Journal of Vascular Surgery
Volume 49, Issue 4 , Pages 1077-1080, April 2009

Endovascular repair of ruptured abdominal aortic aneurysm: A strategy in need of definitive evidence

  • Robert J. Hinchliffe, MD, MRCS

      Affiliations

    • St. George's Vascular Institute, London, United Kingdom
    • Corresponding Author InformationReprint requests: R. J. Hinchliffe, St George's Vascular Institute, 4th Floor, St. James Wing, St. George's Healthcare NHS Trust, Blackshaw Rd, London SW17 0QT, UK
    • ,
  • Janet T. Powell, PhD, FRCPath

      Affiliations

    • Vascular Surgery Research Group Imperial College, London, United Kingdom
    • ,
  • Nicholas J. Cheshire, MD, FRCS

      Affiliations

    • St Mary's Regional Vascular Unit, Imperial College Healthcare NHS Trust, London, United Kingdom
    • ,
  • Matthew M. Thompson, MD, FRCS

      Affiliations

    • St. George's Vascular Institute, London, United Kingdom

Received 3 February 2009; accepted 3 February 2009.

Jan D. Blankensteijn, MD, Section Editor

Article Outline

Introduction

Endovascular strategies have been increasingly used to manage patients with ruptured abdominal aortic aneurysm (AAA) in an attempt to improve patient survival. We analyzed the evidence to support such an approach.

Methods

We performed a systematic literature review of endovascular aneurysm repair (EVAR) of ruptured AAA from 1994 to 2009. The literature analyzed included systematic reviews and population-based studies of ruptured AAA.

Results

Seven systematic reviews were identified, all demonstrating from published data that patients with EVAR of ruptured AAA had significantly reduced mortality compared with controls. Six recently published population-based studies from the United States demonstrated low mortality rates associated with EVAR; however, only a small proportion of ruptured AAAs were treated by EVAR. Systematic reviews and population-based studies both raised concerns about patient selection and publication bias. Two randomized trials are in progress, and one is due to commence 2009.

Conclusions

The outcome of EVAR in a nonselected patient population remains unknown. One or more definitive randomized trials could provide the level I evidence to resolve these issues.

 

Most ruptured aneurysms worldwide are repaired by conventional open surgery, with a high operative mortality and intensive care therapies that are often costly. Some vascular surgery units, including our own, have instigated a strategy of using endovascular aneurysm repair (EVAR) for many patients presenting with ruptured abdominal aortic aneurysms (AAA) because of the potential benefits in improving survival.

Back to Article Outline

Methods 

We performed a systematic literature review between 1994 and 2009 using a Medline and EMBASE search of English language publications. Key words used were “ruptured aneurysm,” “EVAR,” and “endovascular aneurysm repair.” We also examined the Cochrane Central Register of Controlled Trials database (http://www.cochrane.org/) and two randomized trials registries for trials that are planned, in progress, or completed (ClinicalTrials.gov Web site at http://clinicaltrials.gov/ct2/home), and the International Standard Randomized Controlled Trial Number Register (http://www.isrctn.org/).

Our review focuses on the more recent data published in large population-based studies of ruptured AAA and includes systematic reviews and meta-analyses and the randomized trials that are planned or are in progress.

Back to Article Outline

Results 

We identified 40 case series, retrospective, and prospective studies. Some of these studies had control groups of patients undergoing open aneurysm repair (Table I). One pilot randomized trial and six recent population-based studies were from the United States.1, 2, 3, 4, 5, 6, 7 In the absence of randomized trial evidence, systematic reviews can be helpful. Recent reviews, seven within a 15-month period (2007 to 2008) that analyzed the contemporary literature, are subject to strong biases. Although each review substantially differed in design and inclusion criteria (each review analyzed between 10 and 34 studies), the mortality rates for EVAR reported in the controlled series were lower than the open controls.8, 9, 10, 11, 12, 13, 14

Table I. Data from published series from 1994 to 2009 where outcomes of endovascular repair for ruptured abdominal aortic aneurysms were compared with a control group undergoing open surgery
First authorYearStudy typePatients treated by EVAR, No.30-day mortality, %P
EVAROpen repair
Acosta2007Retrospective review563445.16
Alsac2005Case series1723.550.09
Anain2007Retrospective review301740.19
Arya2006Prospective intent-to-treat172447.14
Brandt2005Retrospective review11015NS
Castelli2005Retrospective review252025NS
Coppi2006Retrospective review333046NS
Franks2006Retrospective study211154NS
Hechelhammer2005Retrospective study3510.835NS
Hinchliffe2006Prospective randomized155353NS
Kapma2005Retrospective study401330NS
Lee2004Retrospective study137.6925NS
Mehta2006Prospective observation401851. . .
Moore2007Prospective observation20525NS
Najjer2007Retrospective review156.713.6NS
Ohki2000Retrospective study18100NS
Ockert2007Retrospective review293131<.99
Peppelenbosch2003Prospective study263150NS
Scharrer-Pamler2003Retrospective review2420.840NS
Vaddenini2005Retrospective study92226NS
Visser2006Retrospective review263131NS
Wibmera2008Retrospective review1625a29aNS
Yilmaz2002Retrospective review241734NS
Peppelenbosch2006Prospective study493539NS
Verhoeven2009Prospective observation3628.113.9.092
Sadat2009Prospective observation17617. . .

EVAR, Endovascular aneurysm repair; NS, not significant.

a90 day mortality figures quoted.

A consistent finding amongst all the reviews was study heterogeneity and patient selection bias. Not all open surgery controls were contemporaneous or well matched. A high proportion of studies did not indicate how many patients were turned down for EVAR on the basis of physiologic, morphologic, or other grounds. Significant publication bias existed, and standardized reporting criteria were lacking. Therefore, any meta-analysis should be interpreted with caution.

The United States population-based studies demonstrated a low uptake of EVAR for ruptured AAA. However, five of the six reported a significantly improved mortality rate in those undergoing EVAR (Table II).

Table II. Data from United States population-based studies on outcomes of ruptured abdominal aortic aneurysm
StudyStudy periodPopulationNo. (relative %)Mortality, %P
First authorEVAROpenEVAROpen
Greco32000-2003Calif, Fla, NJ, NYa290(5)5508(95)39.347.7.005
Lesperance42001-2004US (NIS)949(10)8982(90)3142<.001
Egorova21995-2004US (Medicare)1064(2.5)41969(97.5)30.4(HVC)38.4(HVC)<.05
57.7(LVC)56.4(LVC)<.05
Giles51993-2005bUS(NIS)2499(10.7)20836(89.3)32.340.8<.001
McPhee62001-2006US(NIS)3179(11.5)24571(88.5)31.740.7<.0001
Vogel72001-2005NJc82(12)618(88)45.152.4.21

LVC, Low-volume center; HVC, high-volume center; NIS, Nationwide Inpatient Sample.

aState-based data sets.

bComparative subset 2001-2005.

cState Inpatient Databases.

The Amsterdam (Acute Endovascular Treatment to Improve Outcome of Ruptured Aortoiliac Aneurysms [Ajax]) trial (ISRCTN66212637) was based rather optimistically on the recruitment of just 80 patients.15 With 80 patients, there was no significant difference in primary combined end point of 30-day mortality and serious morbidity. Recruitment, which was planned to stop in late 2007, has therefore been extended twice.

The Paris-based Ruptured Aorta-Iliac Aneurysms: Endo vs Surgery (ECAR) trial (NCT00577616) is similarly designed to recruit only those patients who are stable and morphologically suitable for EVAR. Unusually, patients are randomized according to the calendar week and the hospital at which they present.

The United Kingdom-based Immediate Management of the Patient with Rupture: Open Versus Endovascular Repair (IMPROVE) Trial (ISRCTN48334791), a study funded by the National Institute for Health Research Health Technology Assessment Programme, is set up to establish whether a strategy of preferential EVAR for ruptured AAA vs the current practice of open repair significantly reduces the 30-day and in-hospital mortality rate of ruptured AAA from the >45% for open repair to 30% for EVAR as the first approach. Trial recruitment will begin in centers across the United Kingdom and Europe in the summer of 2009 and should run for 3 years (Fig).

  • View full-size image.
  • Fig. 

    Design of IMPROVE (Immediate Management of the Patient with Rupture Open Versus Endovascular repair) Trial (ISRCTN48334791). A&E, accident and emergency; AAA, abdominal aortic aneurysm; CT, computed tomography; eEVAR, emergency endovascular aneurysm repair.

Back to Article Outline

Discussion 

The evidence to support an EVAR-first approach for all patients with ruptured AAA is weak and largely drawn from three sources: results of single-center case series of EVAR for ruptured AAA, systematic reviews, and more recently, population-based studies arising from the United States.

Although encouraging mortality rates are published, significant biases exist. Reports from population-based studies may be misleading because they were unable to control for significant confounders of patient physiology and morphology. In addition, it is not known whether these studies are applicable outside the United States.

If EVAR can reduce the mortality rate of patients presenting to hospital with ruptured AAA, the management of ruptured AAA would have to change as well as the organization and delivery of emergency and vascular services. One consequence of such evidence might be to manage all ruptured AAA in large vascular centers because evidence already demonstrates that they operate on a higher proportion of patients with ruptured AAA and have better outcomes for all forms of aneurysm surgery.2 The evidence to underpin such changes must be scientifically and clinically robust.

In the United States there has been a steady yearly rise in the proportion of ruptured AAA treated by EVAR. In 2001, 6% of cases were performed by endovascular methods, rising to 19% by 2006.6 Why is EVAR playing an increasing role in the vascular surgeons' armamentarium? No doubt some surgeons are persuaded by the excellent outcomes reported from single-center experiences. Pioneering centers identified the prerequisites to provide an endovascular service for ruptured AAA patients.16 Most large units now have computed tomography (CT) scanners at or adjacent to the point of admission. Three-dimensional image reconstruction software is rapid and user friendly. The organization of an acute endovascular service has been facilitated by the introduction of dedicated protocols, availability of surgeons trained in endovascular techniques, and the use of hybrid operating theaters.17 Techniques have been developed for rapid deployment of aortic occlusion balloons and stent grafts to treat patients who are hypotensive or unstable. Stent graft technology has similarly improved immeasurably since the mid-1990s. Modular systems that can accommodate a large number of patients are available off the shelf in most hospitals.

However, there are genuine concerns about the widespread adoption of the endovascular technique. Data from United States indicate a disparity in the uptake and outcomes of EVAR between district and teaching hospitals.6 This may be partly explained by the high proportion of tertiary transfers of more stable referrals to teaching hospitals (up to one-third in some institutions).17 Patient selection biases nearly all of the published series.

Other fundamental and practical issues surrounding the technique remain unanswered in the current literature. First, outcomes of unstable patients in the endovascular groups may be prejudiced by an inherent delay for preoperative imaging. Second, anywhere between one-third and one-half of patients presenting with ruptured AAA may have an aneurysm that is morphologically unsuitable for EVAR. Finally, the endovascular technique itself imparts significant physiologic disturbance. Contrast and atheroemboli contribute to renal failure, and there are issues regarding the failure to seal the aneurysm (endoleak), the morbidity of reinterventions, and the development of abdominal compartment syndrome.

The only reasonable conclusion that can be drawn from the current literature is that the role of EVAR in the management of patients with ruptured AAA remains to be proven. Some patients appear to do very well after EVAR, but the paucity of quality data means that subgroup analysis to define optimal patient characteristics has been impossible. The outcome of EVAR in a nonselected patient population is unknown. One or more definitive randomized trials could provide the level I evidence to resolve these issues.

What attempts have been made to collect level I evidence? The Nottingham randomized trial was abandoned due to slow recruitment and an over-optimistic power calculation.1 Two further randomized studies have commenced, the AJAX and ECAR Trials. Both have been designed to recruit only the most stable patients, all of whom will be anatomically suitable for EVAR. These studies are easier to design, and they circumnavigate the ethical dilemmas arising as a result of randomizing cardiovascularly unstable patients. Randomization of patients after CT scanning misses the opportunity to define the role of an endovascular-first strategy vs open repair on an intention-to-treat basis.

The AJAX and ECAR trials may (or may not) show that EVAR is better for stable patients who have suitable aneurysm morphology. What evidence would be required to promote an EVAR first policy in “all-comers?” The United Kingdom Investigators of the IMPROVE trial believe such a trial would have to recruit and randomize patients at diagnosis, thus incorporating and analyzing the entire patient pathway, including any effects of patient transfer, emergency care, and imaging. Definitive trials also should incorporate protocols for best medical therapy (permissive hypotension/resuscitation) and must report the numbers and fates of patients excluded from the trials.

Back to Article Outline

References 

  1. Hinchliffe RJ, Bruijstens L, MacSweeney ST, Braithwaite BD. A randomised trial of endovascular and open surgery for ruptured abdominal aortic aneurysm - results of a pilot study and lessons learned for future studies. Eur J Vasc Endovasc Surg. 2006;32:506–513
  2. Egorova N, Giacovelli J, Greco G, Gelijns A, Kent CK, McKinsey JF. National outcomes for the treatment of ruptured abdominal aortic aneurysm: comparison of open versus endovascular repairs. J Vasc Surg. 2008;48:1092–1100
  3. Greco G, Egorova N, Anderson PL, Gelijns A, Moskowitz A, Nowygrod R, et al. Outcomes of endovascular treatment of ruptured abdominal aortic aneurysms. J Vasc Surg. 2006;43:453–459
  4. Lesperance K, Andersen C, Singh N, Starnes B, Martin MJ. Expanding use of emergency endovascular repair for ruptured abdominal aortic aneurysms: disparities in outcomes from a nationwide perspective. J Vasc Surg. 2008;47:1165–1170
  5. Giles KA, Pomposelli F, Hamdan A, Wyers M, Jhaveri A, Schermerhorn ML. Decrease in total aneurysm-related deaths in the era of endovascular aneurysm repair. J Vasc Surg. 2009;[Epub ahead of print]
  6. McPhee J, Eslami MH, Arous EJ, Messina LM, Schanzer A. Endovascular treatment of ruptured abdominal aortic aneurysms in the United States (2001-2006): a significant survival benefit over open repair is independently associated with increased institutional volume. J Vasc Surg. 2009;[Epub ahead of print]
  7. Vogel TR, Dombrovskiy V, Haser P, Graham A. Has the implementation of EVAR for ruptured AAA improved outcomes?. Vasc Endovasc Surg. 2009;[Epub ahead of print]
  8. Harkin DW, Dillon M, Blair PH, Ellis PK, Kee F. Endovascular ruptured abdominal aortic aneurysm repair (EVRAR): a systematic review. Eur J Vasc Endovasc Surg. 2007;34:673–681
  9. Visser JJ, van Sambeek MR, Hamza TH, Hunink MG, Bosch JL. Ruptured abdominal aortic aneurysms: endovascular repair versus open surgery–systematic review. Radiology. 2007;245:122–129
  10. Mastracci TM, Garrido-Olivares L, Cinà CS, Clase CM. Endovascular repair of ruptured abdominal aortic aneurysms: a systematic review and meta-analysis. J Vasc Surg. 2008;47:214–221
  11. Sadat U, Boyle JR, Walsh SR, Tang T, Varty K, Hayes PD. Endovascular vs open repair of acute abdominal aortic aneurysms–a systematic review and meta-analysis. J Vasc Surg. 2008;48:227–236
  12. Rayt HS, Sutton AJ, London NJ, Sayers RD, Bown MJ. A systematic review and meta-analysis of endovascular repair (EVAR) for ruptured abdominal aortic aneurysm. Eur J Vasc Endovasc Surg. 2008;36:536–544
  13. Azizzadeh A, Villa MA, Miller CC, Estrera AL, Coogan SM, Safi HJ. Endovascular repair of ruptured abdominal aortic aneurysms: systematic literature review. Vascular. 2008;16:219–224
  14. Nordon I, Hinchliffe RJ, Holt PJ, Morgan R, Loftus IM, Thompson MM. The role of emergency EVAR in the treatment of ruptured abdominal aortic aneurysms; a review. J Vasc Endovasc Surg. 2008;15:231–239
  15. Amsterdam Acute Aneurysm Trial Collaborators. Amsterdam acute aneurysm trial; background design and methods. Vascular. 2006;14:1–6
  16. Hinchliffe RJ, Braithwaite BD, Hopkinson BR. The endovascular management of ruptured abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2003;25:191–201
  17. Mehta M, Taggert J, Darling RC, Chang BB, Kreienberg PB, Paty PS, et al. Establishing a protocol for endovascular treatment of ruptured abdominal aortic aneurysms: outcomes of a prospective analysis. J Vasc Surg. 2006;44:1–8

 Competition of interest: none.

PII: S0741-5214(09)00237-7

doi:10.1016/j.jvs.2009.02.005

Journal of Vascular Surgery
Volume 49, Issue 4 , Pages 1077-1080, April 2009

Article Tools

* Image Usage & Resolution