The vascular community is waiting with bated breath for the outcome of an evidenced-based review of endovascular aneurysm repair (EVAR), sponsored by the Agency for Healthcare, Research and Quality (AHRQ). The review is comparing open surgical repair to EVAR to determine the best practice for aortic abdominal aneurysms (AAAs) by assessing literature, clinical trial and registry data, and is due to be published by spring 2006.
“This upcoming evidence report will be a first step in closing the gaps in our knowledge of how to best treat AAAs,” said AHRQ director
Dr Carolyn M Clancy. “Most of the high-quality studies have been conducted in Europe and Australia and have focused mainly on white men. Additional research on how to diagnose and treat the condition in men of other races and in women, especially those with a positive family history or with risk factors for cardiovascular disease is needed. With steady increases in life expectancy and new approaches to treatment these are issues of great concern to physicians providing care to older Americans.”
Dr Gregorio Sicard, past-president of the Society for Vascular Surgery (SVS) and Chairman of the SVS Outcomes Committee, told Vascular News, said that there are growing fears that the AHRQ report will make similar recommendations to those recently been made in a Belgian Health and Technology Assessment (HTA) report that declared EVAR to be “a failed experiment” and advised against introduction of EVAR in routine healthcare.
“The Belgian document said that the devices were too expensive. It may be that the Centers for Medicare and Medicaid Services (CMS) reduces the costs by cutting back the payment to medical centers and physicians, thereby putting pressure on industry to lower costs. However, although there is competition in the market, the price for the stent grafts has actually increased. We do not know what the ramifications (of the AHRQ report) will be. Nobody knows.”
Sicard said, “The decision to begin the review was taken, in part, following the results of the UK’s EndoVascular Aneurysm Repair Trial 2 (EVAR 2) , which were a surprise to everyone as we thought that EVAR would be more beneficial in high-risk patients. If the EVAR 2 data had been more positive, my feeling is the AHRQ review would never have happened.”
EVAR Trial 2 was a multi-center, randomized controlled trial comparing EVAR with medical therapy against medical therapy alone for patients considered unfit for open repair (high-risk). The current interpretation of the trial showed that EVAR had a 7% 30-day operative mortality in these patients. At four years, EVAR did not improve longer-term survival and was associated with a need for continued surveillance and re-interventions, at substantially increased cost.
As a result of the AHRQ review and HTA report, the SVS Outcomes Committee decided to examine data in high-risk patients from the Lifeline Registry for Enodvascular Aneurysm Repair to see whether they could submit them to AHRQ. The Committee analysed data from the LifeLine Registry, which is Post Market Application data from company trials (Medtronic, Gore, EVT, Guidant and Endologix), to see how many patients fit the same criteria for high-risk patients described in EVAR trials. The analysis was not randomized and the centers were chosen for demonstrated excellence of both open and endovascular repair. The patients were originally randomized for endograft vs open repair in the US clinical trials, but this method of patient assignment to treatment arm was abandoned as patients were not willing to be offered a less invasive approach and then be randomized to surgery, with some institutional review boards deciding that randomization in their circumstances was unethical.
The Lifeline Registry was established in October 1998 and has developed various clinical and data collection protocols through the efforts of key experts and independent consultants to address the introduction of EVAR technologies. The registry was initiated through a collaboration involving clinical investigators, the medical device industry and representatives of both FDA and CMS. Two key organizations are the Lifeline Foundation of the SVS as the organizing body and source of clinical information, and NERI (New England Research Institutes, Inc.), which provided the registry data and statistical center.
Data in the Lifeline Registry is unique from several aspects and is not limited by the classical criticisms of “registries” in general. Data consists of high-compliance, mandatory data connection as part of the PMA approval process conducted by the FDA. The data is independently audited with source document verification with five year surveillance of the the patients be a condition of approval for sale of the approved commercial device. For this reason the Lifeline Registry is the sole source of independently audited, high-compliance surveillance information on device performance and exceeds the lower level observations that is the standard in most clinical studies, and certainly any voluntary registries.
The results showed from a cohort of over 3,000 patients that 539 were found to match the definition of high-risk in EVAR 2. These data revealed that were similar inclusion using criteria as in EVAR 2, mortality was around 2%.
The Outcomes Committee then examined the Lifeline Registry outcomes of high-risk patients. Subsequently, the SVS Outcomes Committee has received additional high-risk data from Cook and Endologix, which have been added to the 539 cohort of patients. Sicard predicted that the data, taken from an estimated 600-700 patients in total, would show a mortality rate similar to that seen in the cohort of the original 539 patients (around 2%).
The Committee is planning to publish its findings in time for the AHRQ to consider them. Sicard commented, “I don’t know what the AHRQ timetable is. We know it is at an advanced stage and we had heard that it would be published in March or April 2006.”
There are concerns that the recommendations of the AHRQ review could restrict the availability of EVAR for high-risk patients – the group that most interventionalists in the US feel receive the greatest benefit from this technology. It is hoped that the data from the SVS will provide an insight in terms of outcomes in high-risk patients as there are limitations regarding the evidence on which the Agency are basing their conclusions ie. literature and other registry data. “Whether the CMS will limit re-imbursement as a result [of the AHRQ report] remains to be seen as we do not know whether they have made a financial analysis,” Sicard added.
The debate surrounding high-risk patients in the EVAR 2 were discussed at the recent International Symposium on Endovascular Therapy. Dr Edward Diethrich, Phoenix, AZ, noted that the decision of whether a patient was unfit was taken at a local level. Professor Roger Greenhalgh, London, UK, responded by stating that an examination of patients’ characteristics in EVAR 2 (poor renal function, cardiovascular disease and other co-morbidities) revealed that, “the patient had one foot in the grave and the other on a bar of soap”.
At the time of going to press, the AHRQ has issued its evidence-based review and is waiting for submissions from industry and other interested parties.
Professor Roger Greenhalgh, Principal Investigator of the EVAR trials, commented that the EVAR 2 results surprised the EVAR trial management committee. “The statistical plan was determined before data were seen and when the results emerged, there was enormous surprise.
“The EVAR 2 trial is unique and unlikely to be repeated. Leastways there has been no enthusiasm to emulate it thus far. It was always claimed that it was unethical because it was obvious that EVAR would not be beneficial in these patients, they have large aneurysms and EVAR should reduce rupture rate and it simply did not in EVAR 2.”
Why not? Greenhalgh drew attention to the lower than expected rupture rate of aneurysms compared to the 50% mortality at two years from similar patients in the UK Small Aneurysm Trial. The anatomical suitability for EVAR itself seems to have conferred a lower rupture risk. “The devil is that the very patients anatomically suitable for EVAR need EVAR the least!
“Also, focus needs to move to improving fitness for intervention. The EVAR 2 data at least showed us that the 47 cross-over patients had a lower eventual mortality when they had an intervention that was delayed rather than a fast and ferocious EVAR ‘on the hoof’.”