The publication of the EndoVascular Aneurysm Repair (EVAR) 1 and 2 Trials and Dutch Randomised Endovascular Aneurysm Management (DREAM) Trial in June 2005 provoked intense interest from patients, the media and industry alike. Although the results were reported in some quarters as ‘conflicting’ which led to a confusing message to patients, the reality is that the EVAR and DREAM results are essentially the same.
Commenting on the significance of the EVAR Trials, Dr Frank Veith, Montefiore Medical Center, US, said, “The EVAR trials represent a truly remarkable achievement – probably the most important studies in the endovascular aneurysm field in the last decade. They will have great value to many all over the world for years to come.”
The results of the £1.7 million EVAR trials, commissioned by the NHS Health Technology Assessment (HTA) programme, in the UK, and published in The Lancet journal, consist of two separate randomised controlled trials for patients fit for open repair (EVAR 1) or unfit/high risk (EVAR 2). The trials recruited a total 1,420 patients making it the largest study of its kind globally. The multi-centred trials are run from Charing Cross Hospital, Hammersmith Hospitals NHS Trust, Imperial College London in collaboration with another 41 centres nationwide. After witnessing the EVAR presentation, Professor Peter Littlejohns, Medical Director of the National Institute Clinical Excellence (NICE) said that if scientific work was always of such high quality, NICE could disband.
EVAR 1 was first to compare EVAR and open repair (OR) and has been successful in recruiting a large number of patients (1,082) and experts to take part before the new EVAR technique became the first choice procedure of surgeons by default, making it of great interest to both the national and international medical communities.
The results were presented at an extra special meeting of the Endovascular Forum, at the Belfry, UK (under the auspices of The Vascular Society and The British Society of Interventional Radiology), and also at the Society for Vascular Surgery in Chicago, US. The significant 3% operative mortality benefit of EVAR over OR, shown in both EVAR I and DREAM in 2004, is maintained in terms of AAA related mortality, but lost in terms of all-cause mortality in this four year follow-up. However, EVAR is a developing technology and is associated with increased surveillance needs, NHS costs and the risk of further procedures, including conversion to OR.
In the high risk patients (people who were unfit for an OR) for whom EVAR was originally developed, there was no demonstrable benefit in terms of either mortality or quality of life, and 7% of patients died in the first 30 days after the elective operation.DREAM
DREAM confirmed a 3% operative mortality over OR in 2004 and then reported a two year follow up on 351 patients with AAA greater than 5.0cm in the New England Journal of Medicine a week earlier than the declared EVAR publication date. DREAM lead investigators, Professor Jan Blankensteijn, Professor of Vascular Surgery, Radboud University Medical Center Nijmegen, and Dr Monique Prinssen of the University Medical Center, Utrecht, the Netherland; declined joint publication and presentation at the Belfry with the EVAR trials.
On behalf of DREAM trialists, the lead applicants announced that at one and two year follow-up there was no significant difference in all course mortality and interpreted this that endovascular repair benefits are lost within a year.
Commenting on their findings, the DREAM research team said, “The survival advantage resulting from a less-invasive approach to aneurysm repair may largely be based on postponing death among higher-risk patients from the peri-operative period to the subsequent months. Another possible explanation for the convergence of survival curves is the failure of endovascular repair to prevent rupture of the aneurysm.”
Mid-term EVAR results provide food for thought
“The EVAR trial results will affect clinical practice at once,” said Professor Greenhalgh, lead applicant and chair of the Trial Management Committee. “There will be cautious enthusiasm for the use of EVAR in low risk patients but personally, I for one shall not offer EVAR in high risk patients.”
Professor Janet Powell, member of the Trial Management Committee, speaking about the EVAR 2 results, added, “If the patient is high risk, the emphasis should be to get the patient fit enough first rather than perform early EVAR.”
In EVAR 1, the 3% operative mortality benefit was maintained at four years in terms of AAA related mortality. The week after the release of DREAM results the sustained mid-term benefit of EVAR was confirmed. This put a completely different interpretation upon the DREAM message, which a week before had implied that all endovascular benefits were soon lost.
Even though DREAM reported on a smaller group with short follow-up, Professor Blankensteijn remarked that the DREAM data on AAA related mortality and all-cause mortality are exactly in line with the EVAR 1 sustained 3% benefit of EVAR.
Frank Lederle, Professor of Medicine at the Minneapolis VA Medical Center and trial coordinator of the US Open Versus Endovascular Repair (OVER) trial, commented in an article accompanying the publication of the DREAM trial results, “the primary endpoint of the DREAM trial was 30-day outcomes and it was not powered to assess long-term outcomes (with only 38 deaths overall).”
It has been suggested that some vascular surgeons will be disappointed with the results of EVAR 2 as it was felt that the minimally invasive approach might have a prominent role in patients not fit for conventional surgery. However, the EVAR 2 Trial will provide food for thought and help to inform the consent process, especially in high risk patients for whom the benefit of intervention for AAA seems far from clear. Drs J Earnshaw (Gloucestershire Vascular Group, Gloucestershire Royal Hospital, Gloucester, UK) and J A Murie (Vascular Surgery Service, Royal Infirmary of Edinburgh, UK) writing in the British Journal of Surgery (2005; 92: 925-927) commented that for fit patients, “EVAR will no doubt continue to be used, particularly if the cost can be reduced, but the trialists should be encouraged to continue close follow-up for several more years to ensure that the 3% advantage does not disappear. In the interim, patients, the media and the industry will no doubt drive EVAR forward; the minimally invasive nature of the procedure and the 3% improvement in early survival will be perceived as worthwhile.”
Certainly the influence and ramifications of the EVAR Trials cannot be overlooked. EVAR pioneer, Claude Mialhe, Clinique Notre Dame, Draguignan, France, said, “Currently reimbursement of EVAR in France is for high-risk patients only, which was decided by a so-called committee of experts. Following the outcomes obtained from the EVAR trials, the reimbursement policy needs to be turned on its head as level one evidence has demonstrated that the endovascular technique is safer than open repair in good risk patients and that endovascular repair is not effective in high risk ones.”
Dr Juan Parodi, the founding father of EVAR, said, “The EVAR trials are impeccable. As for EVAR 2, after 15 years of treating high risk patients with EVAR, I realised that a multi-disciplinary group to optimise clinical condition should be the priority before intervention. In addition, it is necessary to have a variety of devices to hand to achieve the best results. My learning curve over 15 years has indicated ever lower operative mortality and rupture rate approaching zero.”
However, regarding EVAR, the last word should go to Professor Greenhalgh, “When we first mentioned the trial in 1996, there were three possible outcomes regarding the trials; if open repair wins it will be the end of EVAR; if EVAR wins, there will be caution; and a draw would validate EVAR. These results validate the use of EVAR in fit patients. An important minority of patients are anatomically unsuited for EVAR in our current state of knowledge and therefore surgeons must still be trained to do open aneurysm repair. Vascular specialists of the future will need operative and catheter skills to be able to manage all problems.”