Endovascular repair of abdominal aortic aneurysm

Sharath Chandra Vikram Paravastu; Rubaraj Jayarajasingam; Rachel Cottam; Simon J Palfreyman; Jonathan A Michaels; Steven M Thomas

doi:10.1002/14651858.CD004178.pub2

. 2014 Jan 23;2014(1):CD004178. doi: 10.1002/14651858.CD004178.pub2

Endovascular repair of abdominal aortic aneurysm

Sharath Chandra Vikram Paravastu ¹, Rubaraj Jayarajasingam ², Rachel Cottam ³, Simon J Palfreyman ⁴, Jonathan A Michaels ⁵, Steven M Thomas ^6,^✉

Editor: Cochrane Vascular Group

PMCID: PMC10749584 PMID: 24453068

Abstract

Background

An abnormal dilatation of the abdominal aorta is referred to as an abdominal aortic aneurysm (AAA). Due to the risk of rupture, surgical repair is offered electively to individuals with aneurysms greater than 5.5 cm in size. Traditionally, conventional open surgical repair (OSR) was considered the first choice approach. However, over the past two decades endovascular aneurysm repair (EVAR) has gained popularity as a treatment option. This article intends to review the role of EVAR in the management of elective AAA.

Objectives

To assess the effectiveness of EVAR versus conventional OSR in individuals with AAA considered fit for surgery, and EVAR versus best medical care in those considered unfit for surgery. This was determined by the effect on short, intermediate and long‐term mortality, endograft related complications, re‐intervention rates and major complications.

Search methods

The Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator (TSC) searched the Specialised Register (January 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12). The TSC also searched trial databases for details of ongoing or unpublished studies.

Selection criteria

Prospective randomised controlled trials (RCTs) comparing EVAR with OSR in individuals with AAA considered fit for surgery. and comparing EVAR with best medical care in individuals considered unfit for surgery. We excluded studies with inadequate data or using an inadequate randomisation technique.

Data collection and analysis

Three reviewers independently evaluated trials for appropriateness for inclusion and extracted data using pro forma designed by the Cochrane PVD Group. We assessed the quality of trials using The Cochrane Collaboration's 'Risk of bias' tool. We entered collected data in to Review Manager (version 5.2.3) for analysis. Where direct comparisons could be made, we determined odds ratios (OR). We tested studies for heterogeneity and, when present, we used a random‐effects model; otherwise we used a fixed‐effect model. We tabulated data that could not be collated.

Main results

Four high‐quality trials comparing EVAR with OSR (n = 2790) and one high‐quality trial comparing EVAR with no intervention (n = 404) fulfilled the inclusion criteria. In individuals considered fit for surgery, a pooled analysis, including 1362 individuals randomised to EVAR and 1361 randomised to OSR, found short‐term mortality (including 30‐day or inhospital mortality, excluding deaths prior to intervention) with EVAR to be significantly lower than with OSR (1.4% versus 4.2%, OR 0.33, 95% confidence interval (CI) 0.20 to 0.55; P < 0.0001). Using intention‐to‐treat analysis (ITT) there was no significant difference in mortality at intermediate follow‐up (up to four years from randomisation), with 221 (15.8%) and 237 (17%) deaths in the EVAR (n = 1393) and OSR (n = 1390) groups, respectively (OR 0.92, 95% CI 0.75 to 1.12; P = 0.40). There was also no significant difference in long‐term mortality (beyond four years), with 464 (37.3%) deaths in the EVAR and 470 (37.8%) deaths in the OSR group (OR 0.98, 95% CI 0.83 to 1.15; P = 0.78). Similarly, there was no significant difference in aneurysm‐related mortality between groups, either at the intermediate‐ or long‐term follow up.

Studies showed that both EVAR and OSR were associated with similar incidences of cardiac deaths (OR 1.14, 95% CI 0.86 to 1.52; P = 0.36) and fatal stroke rate (OR 0.81, 95% CI 0.42 to 1.55; P = 0.52). The long‐term reintervention rate was significantly higher in the EVAR group than in the OSR group (OR 1.98, 95% CI 1.12 to 3.51; P = 0.02; I² = 85%). Results of the reintervention analysis should be interpreted with caution due to significant heterogeneity. Operative complications, health‐related quality of life and sexual dysfunction were generally comparable between the EVAR and OSR groups. However, there was a slightly higher incidence of pulmonary complications in the OSR group compared with the EVAR group (OR 0.36, 95% CI 0.17 to 0.75; P = 0.006).

In individuals considered unfit for conventional OSR, the one included trial found no difference between the EVAR and no‐intervention groups with regard to all‐cause mortality at final follow up, with 21.0 deaths per 100 person‐years in the EVAR group and 22.1 deaths per 100 person years in the no‐intervention group (adjusted hazard ratio (HR) with EVAR 0.99, 95% CI 0.78 to 1.27; P = 0.97). Aneurysm‐related deaths were, however, significantly higher in the no‐intervention group than in the EVAR group (adjusted HR 0.53, 95% CI 0.32 to 0.89; P = 0.02). There was no difference in myocardial events (HR 1.07, 95% CI 0.60 to 1.91) between the groups in this study.

Authors' conclusions

In individuals considered fit for conventional surgery, EVAR was associated with lower short‐term mortality than OSR. However, this benefit from EVAR did not persist at the intermediate‐ and long‐term follow ups. Individuals undergoing EVAR had a higher reintervention rate than those undergoing OSR. Most of the reinterventions undertaken following EVAR, however, were catheter‐based interventions associated with low mortality. Operative complications, health‐related quality of life and sexual dysfunction were generally comparable between EVAR and OSR. However, there was a slightly higher incidence of pulmonary complications in the OSR group than in the EVAR group.

In individuals considered unfit for open surgery, the results of a single trial found no overall short‐ or long‐term benefits of EVAR over no intervention with regard to all‐cause mortality, but individuals may differ and individual preferences should always be taken into account.

Plain language summary

Endovascular repair of abdominal aortic aneurysm

The abdominal aorta is a major blood vessel in the body that carries blood from the heart to the major organs in the chest and abdomen. An abdominal aortic aneurysm (AAA) is a balloon‐like bulge (dilation) of the aorta that is greater than 3 cm in diameter. If an AAA ruptures (bursts), this is often fatal. Hence, AAAs that are larger than 5.5 cm are usually treated surgically in order to try to prevent such a rupture. Traditionally, AAAs are treated using an open surgical repair (OSR) technique, in which the abdomen is cut open (referred to as open surgery) and the dilated aorta is repaired using fabric graft material. However, over the past 20 years, a newer, 'key hole' technique has been used, in which the AAA is repaired without the need for open surgery ‐ a thin tube is passed via the blood vessels in the groin to the site of the AAA. Once in the correct position, a sheath is introduced that acts to reline the dilated aorta, acting as an artifical blood vessel through which blood can continue to flow, bypassing the aneurysm. Hence, the risk of further expansion or rupture of the AAA is reduced, This technique is referred to as endovascular aneurysm repair (EVAR). As EVAR is a less invasive technique than OSR, in that there is no need for open surgery, it may have advantages over OSR. In addition, some individuals with other medical illnesses, for whom open surgery may be considered a high‐risk procedure and who are not fit for OSR, can be offered EVAR instead.

The review authors identified four randomised controlled trials (RCTs) of good quality that compared OSR with EVAR, involving a combined total of 2790 participants considered fit for surgery, and one RCT of good quality that compared EVAR with no intervention, involving a total of 404 participants considered unfit for OSR.

The pooled analysis of the four trials comparing OSR with EVAR showed that the death rates within 30 days of operation or during admission for surgery were significantly lower in individuals undergoing EVAR than in those undergoing OSR (1.4% versus 4.2%). However, there was no difference in death rates between the groups up to four years after the operation (intermediate follow up) or beyond four years (long‐term follow up). Participants undergoing EVAR had a significantly higher incidence of a need for an additional intervention to deal with any complications of the procedure undertaken compared with those receiving OSR. Operative complications, health‐related quality of life and sexual dysfunction were generally comparable between the two procedures. However, there was a slightly higher incidence of lung complications in the OSR group than in the EVAR group. The results of the one RCT comparing EVAR with no intervention in individuals considered unfit for OSR showed no difference in overall death rates and complication rates between the groups.

Background

Description of the condition

When the main artery in the body, the aorta, develops a balloon‐like bulge, an abdominal aortic aneurysm (AAA) is said to have developed. The prevalence of AAA (where the aortic diameter exceeds 3 cm) in the UK has been estimated at between 1.2% and 7.6% in populations over 50 years of age, depending on the criteria used to define the AAA (Khoo 1994; Scott 1995). As with most vascular diseases, the prevalence of AAA increases with age and occurs much more frequently in men than in women. In England, treatment of AAA accounts for approximately 3650 elective surgical procedures and 1100 emergency surgical procedures per year (Holt 2009).

Untreated AAAs are likely to increase in size and may eventually rupture, which can lead to death. The decision to repair an AAA is made on an individual basis, balancing the risk of treatment against the risk of aneurysm rupture. There is good evidence that the risk of rupture is related to aneurysm size; hence, whether treatment is necessary or not is generally based on the size of the AAA or the presence of symptoms.

Description of the intervention

Conventional surgical repair of AAA has been practiced since the early 1950s and involves the surgical insertion of a prosthetic (i.e. man‐made) graft. This operation is referred to as open surgical repair (OSR) as it involves a large abdominal incision, and is associated with a significant risk of complications even when individuals are otherwise fit and well. The UK Small Aneurysm Trial found that aneurysms less than 5.5 cm in diameter can be kept under observation using periodic ultrasound scanning, reserving surgical intervention for those that become larger than 5.5 cm or that produce symptoms (UKSAT 1998). The 30‐day mortality associated with surgical repair of AAA in the UK Small Aneurysm Trial was 5.8%, and reported rates range from 2% to 7% in otherwise fit individuals (Feinglass 1995; Mutirangura 1989; Olsen 1991; Steyerberg 1995; Takolander 1998; Zarins 1997). However, if rupture occurs, mortality rises steeply. Inhospital mortality rates are reported to range from 40% to 80%, but as many cases do not reach hospital it is estimated that overall mortality is higher and may reach 95% (Bengtsson 1993; Budd 1989; Campbell 1986; Eskandari 1998; Ingoldby 1986; Johansson 1986; Kantonen 1999; Thomas 1988).

In individuals who have severe coexistent cardiac, respiratory or renal disease, conventional surgical treatment may be considered too dangerous, and individuals considered unfit for surgery may not be offered OSR. In such cases, attempts may be made to lower the risk of rupture by reducing blood pressure or via other pharmacological manipulations, though there is no strong trial evidence that this is effective (Gadowski 1994; Leach 1988; Walton 1999).

The traditional approach to treating individuals with AAA has been challenged by the arrival of a new, minimally invasive technique: endovascular stent grafting of AAA, known as endovascular aneurysm repair, or EVAR. This technique, first described by Parodi in 1991, involves the placement of a tubular graft within the aneurysm sac (bulge), which is anchored in place using metallic stents (Parodi 1991). The aim is to exclude the aneurysm from within, thus preventing further expansion and rupture. The procedure is currently performed via arteriotomies (small holes in an artery to permit access) made in the groin arteries (usually the femoral arteries), using catheters and guidewires, and imaging with arteriography to position the stent‐graft device at the site of the aneurysm. Regional, rather than general, anaesthesia can be used, particularly in individuals for whom general anaesthesia is a relative contraindication.

How the intervention might work

There has been much development of these stent‐grafts in recent years and there are three main configurations of grafts available for use: tube grafts, aorto‐bi‐iliac grafts and aorto‐uni‐iliac grafts. Choice of graft configuration depends on operator experience and the anatomical type of aneurysm to be treated. The aortic tube graft is no longer used because it is unusual for there to be sufficient normal aorta below the infrarenal AAA to which to anchor the lower end of the stent‐graft. In addition, the distal aorta tends to enlarge with these stent‐grafts over time, resulting in the return of blood flow into the aneurysm sac (endoleak) at the distal fixation site. The aorto‐bi‐iliac device is the most commonly used device and is most readily available worldwide. The aorto‐uni‐iliac graft configuration involves the person with AAA having a cross‐over graft to maintain perfusion to both lower limbs. This configuration has the advantage that it can treat a large proportion of aneurysms, but currently it is suitable for use with only approximately 60% of all AAAs (Armon 1998).

Most grafts now in use are commercially produced, either custom made for individuals, or coming in a range of sizes so that a suitable device can be obtained 'off the shelf'. The majority of commercially produced devices are of the aorto‐bi‐iliac configuration, although aorto‐uni‐iliac devices can be produced as custom‐made devices on an individual basis, if required. Previously, some centres used improvised devices constructed from available graft materials and endovascular stents; these were usually of the aorto‐uni‐iliac configuration.

Since Parodi's landmark publication (Parodi 1991) there has been much interest in the EVAR technique. Potential advantages of this 'less invasive' technique over conventional OSR include:

reduced time under general or regional anaesthesia;
avoidance of arterial cross‐clamping, thus decreasing disruption of blood flow to vital organs and the lower extremities;
elimination of the pain and trauma of major abdominal surgery, enabling a shorter recovery time and potentially fewer respiratory complications;
reduced length of hospital stay;
reduced length of stay on an intensive care unit;
reduced blood loss.

All the above have the potential to reduce the morbidity and mortality of AAA repair. The potential cost savings from reduced use of hospital facilities are offset by the cost of the stent‐graft, which, in the UK, is approximately GBP5000, depending on the device used.

Why it is important to do this review

AAA can be treated using OSR or EVAR, and in those individuals considered unfit for surgery, a conservative management option is available in current practice. It is however, unclear as to which is the best option; for example, EVAR has earlier survival advantage compared to OSR but its longevity is unknown. It is therefore necessary to understand clearly the short‐, intermediate‐ and long‐term risks or benefits of the available options as this has implications for clinical practice.

This review draws together the available trial evidence to assess the advantages and disadvantages of EVAR compared with conventional OSR in individuals with AAA considered fit for surgery, and with conservative care (no intervention) in those considered unfit to undergo OSR.

Objectives

To assess the effectiveness of EVAR versus conventional OSR in individuals with AAA considered fit for surgery, and EVAR versus best medical care for those considered unfit for surgery. This was determined by the effect on short, intermediate and long‐term mortality, endograft related complications, re‐intervention rates and major complications.

Methods

Criteria for considering studies for this review

Types of studies

Prospective randomised controlled trials (RCTs) comparing EVAR with OSR in individuals considered fit for surgery, and EVAR with best medical care in individuals considered unfit for surgery. We excluded studies with inadequate data or using an inadequate randomisation technique.

Types of participants

All individuals with an AAA diagnosed by ultrasound or computed tomography (CT) in whom treatment was felt to be indicated. We excluded studies in which the size of aneurysm was not clear. We considered only individuals with asymptomatic AAA undergoing elective aneurysm treatment; we did not consider individuals undergoing emergency repair of an aneurysm.

Types of interventions

The primary intervention was elective EVAR repair of AAA. This can be performed with a variety of devices that fall into two main groups: aorto‐bi‐iliac devices and aorto‐uni‐iliac devices. We considered all device types. We compared EVAR repair with conventional OSR treatment in individuals considered fit for surgery, and with best medical care in those considered unfit for surgery. Complex and hybrid endovascular techniques (including fenestrated EVAR) were not considered in this review.

Types of outcome measures

Primary outcomes

Mortality and aneurysm‐related mortality rates: short term (30‐day or inhospital mortality), intermediate (up to four years from randomisation) and long term (beyond four years).
Endograft‐related complications (e.g. endoleak, reintervention (defined as the rate of any secondary intervention after the primary repair ‐ EVAR or OSR)
Major complications (e.g. those that altered management of the individual (myocardial infarction, stroke, renal failure, bowel ischaemia, pulmonary complications etc.)

Secondary outcomes

Minor complications
Health‐related quality of life (HRQoL): as measured using standardised questionnaires
Economic analysis: based on an analysis of costs, not charges

Search methods for identification of studies

We did not apply any language restrictions or any restrictions regarding publication status.

Electronic searches

The Cochrane Peripheral Vascular Diseases (PVD) Group Trials Search Co‐ordinator (TSC) searched the Specialised Register (January 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12, part of The Cochrane Library, www.thecochranelibrary.com. See Appendix 1 for details of the search strategy used to search CENTRAL. The Specialised Register is maintained by the TSC and is constructed from weekly electronic searches of MEDLINE, EMBASE, CINAHL and AMED, and through handsearching of relevant journals. The full list of the databases, journals and conference proceedings that were searched, as well as the search strategies used, are described in the Specialised Register section of the Cochrane Peripheral Vascular Diseases Group module in The Cochrane Library (www.thecochranelibrary.com).

The TSC also searched the following trial databases for details of ongoing and unpublished studies using the terms (aneurysm and abdominal and open and endovascular):

World Health Organization International Clinical Trials Registry (http://apps.who.int/trialsearch/);
ClinicalTrials.gov (http://clinicaltrials.gov/);
Current Controlled Trials (http://www.controlled‐trials.com/).

Searching other resources

We searched the reference lists of articles retrieved by electronic searches for additional citations.

In addition, we checked various health service research‐related resources via the internet. These included health economics and Health Technology Assessment organisations and guideline‐producing agencies (e.g. National Institute for Health and Clinical Excellence (NICE) and Scottish Intercollegiate Guidelines Network). We sought further trial reports through examination of the proceedings from the following meetings:

Vascular Society of Great Britain and Ireland (2004 to 2012);
Association of Surgeons of Great Britain and Ireland (2004 to 2012);
British Society of Interventional Radiology (2004 to 2012).

Data collection and analysis

Selection of studies

Three reviewers (SCVP, RJ and RC) independently evaluated trials, considered them for inclusion and assessed trial quality. Any disagreements were resolved by discussion.

Data extraction and management

Three reviewers (SCVP, RJ and RC) independently evaluated trials for appropriateness for inclusion and extracted data using pro forma designed by the Cochrane PVD Group.

Assessment of risk of bias in included studies

Three reviewers (SCVP, RJ and RC) independently assessed the quality of the included studies using the 'Risk of bias' tool developed by The Cochrane Collaboration (Higgins 2011). This tool provides a standard protocol for allowing judgements to be made on sequence generation, allocation methods, blinding, incomplete outcome data, selective outcome reporting and any other relevant biases. For each of these six items we assessed the risk of bias as 'low risk', 'high risk' or 'unclear risk', with the 'unclear risk' of bias category being used to indicate either a lack of information or uncertainty over the potential for bias.

Measures of treatment effect

We used odds ratios (OR) with a 95% confidence interval (CI) as the measure of effect for each dichotomous outcome. Where there were sufficient data, we calculated a summary statistic for each outcome using either a fixed‐effect or random‐effects model, depending on the presence of heterogeneity. We analysed continuous scales of measurement in a continuous form (i.e. mean difference with 95% CI).

Unit of analysis issues

For this review, we considered each participant as an individual unit of analysis.

Dealing with missing data

Where possible, we conducted analyses on an intention‐to‐treat (ITT) basis. The outcome data required were available from all trials. Due to the difficulty in identifying participants who died within the 30 days before the intervention, we did not analyse short‐term mortality on an ITT basis. We used ITT analyses for the intermediate‐ and long‐term outcomes.

Assessment of heterogeneity

We noted heterogeneity in the data and cautiously explored reasons for this using previously identified study characteristics, particularly assessments of quality. We used the I² statistic to assess heterogeneity, with an I² statistic of 25% to 50% indicating low heterogeneity, 50% to 75% indicating moderate heterogeneity and over 75% indicating significant heterogeneity. We used a random‐effects model when the I² statistic was greater than 50%.

Assessment of reporting biases

We did not perform a funnel plot to assess reporting bias because we included fewer than 10 studies (Higgins 2011).

Data synthesis

Where direct comparisons could be made, we calculated OR. We tested studies for heterogeneity and, if the I² statistic was greater than 50%, used a random‐effects model; otherwise we used a fixed‐effect model. We tabulated data that could not be collated. We performed statistical analyses according to the guidelines for reviews outlined in the Cochrane PVD Group's module using RevMan Software (version 5.2.3). With the available results it was not possible to perform time‐to‐event analyses.

Subgroup analysis and investigation of heterogeneity

The two main comparisons were the outcomes between OSR and EVAR in fit (low to moderate risk) patients and the outcomes between EVAR and 'no‐intervention' in unfit (high risk) surgical patients. We undertook no subgroup analyses.

Sensitivity analysis

We undertook no sensitivity analyses as there were no included studies with poor methodological quality.

Results

Description of studies

Results of the search

Figure 1 ‐ PRISMA flow diagram.

Included studies

Four trials comparing EVAR with OSR (ACE; DREAM; EVAR1; OVER) and one trial comparing EVAR with no intervention (EVAR2) fulfilled the inclusion criteria.

The specific details of each included study can be found in the 'Characteristics of included studies’ table.

EVAR1 was a multicentre RCT carried out in 37 UK centres that compared outcomes following EVAR and OSR in individuals considered fit for conventional surgical repair. A total of 1252 individuals aged 60 years or older with an AAA size of at least 5.5 cm in size were recruited between 1 September 1999 and 31 August 2004. A total of 626 individuals each were randomised to receive EVAR or OSR using a permuted block method. Mean (standard deviation (SD)) age was 74.1 (6.1) years and mean AAA size was 6.4 (0.9) cm; the male:female ratio was 10:1. Participants were followed up for a median (interquartile range (IQR)) of 6.0 (3.9 to 7.3) years. After randomisation, 12 individuals in the EVAR group and 19 in the OSR group died before they underwent the procedure. Five participants in the OSR group refused surgery and the procedure was postponed for one participant in each of the EVAR and OSR groups. Eight participants in the OSR group and nine in the EVAR group were lost to follow up. Analysis was ITT. All‐cause mortality was the primary outcome; secondary outcomes included aneurysm‐related mortality, postoperative complications, HRQoL, cost‐effectiveness and durability.

The Dutch Randomised Endovascular Aneurysm Management (DREAM) trial recruited 351 individuals at 26 Dutch and four Belgian centres between 2000 and 2003. A total of 173 participants were randomised to undergo EVAR and 178 to undergo OSR. Four participants declined the procedure postrandomisation (three in the OSR group versus one in the EVAR group) and one participant in each of the OSR and EVAR groups died before surgery. All participants were followed‐up for five years, with an overall 6.4 median years of follow up. All‐cause and aneurysm‐related mortality, procedural complications and reintervention rates were the outcomes assessed. Mean aneurysm size was 7.1 cm and the male:female ratio was 10:1.

Open Versus Endovascular Repair (OVER) was a multicentre RCT conducted at 42 Veteran Affairs Medical centres in the USA. Between October 2002 and October 2008, 881 individuals aged 49 years or older with a AAA of at least 4.5 cm in size were randomised to undergo EVAR (n = 444) or OSR (n = 437). In the EVAR group, two refused repair, two died before surgery, one repair was aborted and 12 participants underwent open repair. In the OSR group, four refused repair, three repairs were aborted, one participant died before repair and 13 underwent EVAR. The intended follow‐up period was until 2011. All‐cause mortality was the primary outcome. Secondary outcomes included procedural failure, short‐term morbidity, inhospital and intensive care stay, HRQoL and erectile dysfunction.

The Anevrysme de l'aorte abdominale, Chirurgie versus Endoprosthese (ACE) trial was a French multicentre trial that randomised individuals with AAA in whom open surgery was considered a low‐to‐medium risk procedure to either EVAR or OSR. Of the 306 individuals recruited between 2003 and 2008, seven withdrew consent and were excluded. A total of 149 participants were randomised to OSR and 150 to EVAR. Seventeen participants in the OSR group underwent EVAR whereas four in the EVAR group underwent OSR, predominantly due to individual preference. One participant in the OSR group did not undergo surgery. ITT analysis was used. All‐cause mortality and major adverse events (myocardial infarction, permanent stroke, permanent haemodialysis, major amputation, paraplegia and bowel infarction) were the main outcome measures. The reintervention rate and minor complications were the secondary outcome measures. Participants were followed up for a median of three years.

Unlike the aforementioned trials, EVAR2 assessed whether EVAR improves outcomes in individuals considered unfit for conventional OSR. Between September 1999 and August 2004, 404 high‐risk surgical individuals with a mean (SD) age of 76.8 (6.5) years and a mean AAA size of 6.7 (1.0) cm were recruited. Participants were allocated to receive no intervention (n = 207) or EVAR (n = 197). In the EVAR group, 18 participants died before surgery, nine due to a ruptured aneurysm. In the no‐intervention group, 70 participants underwent EVAR. The median (IQR) time from randomisation to surgery was 244 (83 to 643) days and 55 (38 to 77) days in the no‐intervention and EVAR groups, respectively. Median (IQR) follow up was 3.6 (1.3 to 5.4) years, with fewer than 1% of participants lost to follow‐up.

Excluded studies

We excluded seven studies from the review and reasons for this are detailed in 'Characteristics of excluded studies'.

Risk of bias in included studies

We included five randomised trials dating from between 1999 and 2008 in the review. We assessed the risk of bias across all included studies using the RevMan 'Risk of bias' assessment tool. All studies were of high quality with good randomisation and allocation concealment, reported all predefined outcomes and used ITT analyses; we therefore considered them at low risk of bias. Further details are shown in Figure 2 and Figure 3.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

Allocation in all trials was of acceptable standards, with allocation made only after receiving baseline participant data.

Blinding

Due to the nature of the intervention, participants and operators were not blinded to the treatment; however, individuals who assessed outcomes were blinded in the DREAM and OVER trials.

Incomplete outcome data

All studies used ITT analysis and reported on all recruited participants.

Selective reporting

All studies reported their predefined outcomes and hence we assessed the risk of reporting bias as minimal. However, not all trials reported the incidence of incisional hernia following OSR and the interventions needed to repair those hernias. This information would be useful in determining the reintervention rate after OSR.

Other potential sources of bias

The EVAR1 and DREAM trials recruited participants between 1999 and 2004, whereas the OVER and ACE trials recruited participants between 2002 and 2008. There may, therefore, be some bias with regards to the EVAR devices used in these studies, as advanced devices were available for use in the later OVER and ACE trials.

Effects of interventions

EVAR versus OSR in the management of surgically fit participants

All‐cause mortality

All four RCTs reported short‐term (30‐day or inhospital) and intermediate mortality, whereas three trials (EVAR1, DREAM and OVER) reported long‐term mortality.

Short‐term (30‐day or inhospital) mortality (comparison 1.1)

All four RCTs reported short‐term mortality. Some participants died before surgery or did not undergo the intervention. Hence, we excluded these individuals from the analysis of short‐term mortality. Intention‐to‐treat analysis was performed for intermediate and long‐term mortality.

For this analysis we used inhospital mortality data. There was no significant heterogeneity among trials. Short‐term mortality was significantly lower in the EVAR group (1.4%) than in the OSR group (4.2%) (P < 0.0001) (OR 0.33, 95% CI 0.20 to 0.55) (Analysis 1.1).

1.1 — Comparison 1 EVAR versus OSR in the management of fit individuals: all‐cause mortality, Outcome 1 Short term mortality (30‐day or in‐hospital) (excluding participants who died before surgery and those who did not undergo any intervention).

Intermediate (up to four years) mortality (comparison 1.2)

Mortality at intermediate follow up (up to four years, including those who died prior to intervention; ITT analysis) was reported by all trials. EVAR1 and DREAM reported four‐year outcomes, OVER reported two‐year outcomes and ACE reported three‐year follow up data. Intermediate follow‐up data was available for 1393 participants randomised to EVAR and 1390 randomised to OSR. There was no significant heterogeneity among trials (I² = 7%). There was no significant difference in mortality at follow up, with 221 (15.8%) and 237 (17%) deaths in the EVAR and OSR groups, respectively (OR 0.92, 95% CI 0.75 to 1.12; P = 0.40) (Analysis 1.2).

1.2 — Comparison 1 EVAR versus OSR in the management of fit individuals: all‐cause mortality, Outcome 2 Intermediate mortality (up to 4 years, ITT analysis).

Long‐term mortality (comparison 1.3)

Long‐term mortality data (ITT analysis) were reported for the EVAR1, DREAM and OVER trials for 1243 participants randomised to EVAR and 1241 randomised to OSR. Heterogeneity among trials was minimal (I² = 0%). There was no significant difference in long‐term mortality between groups, with 464 (37.3%) deaths in the EVAR group and 470 (37.8%) deaths in the OSR group (OR 0.98, 95% CI 0.83 to 1.15; P = 0.78) (Analysis 1.3).

1.3 — Comparison 1 EVAR versus OSR in the management of fit individuals: all‐cause mortality, Outcome 3 Long term mortality (beyond 4 years, ITT analysis).

Aneurysm‐related mortality

Short‐term aneurysm‐related mortality was not reported by all studies; intermediate‐ and long‐term results are presented only.

Intermediate AAA‐related mortality (comparison 2.1)

Intermediate (up to four years) AAA‐related mortality outcomes were reported by all four trials. There was moderate‐to‐high heterogeneity among trials (I² = 53%); hence, a random‐effects model was used. At intermediate follow up, aneurysm‐related mortality was slightly lower in the EVAR group with 40 deaths (n = 1393) compared to 60 deaths in the OSR group (n = 1390) (OR 0.64, 95% CI 0.29 to 1.44; P = 0.28) (Analysis 2.1).

2.1 — Comparison 2 EVAR versus OSR in the management of fit individuals: AAA‐related mortality, Outcome 1 Intermediate AAA‐related mortality (up to four years).

Long‐term AAA‐related mortality (comparison 2.2)

Long‐term follow‐up of the EVAR1, DREAM and OVER trials found no significant difference between the groups with regard to long‐term AAA‐related mortality (OR 0.74, 95% CI 0.50 to 1.08; P = 0.12) (Analysis 2.2). It is noteworthy that there were no deaths in the DREAM trial between the intermediate and final follow ups.

2.2 — Comparison 2 EVAR versus OSR in the management of fit individuals: AAA‐related mortality, Outcome 2 Long term AAA‐related mortality (beyond 4 years).

AAA‐related reintervention rate

Reintervention rates were reported in all four trials. In the DREAM trial, the reintervention rate, up to nine months after randomisation, was almost three times higher in the EVAR group than in the OSR group (HR 2.9, 95% CI 1.1 to 6.2, P = 0.03); thereafter there was no difference between groups (HR 1.1, 95% CI 0.1 to 9.3, P = 0.95).

Reintervention at intermediate follow up (comparison 3.1)

Reintervention data at intermediate follow up were available for the EVAR1, OVER and ACE trials. There was significant heterogeneity among trials (I² = 89%). The pooled estimate, using a random‐effects model, showed a significantly higher reintervention rate in the EVAR group than in the OSR group (OR 2.56, 95% CI 1.04 to 6.33; P = 0.04) (Analysis 3.1).

3.1 — Comparison 3 EVAR versus OSR in the management of fit individuals: reintervention, Outcome 1 Intermediate reintervention (up to four years).

Reintervention at long‐term follow up (comparison 3.2)

Long‐term follow up data on reinterventions was available from the DREAM, EVAR1 and OVER trials. There was moderate‐to‐high heterogeneity among trials (I² = 85%). The pooled estimate, using a random‐effects model, found that the reintervention rate was significantly higher in the EVAR group (23.4%) than in the OSR group (13.1%) (OR 1.98, 95% CI 1.12 to 3.51; P = 0.02) (Analysis 3.2).

3.2 — Comparison 3 EVAR versus OSR in the management of fit individuals: reintervention, Outcome 2 Long term reintervention (beyond 4 years).

It is important to note that the numbers presented are the numbers of individuals who needed reintervention rather than the numbers of reintervention procedures, as few individuals needed more than one intervention. In the OVER trial, 148 and 105 procedures were performed in 98 EVAR and 78 OSR participants, respectively.

Endograft‐related complications

See Analysis 4.1.

4.1. Analysis.

Comparison 4 EVAR versus OSR in the management of fit individuals: endograft‐related complications, Outcome 1 Endograft‐related complications.

Endograft‐related complications
Study	Any complication	Endoleaks	Graft migration
ACE	41 (N = 150)	(N = 150) Type I = 10 (7%) Type II = 31 (21%)	Not reported
DREAM	48 (N = 173)	(N = 173) Type I = 12 (7%) Type II = 8 (5%)	7 (4%)
EVAR1	282 (N = 626)	(N = 529) Type I = 27 (5%) Type II = 79 (15%) Type III = 8 (1.5%) Unspecified = 4 (0.75%)	12 (2%)
OVER	110 (N = 444)	(N = 444) Overall = 110 (25%)	Not reported

Erectile dysfunction
Study	Erectile dysfunction measure	EVAR	OSR
ACE	Basic assessment ‐‐ no questionnaire used	7 (4.7%) patients	11 (7.4%) patients
OVER	5‐item International Index of Erectile dysfunction (IIEF) (Follow up data presented a mean difference from baseline)	Baseline: 11.4 (8.7) 1 year: ‐2.5 (8.3) 2 years: ‐3.0 (8.5)	Baseline: 10.3 (8.8) 1 year: ‐2.3 (7.8) 2 year: ‐2.9 (8.5)

Quality of Life using SF‐36 and EQ‐5D
Study	QOL Measure	Components	Baseline score EVAR	Baseline score OSR	Follow up scores
EVAR1	SF‐36	Mental Component Score (MCS) (Mean (SD))	EVAR: 43.59 (6.79)	OSR: 43.95 (6.73)	EVAR 0‐3 months: 43.86 (7.02) EVAR 3‐12 months: 44.64 (6.67) EVAR 12‐24 months: 44.54 (6.43) OSR 0‐3 months: 44.04 (7.31) OSR 3‐12 months: 44.18 (6.81) OSR 12‐24 months: 44.76 (6.81)
EVAR1	SF‐36	Physical Component Score (PCS) (Mean (SD))	EVAR: 39.92 (5.92)	OSR: 39.83 (5.90)	EVAR 0‐3 months: 37.82 (5.92) EVAR 3‐12 months: 37.77 (5.73) EVAR 12‐24 months: 38.17 (5.83) OSR 0‐3 months: 36.14 (5.45) OSR 3‐12 months: 37.81 (5.84) OSR 12‐24 months: 38.33 (5.78)
EVAR1	EQ‐5D	Index score (Mean (SD))	EVAR: 0.75 (0.22)	OSR: 0.77 (0.23)	EVAR 0‐3 months: 0.73 (0.21) EVAR 3‐12 months: 0.71 (0.25) EVAR 12‐24 months: 0.74 (0.24) OSR 0‐3 months: 0.67 (0.25) OSR 3‐12 months: 0.73 (0.23) OSR 12‐24 months: 0.75 (0.25)
OVER	SF‐36	Mental Component Score (MCS)	EVAR: 50.6 (10.9)	OSR: 51.7 (10.4)	EVAR 1 year: ‐0.77 (10.2) EVAR 2 years: ‐0.01 (10.0) OSR 1 year: ‐0 (10.0) OSR 2 years: ‐0.93 (9.8) (mean differences from baseline)
OVER	SF‐36	Physical Component Score (PCS)	EVAR: 40.5 (10.4)	OSR: 40.1 (10.5)	EVAR 1 year: ‐1.2 (9.8) EVAR 2 years: ‐2.2 (10.2) OSR 1 year: ‐1.2 (10.1) OSR 2 years: ‐2.0 (10.8) (mean differences from baseline)
OVER	EQ‐5D	Index score (Mean (SD))	EVAR: 0.79 (0.16)	OSR: 0.79 (0.16)	EVAR 1 year: ‐0.02 (0.16) EVAR 2 years: ‐0.01 (0.19) OSR 1 year: ‐0 (0.17) OSR 2 years: ‐0.02 (0.16) (mean differences from baseline)

#1	MeSH descriptor: [Endovascular Procedures] explode all trees	5267
#2	MeSH descriptor: [Stents] explode all trees	2939
#3	MeSH descriptor: [Vascular Surgical Procedures] this term only	617
#4	MeSH descriptor: [Blood Vessel Prosthesis] explode all trees	432
#5	MeSH descriptor: [Blood Vessel Prosthesis Implantation] this term only	456
#6	endovasc*:ti,ab,kw	688
#7	endostent*:ti,ab,kw	1
#8	stent*:ti,ab,kw	4355
#9	EVAR:ti,ab,kw	63
#10	EVRAR:ti,ab,kw	1
#11	percutaneous:ti,ab,kw	5781
#12	TEVAR:ti,ab,kw	9
#13	(endoprosthe* or endograft*):ti,ab,kw	206
#14	Palmaz:ti,ab,kw	91
#15	Zenith or Dynalink or Hemobahn or Luminex* or Memotherm or Wallstent:ti,ab,kw	105
#16	Viabahn or Nitinol or Hemobahn or Intracoil or Tantalum:ti,ab,kw	116
#17	#1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16	12362
#18	MeSH descriptor: [Aortic Aneurysm] explode all trees	693
#19	aneurysm* near/4 (abdom* or thoracoabdom* or thoraco‐abdom* or aort*)	996
#20	(aort* near/3 (ballon* or dilat* or bulg*))	50
#21	AAA	389
#22	#18 or #19 or #20 or #21	1151
#23	#17 and #22 in Trials	259

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Short term mortality (30‐day or in‐hospital) (excluding participants who died before surgery and those who did not undergo any intervention)	4	2723	Odds Ratio (M‐H, Fixed, 95% CI)	0.33 [0.20, 0.55]
2 Intermediate mortality (up to 4 years, ITT analysis)	4	2783	Odds Ratio (M‐H, Fixed, 95% CI)	0.92 [0.75, 1.12]
3 Long term mortality (beyond 4 years, ITT analysis)	3	2484	Odds Ratio (M‐H, Fixed, 95% CI)	0.98 [0.83, 1.15]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Intermediate AAA‐related mortality (up to four years)	4	2783	Odds Ratio (M‐H, Random, 95% CI)	0.64 [0.29, 1.44]
2 Long term AAA‐related mortality (beyond 4 years)	3	2484	Odds Ratio (M‐H, Fixed, 95% CI)	0.74 [0.50, 1.08]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Intermediate reintervention (up to four years)	3	2432	Odds Ratio (M‐H, Random, 95% CI)	2.56 [1.04, 6.33]
2 Long term reintervention (beyond 4 years)	3	2484	Odds Ratio (M‐H, Random, 95% CI)	1.98 [1.12, 3.51]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Non‐fatal stroke	3	2432	Odds Ratio (M‐H, Fixed, 95% CI)	0.81 [0.50, 1.31]
2 Fatal stroke	2	1603	Odds Ratio (M‐H, Fixed, 95% CI)	0.81 [0.42, 1.55]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Pulmonary complications	2	650	Odds Ratio (M‐H, Fixed, 95% CI)	0.36 [0.17, 0.75]
2 Pulmonary related deaths	3	2484	Odds Ratio (M‐H, Fixed, 95% CI)	0.69 [0.45, 1.05]

Methods	Study design: Multicentre RCT Method of randomisation: Stratified by centre Exclusions post randomisation: 7 (due to withdrawal from consent) Losses to follow up: 8 (EVAR = 3, OSR = 5) Intention‐to‐treat analysis: Yes
Participants	Country: France Setting: Hospital (25 centres) Recruitment: 2003 to 2008 Number: 306 (149 OSR, 150 EVAR) Age: 69 ± 7 years (mean) Sex: 296 male / 3 female Inclusion criteria: Consisted of both anatomical criteria and clinical assessment. ‐ Anatomical criteria (based on CT scan findings): AAA > 5 cm in men (or) > 4.5 cm in women (or) common iliac artery aneurysm > 3.0 cm AND upper neck free of major thrombus or calcification AND ≥ 1.5 cm length AND angle between the neck and the axis of the aneurysm < 60° AND iliac arteries compatible with the introducer sheath ‐ Clinical assessment: Participants graded as categories 0 to 2 of the comorbidity score of the SVS/AAVS Exclusion criteria: Previous abdominal aortic surgery Ruptured aneurysm Mycotic aneurysm Severe Iodine allergy Life expectancy deemed < 6 months, (or) category 3 of the SVS/AAVS classification
Interventions	Treatment: EVAR Control: OSR
Outcomes	Primary: All‐cause mortality, major adverse events (myocardial infarction, permanent stroke, permanent haemodialysis, major amputation, paraplegia and bowel infarction) Secondary: Vascular reinterventions and minor complications
Notes	Trial was conducted in individuals considered to be at low‐to‐medium risk of surgery Reinterventions for incisional hernia repair were not recorded In the EVAR group, 4 participants each had surgery under local and epidural anaesthesia. Remainder all had surgery under general anaesthesia
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation done based on centre
Allocation concealment (selection bias)	Low risk	Allocation only notified < 24 hours
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Blinding of participants and operating surgeons not feasible in such a study
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	No clear data available
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Presented results based on intention‐to‐treat and presented final follow up results. All participants accounted for
Selective reporting (reporting bias)	Low risk	Reported on all predefined outcomes
Other bias	Low risk	None identified

Study	Reason for exclusion
CAESAR Trial	RCT comparing surveillance and selective surgical treatment for abdominal aortic aneurysm less than 5.5 cm in diameter versus early endovascular treatment. Excluded as EVAR was compared with surveillance but not open surgery but trial was not conducted in 'unfit' individuals. In addition the aneurysms were of small diameter.
Cuypers 2001	A small RCT comparing cardiac response between EVAR and OSR. The randomisation method and allocation concealment were unclear. Mortality and long‐term outcomes were not the primary endpoints. Hence, the trial may not be powered to determine the outcomes considered for this review.
ECAR study 2010	RCT comparing EVAR versus OSR in participants with ruptured aorto‐iliac aneurysms.
IMPROVE trial	RCT comparing EVAR versus OSR in participants with ruptured AAA.
Lottman 2004	This study randomised participants in a 3:1 format, where 57 participants were randomised to EVAR and 19 to OSR. Further they present health‐related quality of life outcomes estimated at 3 months post surgery. The numbers of participants considered for study, especially in the OSR group, were small and the outcomes were estimated at 3 months only. Therefore, the results may not be a true representative of the effects of the interventions and hence the study was excluded from analysis.
PIVOTAL Trial	Study determined whether repair of small aneurysms is superior to surveillance with respect to the frequency of rupture or aneurysm‐related death.
Soulez 2005	A small RCT (n = 40), comparing pain and quality of life in participants undergoing EVAR with those undergoing OSR. Randomisation method and allocation concealment were unclear. Mortality and long‐term outcomes were not the primary endpoints.

Trial name or title	NExT ERA: National Expertise Based Trial of Elective Repair of Abdominal Aortic Aneurysms: A Pilot Study
Methods
Participants	All participants with an AAA considered to require non‐urgent repair after assessment by one of the participating surgeons will be considered.
Interventions	Open surgical repair or EVAR treatment of AAA
Outcomes	Mortality from the time of randomisation until hospital discharge or 30 days after surgery  Non‐fatal myocardial infarction  End‐organ ischaemic event rates (including renal failure, limb ischaemia, bowel ischaemia, non‐fatal stroke)  Reintervention  Quality of life  Success of repair  Mortality at 6 months
Starting date	September 2006
Contact information	Tara M Mastracci, MD, FRCSC
Notes	NCT00358085: Not yet recruiting, no verification of information since 2006

PERMALINK

Endovascular repair of abdominal aortic aneurysm

Sharath Chandra Vikram Paravastu

Rubaraj Jayarajasingam

Rachel Cottam

Simon J Palfreyman

Jonathan A Michaels

Steven M Thomas

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Results

Description of studies

Results of the search

1.

Included studies

Excluded studies

Risk of bias in included studies

2.

3.

Allocation

Blinding

Incomplete outcome data

Selective reporting

Other potential sources of bias

Effects of interventions

EVAR versus OSR in the management of surgically fit participants

All‐cause mortality

Short‐term (30‐day or inhospital) mortality (comparison 1.1)

1.1. Analysis.

Intermediate (up to four years) mortality (comparison 1.2)

1.2. Analysis.

Long‐term mortality (comparison 1.3)

1.3. Analysis.

Aneurysm‐related mortality

Intermediate AAA‐related mortality (comparison 2.1)

2.1. Analysis.

Long‐term AAA‐related mortality (comparison 2.2)

2.2. Analysis.

AAA‐related reintervention rate

Reintervention at intermediate follow up (comparison 3.1)

3.1. Analysis.

Reintervention at long‐term follow up (comparison 3.2)

3.2. Analysis.

Endograft‐related complications