The Steering Outcomes Committee of the Society for Vascular Surgery (SVS) has urged the Agency for Healthcare, Research and Quality (AHRQ) to examine data from the Lifeline Registry as part of its review to determine best practice for abdominal aortic aneurysms (AAAs). The conclusions from the Registry, to be published shortly in the Journal of Vascular Surgery, state that endovascular aneurysm repair (EVAR) in high-risk patients enrolled in United States Investigational Device Exemption (IDE) trials is safe and effective, with results superior to those of the EVAR 2 trial
As previously reported in Vascular News, the AHRQ review is attempting to determine best practice for AAA repair by comparing open surgical repair to EVAR in the literature and from clinical trial and registry data. It is due to be published imminently. There are concerns that the AHRQ’s recommendations could change Centers of Medicare and Medicaid Services coverage, thereby jeopardizing reimbursement of EVAR in high-risk patients, who represent approximately 70% of the market in the US. The SVS has expressed reservations concerning the level of evidence gathered by the Agency and has appealed to AHRQ to consider data from the Lifeline Registry before submitting its final report.
Vascular News spoke to Dr Rodney White, a member of the SVS Outcomes Committee: “The AHRQ report regarding EVAR is based on data that are available from sources that do not reflect the US experience with endografts in high-risk patients. It is very difficult to find peer-reviewed medical literature (level 1 evidence) that reflect what clinical practice ought to be.”
The Outcomes Committee believes such evidence can be found from the Lifeline Registry, which contains post-market application data from company trials (Medtronic, Gore, Cook, Guidant and Endologix). These can be used to determine short-term and four-year outcome measures of EVAR in equivalent high-surgical-risk patients in the US, using the most accurate and detailed data available, and to compare that with open surgery in light of the natural history of untreated AAAs and the EVAR 2 trial.
EVAR 2 was a multi-center, randomized controlled trial comparing EVAR plus medical therapy against medical therapy alone for patients considered unfit for open repair (high-risk). The current interpretation of the trial shows that EVAR had a 9% 30-day operative mortality in these patients. At four years, EVAR did not improve longer-term survival and was associated with a greater need for continued surveillance and re-intervention, at substantially increased cost.
To match the EVAR 2 definition of high risk, Lifeline Registry entrants were restricted to those older than 60 years, with a pre-procedure aneurysm diameter of more than 5.5cm and at least one co-morbidity (eg symptomatic congestive heart failure, valvular heart disease, cardiac arrhythmia, chronic obstructive pulmonary disease and chronic renal failure). The pooled data from five US IDE trials contained 2,558 patients. Selection criteria (between EVAR and open repair) in these series were comparable, as reflected by the instructions for use of the devices. Of these, 565 EVAR patients and 61 open repair patients met this definition of high-risk. The remaining 1,651 EVAR and 281 open repair patients were considered normal risk.
Results from the Lifeline dataset revealed a 30-day operative mortality rate for EVAR in this high-risk patient cohort of 2.9% compared to 5.1% for open repair. There was one AAA-related death in the interval from 30 days to one year in the EVAR group and none in open. The AAA-related death rate at one year was 3.0% for EVAR and 5.1% for open. Four additional AAA-related deaths occurred in the EVAR group, thus freedom from AAA-related death after EVAR was 97% at 30 days and 96% at four years by Kaplan-Meier analysis. After open repair, freedom from AAA-related death was 95% at 30 days and remained at that level to four years.
The study found there was no significant difference in all-cause mortality between EVAR and open repair through the duration of this analysis. Four-year survival was 56% in EVAR and 66% in open repair. All-cause mortality at four years in the high-risk IDE patients was also compared with the normal-risk IDE patients. The high-risk EVAR mortality was twice that of the non-high-risk patients (44% vs 21%).
The Outcomes Committee report states therefore that despite fitting the EVAR 2 definition of high risk, US IDE mortality rates compare favorably with EVAR 2 in the short term (30-day mortality: 2.9% IDE, 9% EVAR 2) and at four years (44% IDE, 64% EVAR 2). “We believe the US IDE results indicate that EVAR is safe and effective in most patients with advanced age, large aneurysms, and high-risk medical comorbidities,” the report states.
White added: “This is probably the highest-level evidence in terms of reliability we have. It is not level 1 randomized evidence, but it went to the FDA, and it is chart reviewed, which means every patient’s data have been verified back to the chart, which never happens in a randomized trial. Using the same definitions (as EVAR 2) the Lifeline data reported a 2.9% 30-day morbidity/mortality rate. This is acceptable to us, acceptable to patients – acceptable across the whole board.”
Disparities between EVAR 2 and Lifeline
So why are there differences between the EVAR 2 trial results and those of the Lifeline Registry? According to the study, there are at least two identifiable explanations for the large outcomes differences between the high-risk patients in the IDE trials and those in EVAR 2. Firstly, since a total of 14 patients in EVAR 2 died pre-operatively during the 57-day interval between randomization and repair, the study claims therefore that 52% of the perioperative deaths (14/27) and 19% of total deaths in the EVAR arm occurred pre-operatively. Nine patients died from AAA rupture before their elective EVAR date, accounting for 45% of the 20 aneurysm-related deaths in the EVAR arm of EVAR 2. Many of these deaths might not have occurred with a shorter interval before repair.
Secondly, the final decision to include a patient in EVAR 2 was delegated to the individual providers at each hospital (eg surgeon, radiologist, anesthesiologist and cardiologist) under a ‘pragmatism’ guideline. Therefore, not only was it necessary for a patient to meet one of the cardiac, pulmonary or renal criteria, but the patients also had to fail the pragmatism test to be assigned to EVAR 2. As the Outcomes Committee study was a retrospective analysis a pragmatism test could not be applied (although the EVAR 2 and IDE high-risk patients were equivalent in terms of age and AAA size, and the prevalence of cardiac, renal, and pulmonary risks was comparable), it is possible that EVAR 2 patients were sicker, overall, than those analyzed in the Outcomes Committee study. The study continues: “The impact of the pragmatism test was not emphasized in the EVAR 2 report, but this additional criterion is likely another major reason why 30-day mortality in EVAR 2 was 9%. This was apparently an extremely ill group of patients, and it is clear from EVAR 2 that there are patients who are far too ill for any form of AAA therapy.”
The report concludes: “Analysis to four years indicates that EVAR provides excellent protection from aneurysm rupture and AAA-related death, with no significant difference from open surgical controls. High-risk patients found to have an extremely short life expectancy from non-aneurysmal disorders may be appropriate candidates for watchful waiting. For the rest, in the presence of suitable aortic anatomy, EVAR may be the best treatment option.”
In addition, White claims this dataset must be used to represent what happened in the US: “Regardless of what European data may say, in the US we need a point of reference for comparison and decisions that represent the US experience, and this is by far the best database on which to make that assessment. We should not be using a European experience to make decisions for the US. We would like AHRQ to consider these data and potentially in the future use the Outcomes database.”
At this year’s SVS annual meeting there will be a session raising all the arguments surrounding EVAR in high-risk patients. Entitled, “Endovascular Aneurysm Repair (EVAR) in High Risk Patients: A Critical Review of Levels of Evidence,” and sponsored by the Steering Outcomes Committee, this discussion will feature representatives from the AHRQ, the FDA and EVAR investigators from the US (Dr Roy Greenberg) and Europe (Professor Roger Greenhalgh). The session begins at 1.30pm on Saturday 3rd June.