MDNM: DESCRIBE THE NICE UK GUIDELINE AND WHEN THE STUDY COMMENCED?
DR. SULTAN: The NICE UK guideline is a data synthesis, which is substantially based on a published Cochrane review from 2014. This review was then updated by the NICE committee in consultation with the Cochrane Vascular group in 2017. The original 2014 study by Paravastu et al included 4 randomized controlled trials which recruited patients between 1999 and 2004. The trials included are EVAR-1 (U.K.), DREAM (The Netherlands), ACE (France) and OVER (USA). The 2017 updated review did not find any additional trials but did identify more updated publications from the original trial groups (EVAR 1 and DREAM). The total number of patients included in this data synthesis is 2,783, 94% of which are male.
In their review of complex EVAR, only one study was included. This was a study by Donas et al, published in 2012, which reviewed the 30-day outcomes of included 90 patients with juxtarenal AAA. These patients were treated with either chimney-EVAR (n=30), fenestrated-EVAR (n=29) or open surgical repair (n=31). This was a single center, non-randomized study.
MDNM: WHERE AND HOW WAS THE DATA COLLECTED?
DR. SULTAN: The NICE committee based their recommendations about standard EVAR on a meta-analysis of four randomized controlled trials. Therefore, the collated data is subject to the same limitations as the original trials from which it arose. For example, the EVAR-1 trial has been extensively criticized for trial methodological flaws such as cross-over between treatment arms. The data also needs to be contextualized because of the immaturity of operators and devices. The trials were undertaken from 1999 to 2004 when EVAR was in its relative infancy and learning curves had not been overcome.
With respect to the complex EVAR group, there was only one study which met the inclusion criteria of the review committee. This was a single-center, non-randomized trial of 90 patients with juxtarenal AAA, whose outcome were only reported at 30days. The mortality rate in this single study for patients treated by endovascular means was 0% compared to 6.4% (n=2) for the open repair group. There were two renal artery occlusions after endovascular repair, both of which were treated by iliaco-renal bypass. Although the authors of this study conclude that “Endovascular treatment of JAAA is a safe alternative for the short-term management of JAAA”, the NICE committee did not interpret the data favorably. Either way this is a single center study from a high-volume center, and as such is not globally applicable and certainly not robust enough to base national guidelines upon.
MDNM: IS THEIR ENOUGH IMPRESSIVE DATA IN THE GUIDELINES?
DR. SULTAN: Randomized controlled trials and meta-analysis are level 1 evidence. However, the data is restricted by the timing of the studies and the inherent limitations of RCTs that make them difficult to apply to real-world practice.
In terms of complex EVAR, these cases should only be performed in high-volume centers, and although the study by Donas et al represents such a center, a single center, non-randomized study does not provide a firm basis on which to determine international guidelines or standards of practice. The NICE committee did not explicitly recommend against the use of complex EVAR but they did specify that they should only be performed within the remit of a RCT. The futility of this is that those requiring complex EVAR are often not physically robust enough for open repair and in many cases true equipoise those not exist and thus randomization is impossible.
MDNM: WHO ARE THE PRINCIPAL INVESTIGATORS OF THE STUDY?
DR. SULTAN: NICE committees are made up of a diverse range of members including people who use health and social care services, careers and experts in health and social care.
The committee is chaired by Andrew Bradbury, Professor of Vascular Surgery at the University of Birmingham and it includes two other vascular surgeons, a radiologist, radiographer, theatre nurse, anesthetist, emergency department doctor, vascular scientist, vascular nurse and two lay members.
MDNM: WHEN WILL THE NICE UK GUIDELINES BE PUBLISHED?
DR. SULTAN: The draft guidelines for NICE have been circulated for consultation. It is due to be published in November 2018.
MDNM: IN YOUR OPINION, DO YOU THINK THIS STUDY IS INFLUENTIAL ENOUGH THAT IT WILL IMPACT EVAR GLOBALLY?
DR. SULTAN: NICE guidelines are an important factor in healthcare delivery in England but their impact on other countries and healthcare systems remains to be seen. The committee’s recommendations are largely based on economic parameters, all of which have been analyzed and presented only in the context of the UK National Health Service. The economic models of healthcare delivery vary greatly though the world and so this report is not ubiquitous or universally applicable.
One has to bear in mind that the committee is basing their recommendations on the long-term follow-up of old data. They concede that the outcomes of EVAR in terms of mortality are superior for open repair in the peri-operative period and remain equivalent up to 8 years. Beyond this open repair has demonstrated superiority. However, the window from 8 years to 15 years is based on very few patients and therefore not statically powered.
The other issue the committee has is with re-intervention, which in the RCTs they analyzed is double that of open repair. However again this is based on older generation grafts, which were implanted by inexperienced operators. It is also worth considering a lack of reporting of re-interventions for open repair, rather than a lack of occurrence of the need for re-intervention with open repair. Although the committee concede that this is old data, they state that they found no evidence that newer devices perform better than their earlier counterparts and did not consider this to be a reason to reject the evidence reviewed. What this amounts to is a recommendation based on “no evidence”. Surely that is not robust.
MDNM: WILL THE STUDY PROMPT OTHERS TO FOLLOW SUIT, IN PARTICULAR IN HIGH-VOLUME INSTITUTIONS?
DR. SULTAN: I think that the committee’s recommendations actually give credence to the use of complex EVAR, albeit within an RCT. However, they only recommend the investigation on complex EVAR in patient who are suitable for open repair and NOT in patients who are unsuitable for open repair. In fact, the only research recommendation that is provided in the document is “What is the effectiveness and cost-effectiveness of complex EVAR versus open surgical repair in people with an unruptured AAA for whom open surgical repair is a suitable option?” However, if such research is to be undertaken then the structure of such trials will be difficult and should certainly not take place outside of high–volume centers.
MDNM: ANY NEW EVIDENCE?
DR. SULTAN: No, I see a biased analysis of existing evidence. The only new evidence in the NICE document is the use of a “new model” for economics analysis which is not validated outside of this report and which pertains only to the UK. The delivery of vascular services within the UK, particularly the combined use of vascular surgery and radiology staff in aortic repair cases, is not a model which is used in the majority of countries.
The interpretation of the evidence was undertaken by a committee of three vascular surgeons and one radiologist and although one has to respect the professional integrity of the vascular surgeons involved, there is no doubt that unconscious bias may have been influential in this committee’s output. The aortic practices of those involved, i.e., whether mostly open or endovascular, should be made transparent, so that we can get a better understanding of how their conclusions were drawn.
MDNM: OTHER PEER-REVIEWED PUBLICATIONS, SUCH AS THE JOURNAL OF VASCULAR SURGERY, JOURNAL OF ENDOVASCULAR THERAPY AND SIMILAR PUBLICATIONS IN EUROPE THAT DOCUMENT ENOUGH DATA TO SUPPORT THE VALUE OF EVAR, ESPECIALLY FOR PATIENTS WHO PRESENT WITH CO-MORBIDITIES AND ARE ANATOMICALLY AT HIGH RISK. DO YOU AGREE?
DR. SULTAN: Absolutely, I agree. The crux of aortic treatment is its provision within high-volume centers, by operators who are equally proficient with open and endovascular repair and who understand and are experienced in deciphering which treatment applies best to each patient. This is about a personalized, patient-centered approach to optimal therapy.
MDNM: VASCULAR SPECIALISTS LISTEN TO EXPERTS RENDER THEIR OPINIONS AS IT RELATES TO OPEN SURGERY VS. EVAR AT VARIOUS CONTIUNING MEDICAL EDUCATION ACTIVITIES. IS IT FAIR TO SAY THAT ONE APPROACH IS BETTER THAN THE OTHER?
DR. SULTAN: EVAR and open repair are not competitive therapies, each have their own merits and the secret to aortic therapy, is the ability to decide which one to use and when.
There are a few other points worth considering.
Patients who are unsuitable for open repair are not afforded any chance of intervention by the NICE committee. This is largely due to economic reasons and is based on the poorly run EVAR 2 trial. Although they say they had re-evaluated the EVAR -2 data using a rank-preserving structural failure time (RPSFT) statistic to account for cross-over between treatment groups, they also recognised that, while plausible, the assumptions underpinning the RPSFT cannot be empirically validated.
- The evidence is not concrete and in fact the terms “low”, “very low” and “moderate” are used a lot to describe the quality of the evidence, while the term “high” is used less frequently. When the evidence is not black and white then the interpretation of that evidence is more difficult and more likely to be influenced by the underlying bias of the committee. This is a huge factor in the recommendations put forward in this document.
- The economics evidence in this document does not extend beyond the UK and the committee actively excluded documents that were based on other healthcare systems. The provision of EVAR in the UK is very different to other countries, in that two clinical teams are required per patient. Recommendations to reassess the costs around service provision, including medical teams, devices costs and surveillance programme efficiencies were not addressed, yet surely these are all areas in which savings can be made, which could easily tip the balance in terms of economic viability.
MDNM ASKED DR. FRANK J. VEITH, PROFESSOR OF SURGERY, NEW YORK UNIVERSITY MEDICAL CENTER (LANGONE HEALTH), NEW YORK, NEW YORK AND CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY, CLEVELAND, OH TO RENDER HIS OPINION.
DR. VEITH: Any negative impressions of EVAR for AAA treatment created by the NICE UK study are, in my opinion, misleading. EVAR is clearly a superior treatment to Open Repair (OR) for most AAAs – if it can be safely and effectively performed. Such safe effective treatment depends on the patient’s anatomy and the skills of the person performing the procedure. This is particularly true with the treatment of complex AAAs requiring Fenestrated EVAR (FEVAR) or Chimney EVAR (ChEVAR). All surgeons are not created equal, and some of the poor results with these latter procedures are due to their use by less experienced surgeons or in inappropriate patients. This should not negate the superiority of EVAR over OR in most patients. However, there are still some AAA patients who are better treated by OR. The problem today is that fewer vascular surgeons are being well trained in the difficult open procedures that are required in patients with complex juxta and pararenal AAAs. Such patients are probably best treated in specialized centers with appropriate experience in endovascular and open techniques for treating such AAAs. All these and other related topics will be thoroughly discussed at our 2018 VEITHsymposium in New York from November 13-17th.