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Cochrane Database of Systematic Reviews Protocol - Intervention

Endovascular versus conventional open surgical repair for thoracoabdominal aortic aneurysms

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Abstract

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

To assess the effectiveness and safety of endovascular repair versus conventional open surgical repair (OSR) used in the management of thoracoabdominal aorta aneurysms (TAAAs).

Background

Description of the condition

Conventionally, an aneurysm is considered a widening, or dilation of a blood vessel 50% greater than the original vessel diameter. Aneurysms affecting the aorta can be regionally classified into three main categories; isolated thoracic, isolated abdominal and thoracoabdominal (where the aneurysm crosses the diaphragm and affects both the thoracic and abdominal aorta simultaneously). Aortic aneurysms are known to rupture at various sizes and rupture risk is influenced by numerous factors including wall stress, growth rate, gender, location of the aneurysm along the aorta and the presence of a connective tissue disorder (Bäck 2013; Kontopodis 2013). For further detail, see the Clinical Practice Guidelines of the European Society for Vascular Surgery (SVS) ‐ Management of Descending Thoracic Aorta Diseases (Riambau 2017). In the US alone, approximately 16,000 deaths per year are attributed to aortic aneurysms and up to 10% of these are thoracoabdominal in pathology, while the overall estimated prevalence of thoracoabdominal aortic aneurysms (TAAAs) rests at 5.9 cases per 100,000 person years (Barbour 2007; Choong 2010; Youssef 2014).

TAAAs were first classified by Crawford in 1986 and amended by Safi in 1999. The classifications include Type I to Type V based on the anatomical extension of the aneurysm or involvement of the thoracic and abdominal aorta (Fernandez‐Moure 2011; Safi 1999). Type I affects just below the left subclavian artery (LSA) to above the renal arteries, Type II originates distal to the LSA and ends below the renal arteries, Type III presents between the sixth intercostal space and ends inferior to the renal arteries, Type IV affects the aorta between the 12th intercostal space and the iliac bifurcation and Type V presents inferior to the sixth intercostal space and superior to the renal arteries (Fernandez‐Moure 2011).

Aneurysms affecting the thoracic aorta are considered difficult to detect until the point of rupture, with approximately 95% of people being asymptomatic while the TAAA silently increases in size. Consequently, for aneurysms exceeding 6.0 cm in diameter, the associated overall mortality rate for rupture is 97% to 100% (Elefteriades 2015; Rolph 2015).

Description of the intervention

Currently three surgical approaches to treat TAAAs exist; these include conventional open surgical repair (OSR), endovascular repair and hybrid repair (Clough 2012; Fehrenbacher 2012; Oderich 2012). The principle of OSR is to operate directly on the aorta by means of surgical exposure, while endovascular repair relies upon aneurysm exclusion through the delivery of a stent graft intravascularly from a peripheral access point to the local site of the aneurysm. The effectiveness of hybrid repair will not be investigated in this review as it will be investigated in another Cochrane Review.

Open surgical repair

OSR of TAAAs involves opening both the chest and abdomen through a long incision. The procedure requires cross‐clamping of the aorta and replacement of the aneurysmal segment with a synthetic graft with branches to the visceral arteries. Due to the clamping and excision of the diseased section of the aorta, distal reperfusion is required to offer protection from visceral, lower extremity and spinal cord ischaemia. Conventional OSR of TAAAs has been the gold standard since its introduction in 1955 (Kheirelseid 2014). Various centres have published mortality rates as high as 48.4% and postoperative spinal cord ischaemia rates up to 8.0% (Greenberg 2008; Rigberg 2006). Modern advances in surgical techniques for OSR including distal reperfusion and hypothermic circulatory arrest have helped reduce complications; however, issues relating to respiratory compromise, brain, spinal cord, cardiac and visceral ischaemia continue to pose significant concern (Riambau 2017).

Endovascular repair

Endovascular repair is considered a less invasive method of excluding an aneurysm by means of deploying stents inside the artery at the site of the aneurysm. The stents are within a delivery sheath which is guided from the arterial access site to the site of the aneurysm using a guidewire and fluoroscopic imaging techniques. Imaging is used throughout the procedure to locate important branches, which may necessitate either protection or stenting. Balloon inflation is often used to mould the sealing zones to the aorta and to improve apposition where stents overlap. Finally, completion angiography is used to confirm accurate placement as well as the absence of endoleaks (Singh 2014).

How the intervention might work

Although to date trial results using an endovascular repair technique for TAAA are promising (Ferrer 2015), surgical opinion is still divided on the overall benefits of this technique over OSR among the wider vascular community. OSR is considered the gold standard of treatment for TAAAs (Kheirelseid 2014). Intervention for TAAAs via an endovascular approach offers an alternative to the highly invasive OSR, while distal reperfusion, laparotomy or thoracotomy, aortic clamping and long hospital stay can be avoided. However, there remains concern regarding high rates of paraplegia, renal failure and visceral ischaemia as a result of branch occlusions following endovascular repair (Greenberg 2008).

Why it is important to do this review

We are undertaking this review as there is a need within the vascular community for greater information regarding the best surgical approach for the treatment of TAAAs. The management of this condition is complex due to its diagnosis, anatomy and repair procedures. In conjunction with the significantly high rates of postoperative complications, management continues to challenge vascular interventionalists worldwide. Evidence for endovascular and open surgical treatment has yet to demonstrate the most clinically effective method (Zanow 2014). To date, no Cochrane Review has assessed the effectiveness and safety of endovascular repair compared to the gold standard of conventional OSR.

Objectives

To assess the effectiveness and safety of endovascular repair versus conventional open surgical repair (OSR) used in the management of thoracoabdominal aorta aneurysms (TAAAs).

Methods

Criteria for considering studies for this review

Types of studies

We will include randomised controlled trials (RCTs) and controlled clinical trials (CCTs) assessing endovascular techniques and OSR techniques in the treatment of TAAAs.

Types of participants

We will include people with a primary TAAA of any type (Crawford Classifications Type I to V; see Description of the condition). Aneurysm formation post aortic dissection will not be included.

Types of interventions

We will include all studies comparing endovascular repair versus OSR. For both endovascular and OSR, there are a number of devices used and all device types will be included.

Types of outcome measures

The selection of primary and secondary outcomes was guided by the SVS reporting standards for thoracic endovascular aortic repair (TEVAR) (Fillinger 2010). The timepoints we expect to report will be primarily guided by the included studies, but will likely be 30 days, 12 months and 5 years unless otherwise stated.

Primary outcomes

  • Prevention of aneurysm rupture (participants without aneurysm rupture up to five years from intervention).

  • Aneurysm related mortality (30 days and 12 months).

  • All cause mortality.

  • Spinal cord ischaemia (paraplegia, paraparesis).

Secondary outcomes

(Adapted from Fillinger 2010.)

  • Visceral arterial branch compromise causing mesenteric ischaemia, and renal failure.

  • Rate of reintervention.

  • Presence of endoleak associated with aneurysm sac expansion.

  • Conversion to open repair.

Search methods for identification of studies

There will be no restrictions regarding language or publication status.

Electronic searches

The Cochrane Vascular Information Specialist (CIS) will search the following databases for relevant trials:

  • Cochrane Vascular Specialised Register;

  • Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online.

See Appendix 1 for details of the search strategy to be used to search CENTRAL.

The Cochrane Vascular Specialised Register is maintained by the CIS and is constructed from weekly electronic searches of MEDLINE Ovid, Embase Ovid, CINAHL, AMED and handsearching relevant journals. The full list of the databases, journals and conference proceedings that have been searched, and the search strategies used, are described in the Specialised Register section of the Cochrane Vascular module in the Cochrane Library (www.cochranelibrary.com).

In addition, the CIS will search the following trial registries for details of ongoing and unpublished studies:

Searching other resources

We will review citations of included papers identified from the search strategy described above.

Data collection and analysis

Selection of studies

Two review authors (JC and EPK) will independently screen all titles and abstracts identified from searches to identify those that might meet the inclusion criteria. We will retrieve the full text of studies identified as potentially relevant by at least one review author. The same review authors will independently screen full text articles for inclusion or exclusion. Any disagreements will be resolved by discussion or, if necessary, we will consult a third review author (NH). All studies excluded at the full text stage will be listed as excluded studies and reasons for their exclusion will be presented in the 'Characteristics of excluded studies' table. We will report the screening and selection process in an adapted PRISMA flowchart (Liberati 2009).

Multiple reports of one study will be collated so that the study, and not the report, is the unit of analysis.

Data extraction and management

Two review authors (JC and EPK) will independently extract data from the eligible studies using an adapted and piloted data extraction form provided by the Cochrane Vascular Group. Any disagreements will be resolved by discussion or if necessary, we will consult with a third review author (NH). One review author (JC) will enter extracted data into Review Manager 5 (RevMan 2014), and a second review author (NH) will check them for accuracy and consistency against the data extraction sheets.

We will aim to describe the studies according to the following:

  • trial design;

  • diagnosis of TAAA;

  • demographic characteristics of participants;

  • type of intervention (open and endovascular repair);

  • frequency of primary and secondary outcomes;

  • treatment centre.

Assessment of risk of bias in included studies

Two review authors (JC and EPK) will independently assess each study for risk of bias according to the following criteria, as recommended by the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011):

  • random sequence generation (selection bias);

  • allocation concealment (selection bias);

  • blinding of participants and personnel (performance bias)*;

  • blinding of outcome assessment (detection bias)*;

  • incomplete outcome data (attrition bias);

  • selective reporting (reporting bias);

  • other sources of bias.

We will judge all included studies as having low, high or unclear risk of bias on the basis of these criteria. We will resolve disagreements by discussion or, if necessary, we will consult with a third review author (NH).

*Due to the nature of the type of intervention, blinding of participants and personnel (i.e. participants, clinicians and outcome assessors) will not be possible, therefore, these domains will be deemed high risk of bias.

Measures of treatment effect

Dichotomous data

We will express the results for dichotomous outcome measures using risk ratio (RR) and associated 95% confidence intervals (CI) to reflect uncertainty of the point estimate of effects.

Continuous data

For continuous outcome measures, we will calculate mean and standard deviation (SD) with corresponding 95% CI. We will use standardised mean difference (SMD) with 95% CI to combine outcomes from trials that measure outcomes using different scales (Higgins 2011).

Time‐to‐event data

We will use survival analysis to report time‐to‐event data and the intervention effect expressed as a hazard ratio (HR) and associated 95% CIs. Methods used to analyse time‐to event data will be guided by those described by Parmar 1998 and Tierney 2007.

Unit of analysis issues

The unit of analysis will be each individual participant.

Dealing with missing data

We will record missing and unclear data for each included study. If possible, we will perform all analyses using an intention‐to‐treat approach, that is, we will analyse all participants and their outcomes within the groups to which they were allocated, regardless of whether they received the intervention. If necessary, we will contact study authors to request missing data.

Assessment of heterogeneity

We will assess the degree of heterogeneity by visual inspection of forest plots and by using the Chi² test for heterogeneity. We will assess heterogeneity of the overall results for the main outcomes using the Chi², I² and Tau² statistics, according to the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

We will regard statistical heterogeneity as substantial if the I² is greater than 50% and either the T² is greater than zero, or there is a low P value (less than 0.10) in the Chi² test for heterogeneity.

If we identify substantial clinical, methodological or statistical heterogeneity across included trials, we will not report pooled results from the meta‐analysis but will instead use a narrative approach to data synthesis. If we identify substantial heterogeneity, we will explore possible reasons by grouping trials that have similar populations.

Assessment of reporting biases

We will investigate publication bias using funnel plots, if there are 10 or more studies included in the review as recommended by the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Data synthesis

We will carry out statistical analysis using Review Manager 5 (RevMan 2014). We will use fixed‐effect meta‐analysis for synthesising data where it is reasonable to assume that trials are estimating the same underlying treatment effect. If there is clinical heterogeneity sufficient to expect that the underlying treatment effects differ between trials, or if substantial statistical heterogeneity is detected, we will use random‐effects meta‐analysis to produce an overall summary where the mean treatment effect is clinically meaningful.

Subgroup analysis and investigation of heterogeneity

Planned subgroup analyses will include:

  • Type I OSR versus endovascular treatment;

  • Type II OSR versus endovascular treatment;

  • Type III OSR versus endovascular treatment;

  • Type IV OSR versus endovascular treatment;

  • Type V OSR versus endovascular treatment;

  • connective tissue disorder versus non‐connective tissue disorder;

  • physician modified devices (chimney/parallel graft repairs) versus off the patient specific devices (branched/fenestrated repair);

  • intercentre efficacy.

Sensitivity analysis

We will repeat the analyses including high quality trials only. For this review, trials judged, as 'low risk of bias' for sequence generation and allocation concealment will be classified as high quality trials. We will also repeat the analyses including RCTs only.

'Summary of findings' table

We will prepare a 'Summary of findings' table for each comparison of endovascular repair versus OSR in participants with TAAA. We will include the outcomes detailed in the Types of outcome measures section. Please see Table 1 for an example of the planned 'Summary of findings' table. We will grade the quality of the evidence using criteria devised by the GRADE Working group (GRADE Working Group 2014) and use GRADEprofiler (GRADEpro) software (Guyatt 2008; Higgins 2011; Schünemann 2006). We will assign one of four levels of quality: high, moderate, low or very low based on overall risk of bias of the included studies, directness of the evidence, inconsistency of results, precision of the estimates and risk of publication bias.

Open in table viewer
Table 1. Is endovascular repair an effective treatment for TAAAs?

Endovascular repair compared with conventional open surgery for thoracoabdominal aortic aneurysms (TAAA)

Patient or population: people with a diagnosis of thoracoabdominal aortic aneurysm

Settings: hospital

Intervention: endovascular repair

Comparison: open surgical repair

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Open surgical repair

Endovascular repair

Prevention of aneurysm rupture (defined as number of participants without a rupture)

(5 years)

Aneurysm related mortality

(12 months)

All cause mortality

(5 years)

Spinal cord ischaemia (paraplegia, paraperesis)

(5 years)

Visceral arterial branch compromise causing, mesenteric ischaemia, and renal failure

(5 years)

Rate of reintervention

(5 years)

Conversion to open repair

(5 years)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Table 1. Is endovascular repair an effective treatment for TAAAs?

Endovascular repair compared with conventional open surgery for thoracoabdominal aortic aneurysms (TAAA)

Patient or population: people with a diagnosis of thoracoabdominal aortic aneurysm

Settings: hospital

Intervention: endovascular repair

Comparison: open surgical repair

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Open surgical repair

Endovascular repair

Prevention of aneurysm rupture (defined as number of participants without a rupture)

(5 years)

Aneurysm related mortality

(12 months)

All cause mortality

(5 years)

Spinal cord ischaemia (paraplegia, paraperesis)

(5 years)

Visceral arterial branch compromise causing, mesenteric ischaemia, and renal failure

(5 years)

Rate of reintervention

(5 years)

Conversion to open repair

(5 years)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Figures and Tables -
Table 1. Is endovascular repair an effective treatment for TAAAs?