Trial status

The recruitment phase of the trial was between 1 September 1999 and 31 August 2004. The 10-year follow-up closed in 2009 and results were published in 2010 and the long-term follow up to 15 years was completed in June 2015.  

Trial documents

Original protocol - EVAR Trial
Final protocol - EVAR Trial
Statistical analysis plan - EVAR Trials 10-15 year follow-up

Trial design

The UK EVAR Trials comprise of 2 multicentre randomised controlled trials to assess the role of EndoVascular Aneurysm Repair (EVAR) in the treatment of large Abdominal Aortic Aneurysm (AAA). Patients of both sexes aged at least 60 years with an AAA measuring 5.5cm or greater according to Computed Tomography (CT) scan were assessed for anatomical suitability for EVAR. Suitable patients were offered entry into EVAR Trial 1 if they were considered fit enough to have open AAA repair and consenting patients were randomised to receive either EVAR or open repair. Patients who were considered unfit for open repair were offered entry into EVAR Trial 2 which randomised patients between EVAR with medical therapy against no intervention with medical therapy. All patients are followed up for death through the Office for National Statistics (ONS) and an endpoints committee reviews the causes of death to ascertain aneurysm-related mortality. Local coordinators at each of the 41 participating hospitals are responsible for collection of data on the primary AAA repairs as well as Health Related Quality of Life (HRQL), adverse events, graft related complications and re-interventions.

Results for 30-day operative mortality in EVAR Trial 1 were published in August 2004. After publication of these results, 26/37 centres remained in equipoise and continued recruitment into a separate study from 1st September 2004 until 15th June 2005 when primary outcome results (mortality after a minimum of 1 year after randomisation follow up) were published. Publication of these mid-term results included results for all-cause mortality, AAA-related mortality, quality of life, complications, re-interventions and costs. Results to 10 years of follow up (median 6 years) for all-cause mortality, AAA-related mortality, complications, re-interventions and costs were published in 2010. Other research has been published on the impact of fitness in EVAR Trial 1, a comparison of EVAR devices for both trials, a cost effectiveness model for EVAR 1, an analysis of factors associated with AAA rupture in EVAR 2 and the impact of the different AAA management strategies on renal function and cardiovascular event rates.

Summary of results for EVAR trial 1 to 2009

Between September 1999 and August 2004, a total of 1252 patients were randomised (626 to EVAR) across 38 UK hospitals. The operative mortality results were published in 2004 and demonstrated that EVAR was associated with a 3-fold reduction in operative mortality when compared to open repair. Mid-term results to 4 years showed that this early operative mortality benefit was sustained in terms of AAA-related mortality but no difference in all-cause mortality was seen between the groups. In addition, the operative mortality advantage seen with EVAR was accompanied by an improvement in quality of life during the first 3 post operative months. However, these benefits were offset by a continued need for surveillance and an increased rate of complications and re-interventions which contributed to an overall increase in cost and possibly eroded the early quality of life benefit, when compared to open repair.

Summary of results for EVAR trial 2 to 2009

Between September 1999 and August 2004, a total of 404 patients were randomised (197 to EVAR) across 31 UK hospitals. The mid-term results to 4 years were published in June 2005 and were more controversial than those published for EVAR Trial 1. It had been expected that the use of EVAR would decrease overall mortality by reducing the number of deaths from aneurysm rupture but the mid-term results showed that EVAR conferred no benefit over medical therapy alone in terms of all-cause mortality, AAA-related mortality or quality of life and was associated with an increased incidence of complications and need for re-interventions contributing to a much greater cost. Factors that contributed to this lack of benefit were the 9% operative mortality in the EVAR group which was higher than we had anticipated and the rupture rate of just 9 per 100 person years in the no intervention group which was lower than the rupture rates published in similar cohorts in the literature.

One of the clearest messages to emerge was that this cohort of unfit patients were particularly unwell and died at a very high rate (65% dead within 4 years) but more importantly they appeared to be dying predominantly of other co-morbidities rather than their aneurysm. Furthermore, a per protocol analysis of those complying with their randomised allocation demonstrated similar results to the intention-to-treat analyses. Our concluding message was that clinicians should concentrate on improving general fitness in these patients rather than rushing to perform EVAR. Subsequent analysis of factors associated with aneurysm rupture in these unfit patients with large aneurysm has provided some evidence that anatomical suitability for EVAR may confer some reduction in risk of rupture. Further evidence has emerged of a possible reduction in rupture rate for those patients taking statins but this requires confirmation in a prospective randomised controlled trial.

Long term extension to 15 years

From the beginning, the purpose of this trial was to compare endovascular and open repair for elective AAA, with the proviso that should there be concerns about the durability of EVAR the trial would be extended. After publication of the results to September 2009, further analysis showed that secondary sac rupture after EVAR, associated with 67% mortality, was an emerging concern adding to late aneurysm-related mortality. With this in mind, further funding was sought for the very long-term comparison of aneurysm-related mortality (as well as total mortality), the funding finally being obtained in 2012, for follow-up to 2015. Ethical approval for this continued follow-up was granted in February 2011. Patients were followed up until 30th June 2015 for mortality using record linkage from the Office of National Statistics as before, as well as re-interventions. The health economists also planned a very long-term cost-effectiveness evaluation based on these new data.

In 2012-13, it became clear that many patients were no longer under regular follow up at the original trial hospitals. In order to obtain missing information about patient hospital visits during this phase of follow-up, in February 2015 we were granted approval to obtain data on hospital admissions and procedures from a government database which stores information about all patient hospital visits in England. In June 2015, data were obtained for patients who were participants in the EVAR 1 trial at hospitals in England and who had been lost to aneurysm related follow-up. These confidential data are known as Hospital Episode Statistics (HES) data. We interviewed (face-to-face) trial participants coming for routine hospital visits. We asked them if they would be happy for us to access confidential data from NHS and government records. All interviewed patients stated that they would be happy for us to access information in this way. These records have allowed us to complete our comparison of open repair versus endovascular repair up to 15 years after randomisation. Only the researchers involved in the study have access to the HES data and no information relating to individual patients will ever be identified in any publications or other outputs. We obtained information about hospital admissions (including dates, reason for admission and any procedures or operations performed) from 1st September 2009 to 31st March 2015. We have used these data to allow us to identify aneurysm-related re-interventions for English patients. Follow up was better in the Scottish and Northern Ireland centres, so that administrative data were not sought for their patients.

Summary of results for EVAR trial 1 to 2015

Previous reports for the EVAR 1 trial have demonstrated that 0-6 months after randomisation, patients in the EVAR group had a lower overall mortality and aneurysm-related mortality. Four years after randomisation, there was a persistent reduction in aneurysm-related deaths in the EVAR group but overall mortality was similar in the two groups. The longer term results up to 15 years show that beyond 8-years of follow-up, open repair has a significantly lower overall mortality and aneurysm-related mortality. The increased aneurysm-related mortality in the EVAR group after 8 years was mainly attributable to secondary aneurysm sac rupture with increased cancer mortality also observed in the EVAR group. Endovascular repair was also associated with increased rates of graft-related re-interventions throughout the trial.  In conclusion, EVAR has an early survival benefit but an inferior late survival compared with open repair, which needs to be addressed by lifelong surveillance of EVAR and re-intervention if necessary.    

Research collaborators

• Professor SG Thompson (Cambridge) - Statistics (to 2010)
• Dr Michael Sweeting (Cambridge) - Statistics (2011 - 2016)
• Professor MJ Sculpher (York) – Health Economics
• Dr David Epstein (York and Granada (Spain) - Health Economics

Participants 

Grant applicants (1999-2009)
Professor RM Greenhalgh (lead applicant), Professor DJ Allison, Professor PRF Bell, Professor MJ Buxton, Mr PL Harris, Professor BR Hopkinson, Professor JT Powell, Professor IT Russell, Professor SG Thompson.

Grant applicants for late follow-up (2011 - 2016)
Professor RM Greenhalgh (lead applicant), Professor JT Powell, Dr MJ Sweeting, Professor M Sculpher, Dr D Epstein, Mr CD Bicknell

Trial Management Committee (2011 - 2016)
Professor Roger Greenhalgh (Chairman), Professor Janet Powell, Michael Sweeting (Statistics), David Epstein (Health Economics), Colin Bicknell (Vascular Surgeon), Regula Von-Allen (Vascular Surgeon), Thomas Wyss (Core Laboratory), Nick Burfitt (Radiologist BSIR)

Trial Steering Committee (2011 - 2016)
Professor Richard Lilford (Chairman), Professor Roger Greenhalgh (TMC), Mr Michael Wyatt (Newcastle), Professor Simon Thompson (Statistics), Professor Mark Sculpher (Health Economics)

Data Monitoring & Ethical Committee (2011 - 2016)
Professor Gerry Fowkes (Chair), Dr Robert Morgan (BSIR), Professor Bruce Campbell (Vascular Surgeon & NICE)

Endpoints Committee
Professor Janet Powell, Professor Alison Halliday (Vascular Surgeon & Trialist, Oxford), Dr Simon Gibbs (Cardiologist, Imperial)

Regional Trial Investigators Committee

Numbers in parentheses indicate the number of patients entered into both the EVAR 1 and EVAR 2 trials:

K. Varty, C. Cousins, Addenbrookes Hospital, Cambridge (10); D. Harkin (2010-2015), R.J. Hannon, L. Johnston, Belfast City Hospital, Belfast (53); A.W. Bradbury, M.J. Henderson, Birmingham Heartlands Hospital, Birmingham (8); D. Ritoo (2010-2015), S.D. Parvin, D.F.C. Shepherd, Bournemouth General Hospital, Bournemouth (68); C. Bicknell (2010-2015), R.M. Greenhalgh, A.W. Mitchell, Charing Cross Hospital, London (27); S. Dimitri (2010-2015), P.R. Edwards, G.T. Abbott, Countess of Chester Hospital, Chester (15); D.J. Higman, A. Vohra, University Hospital Coventry, Coventry (8); S. Ashley, C. Robottom, Derriford Hospital, Plymouth (2); M.G. Wyatt, J.D.G. Rose, Freeman Hospital, Newcastle (121); K. Daly (2010-2015), D. Byrne, R. Edwards, Gartnavel General Hospital, Glasgow (12); K. Daly (2010-2015), D.P. Leiberman, D.H. McCarter, Glasgow Royal Infirmary, Glasgow (19); B. Modarai (2010-2015), P.R. Taylor, J.F. Reidy, Guy’s and St. Thomas’ Hospital, London (124); P. McCollum (2010-2015), A.R. Wilkinson, D.F. Ettles, Hull Royal Infirmary, Hull (29); I. Nichol (2010-2015), A.E. Clason, G.L.S. Leen, James Cook University Hospital, Middlesborough (19); N.V. Wilson, M. Downes, Kent and Canterbury Hospital, Canterbury (1); J. Abraham (2010-2015), S.R. Walker, J.M. Lavelle, Lancaster General Infirmary, Lancaster (12); M.J. Gough, S. McPherson, Leeds General Infirmary, Leeds (38); D.J.A. Scott, D.O. Kessell, Leeds St. James’s Hospital, Leeds (11); R. Naylor, R. Sayers, N.G. Fishwick, Leicester Royal Infirmary, Leicester (148); S. Vallabhaneni (2010-2015), P.L. Harris, D.A. Gould, Liverpool Royal Hospital, Liverpool (143); J.V. Smyth (2010-2015), M.G. Walker, N.C. Chalmers, Manchester Royal Infirmary, Manchester (96); A. Garnham, M.A. Collins, New Cross Hospital, Wolverhampton (1); S. Thomas (2010-2015), J.D. Beard, P.A. Gaines, Northern General Hospital, Sheffield (77); M.Y. Ashour, R. Uberoi, Queen Elizabeth Hospital, Gateshead (18); S. Macsweeney (2010-2015), B. Braithwaite, S.C. Whitaker, Queen’s Medical Centre, Nottingham (116); J.N. Davies, S. Travis, Royal Cornwall Hospital, Truro (26); M. Davis (2010-2015), G. Hamilton, A. Platts, Royal Free Hospital, London (42); A. Shandall, B.A. Sullivan, Royal Gwent Hospital, Newport (1); S. Sarkar (2010-2015), M. Sobeh, M. Matson, Royal London Hospital, London (7); A.D. Fox, R. Orme, Royal Shrewsbury Hospital, Shrewsbury (7); W. Yusef, T. Doyle, Royal Sussex County Hospital, Brighton (6); J. Budd (2010-2015), M. Horrocks, J. Hardman, Royal United Hospital, Bath (34); D. Harkin (2010-2015), P.H.B. Blair, P.K. Ellis, Royal Victoria Hospital, Belfast (46); G. Morris, A. Odurny, Southampton General Hospital, Southampton (39); A. Tiwari (2010-2015), R. Vohra, M. Duddy, Selly Oak Hospital, Birmingham (22); M. Thompson, T.M.L. Loosemore, A.M. Belli, R. Morgan, St. George’s Hospital, London (54); O. Agu (2010-2015), M. Adiseshiah, J.A.S. Brookes, University College Hospital, London (69); C.N. McCollum, R. Ashleigh, University Hospital of South Manchester, Manchester (127);

Trial Coordinators: M. Aukett, C. Bailey (2010-2015), S. Baker, E. Barbe, G. Bate (2010-2015), N. Batson, J. Bell, J. Blundell, D. Boardley, S. Boyes, H. Brooks (2010-2015), O. Brown, J. Bryce, J. Burrough (2010-2015), M. Carmichael, T. Chance, S. Clarke (2010-2015), J. Coleman, C. Cosgrove, G. Curran, L. Dabee (2010-2015), L. Dali-Kemmery (2010-2015), A. Datson (2010-2015), M. Davis (2010-2015), T. Dennison, C. Devine, N. Dewhirst, B. Errington, H. Fairey (2010-2015), H. Farrell, C. Fisher, P. Fulford, M. Gough, C. Graham, C. Harrison (2010-2015), R. Hooper, G. Horne, L. Horrocks, B. Hughes, T. Hutchings, M. Ireland, C. Judge, L. Kelly, J. Kemp, A. Kite, M. Kivela, M. Lapworth, C. Lee, L. Linekar, A. Mahmood, L. March, J. Martin, N. Matharu, K. McGuigen, P. Morris-Vincent, S. Murray, A. Murtagh, J. Myerscough (2010-2015), G. Owen, V. Ramoutar, C. Rippin, J. Rowley, L. Sequeira (2010-2015), J. Sinclair, S. Spencer, V. Taylor, H. Thompson (2010-2015), C. Tomlinson, S. Ward, V. Wealleans, J. West, K. White, J. Williams, L. Wilson, A. Wye (2010-2015).

Publications

1. Brown LC, Epstein D, Manca A, Beard JD, Powell JT, Greenhalgh RM. The UK Endovascular Aneurysm Repair (EVAR) trials: design, methodology and progress. Eur J Vasc Endovasc Surg 2004; 27(4):372-381.
2. EVAR Trial Participants. Comparison of endovascular aneurysm repair with open repair in patients with abdominal aortic aneurysm (EVAR trial 1), 30-day operative mortality results: randomised controlled trial. Lancet 2004; 364(9437):843-848.
3. EVAR Trial Participants. Endovascular aneurysm repair versus open repair in patients with abdominal aortic aneurysm (EVAR trial 1): randomised controlled trial. Lancet 2005; 365(9478):2179-2186.
4. EVAR Trial Participants. Endovascular aneurysm repair and outcome in patients unfit for open repair of abdominal aortic aneurysm (EVAR trial 2): randomised controlled trial. Lancet 2005; 365(9478):2187-2192.
5. Greenhalgh RM, Brown LC, Powell JT. High risk and unfit for open repair are not the same. Eur J Vasc Endovasc Surg 2007; 34(2):154-155.
6. Brown LC, Greenhalgh RM, Howell S, Powell JT, Thompson SG. Patient fitness and survival after abdominal aortic aneurysm repair in patients from the UK EVAR trials. Br J Surg 2007; 94(6):709-716.
7. Brown LC, Greenhalgh RM, Kwong GP, Powell JT, Thompson SG, Wyatt MG. Secondary interventions and mortality following endovascular aortic aneurysm repair: device-specific results from the UK EVAR trials. Eur J Vasc Endovasc Surg 2007; 34(3):281-290.
8. Powell JT, Brown LC, Greenhalgh RM, Thompson SG. The rupture rate of large abdominal aortic aneurysms: is this modified by anatomical suitability for endovascular repair? Ann Surg 2008; 247(1):173-179.
9. Epstein DM, Sculpher MJ, Manca A, Michaels J, Thompson SG, Brown LC et al. Modelling the long-term cost-effectiveness of endovascular or open repair for abdominal aortic aneurysm. Br J Surg 2008; 95(2):183-190.
10. Rodway AD, Powell JT, Brown LC, Greenhalgh RM. Do abdominal aortic aneurysm necks increase in size faster after endovascular than open repair? Eur J Vasc Endovasc Surg 2008; 35(6):685-693.
11. Brown LC, Brown EA, Greenhalgh RM, Powell JT, Thompson SG, on behalf of the UK EVAR Trial Participants. Renal function and abdominal aortic aneurysm: the impact of different management strategies on long-term renal function in the UK EndoVascular Aneurysm Repair (EVAR) Trials. Ann Surg 2010; 251:966-975.
12. Brown LC, Greenhalgh RM, Thompson SG, Powell JT. Does EVAR Alter the Rate of Cardiovascular Events in Patients with Abdominal Aortic Aneurysm Considered Unfit for Open Repair? Results from the Randomised EVAR Trial 2. Eur J Vasc Endovasc Surg 2010; 39(2).
13. Brown LC, Greenhalgh RM, Powell JT, Thompson SG. Use of baseline factors to predict complications and reinterventions after endovascular repair of abdominal aortic aneurysm. Br J Surg 2010; 97(8):1207-1217.
14. The UK EVAR Trial Investigators. Endovascular repair of aortic aneurysm in patients physically ineligible for open repair. N Engl J Med 2010; 362(20):1872-1880.
15. The UK EVAR Trial Investigators. Endovascular versus open repair of abdominal aortic aneurysm. N Engl J Med 2010; 362(20):1863-1871.
16. Wyss TR, Brown LC, Powell JT, Greenhalgh RM. Rate and predictability of graft rupture after endovascular and open abdominal aortic aneurysm repair: data from the EVAR Trials. Ann Surg 2010; 252(5):805-812.
17. Brown LC, Thompson SG, Greenhalgh RM, Powell JT, on behalf of the EVAR Trial Participants. Incidence of cardiovascular events and death after open or endovascular repair of abdominal aortic aneurysm: results from the randomised EVAR Trial 1. Br J Surg 2011; published on line April 2011
18. Patel R, Sweeting MJ, Powell JT, Greenhalgh RM for the EVAR trial investigators. Endovascular versus open repair of abdominal aortic aneurysmin 15-years' follow-up of the UK endovascular aneurysm repair trial 1 (EVAR trial 1): a randomised controlled trial. Lancet 2016; 388: 2366-74