in planning an endovascular procedure. It can be classified as shown in **figure 7.** 

The diameter of the neck, its length, shape and angulation are to be considered. Aortic neck angulation is defined as the angle between the axes of the proximal infrarenal aorta and the longitudinal axis of the aneurysm. It is classified as: mild < 40 degrees, moderate < 60dgr, and severe > 60dgr.

**Figure 6.** Classification of AAA (modified after [40])

**Figure 7.** Morphology of the aortic neck (modified after [40])

**Figure 8.** Preoperative measurements (EUROSTAR)

The neck is the place where the endoprotheses are fixed and sealed. Seal is the apposition of the outer surface of the endograft to the luminal surface of the aorta in order to exclude the aneurysm sac from the systemic pressure. Fixation is the counterforce that prevents migration and helps to maintain seal.

Concerning the iliac arteries, the landing zone of the majority of grafts, we are interested in patency and diameter, length of the common iliac artery, shape or aneurismal, angulation or tortuosity and calcifications.

**Figure 8** shows a preoperative scheme for planning an endovascular repair showing all the anatomical features discussed above.(after [40])
