Professor Roger Greenhalgh, London, UK, launched a robust defence of the UK EndoVascular Aneurysm Repair (EVAR) trials at the recent annual meeting of the Society for Vascular Surgery (SVS), in Philadelphia, PA. In the session entitled, “Endovascular Aneurysm Repair (EVAR) in High Risk Patients: A Critical Review of Levels of Evidence”, organised by Gregorio Sicard, chairman of the Outcomes Steering Committee of the SVS, presentations were given by the Agency for Healthcare, Research and Quality (AHRQ), the Food and Drug Administration, as well as the Cleveland Clinic (Dr Roy Greenberg) and the UK EVAR Trial Manager (Louise Brown).
The SVS has recently published data from its Lifeline Registry that seemed to show that mortality compares “favourably” with EVAR 2 in the short-term (30-day mortality: 2.9% US IDE, 9% EVAR2) and to four years (44% US IDE, 64% EVAR 2). To try to match the EVAR 2 definition of unfit, the Lifeline Registry data defined high-risk as patients aged >60 years, with a pre-procedure aneurysm diameter of >5.5 cm and at least one co-morbidity (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 patients met this high-risk definition. The remaining 1,651 EVAR and 281 open patients were considered normal risk.
Outcomes
Results from the dataset revealed a 30-day operative mortality rate of 2.9% for EVAR in this high-risk patient cohort compared with 5.1% for open repair. One AAA-related death occurred in the interval from 30 days to one-year in the EVAR group and none in the open repair group. 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 that no significant difference was identified in all-cause mortality between EVAR and open repair throughout 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 US IDE EVAR patients was also compared with the normal-risk US IDE EVAR patients. The high-risk EVAR mortality rate was twice that of the non-high-risk patients (44% vs 21).Unfit or high risk
However, at the SVS session Greenhalgh showed that the definitions used by the Lifeline Registry and the EVAR 2 trial were not the same by comparing all cause mortality survival curves to EVAR 1, EVAR 2 and the Lifeline series. EVAR 2 patients died much faster with or without EVAR. A validated fitness scoring system was described by Louise Brown and applied to EVAR 1 and 2 series. This showed that they were quite different with EVAR 2 patients, very sick. The additional analysis which grouped patients in the EVAR trials according to fitness showed that at all levels of fitness EVAR was better than open repair but that the benefit was greater for EVAR the fitter the patient. Thus, in the very, very unfit EVAR 2 situation the patient is not only unfit for open repair but EVAR fails to help.
Greenhalgh explained that the EVAR 2 triallists took a pragmatic approach to fitness for open repair but noted details of respiratory, renal and cardiac risk. “We know that some patients improved, crossed over and did quite well on the delay while others died before intervention. Understandably then, during this trial, the accent was to get EVAR done as this would reduce rupture risk and death. It did not and the triallists were staggered! After a pause, they commented that the accent should move to improving patient fitness.”
Greenhalgh commented that Greenberg for the Cleveland Clinic group reports an uncontrolled single centre experience, saying that EVAR can be done with 1.9% mortality in patients unfit for open repair. In addition, he added that Bush, for the Houston group report on the Veterans Affairs (VA) national surgical Quality Improvement Programme reported that “30 day mortality in EVAR 2 was 2.9 times higher (3.1% vs 9%)”, but the VA series includes ‘high risk patients’ who were deemed fit enough for open repair.
Greenhalgh noted that Sicard et al conducted the study “to determine the outcome in the US after EVAR in patients at high risk for open surgery by using independently audited, high compliance, chart-verified data sets, and compare those results with open surgery”. High risk was defined “to match a recent European trial” (EVAR 2). “The controls taken were said to meet ‘high risk criteria’. Nevertheless, 342 surgical controls were deemed fit for open repair, although the authors still say they were matched.” Greenhalgh commented, “Thirty-day mortality was 2.9% for EVAR and 5.1% in open repair. There was no statistical difference between the series either in terms of all cause or AAA-related mortality.”
Greenhalgh added, “Are data from the SVS registry useful? Yes. Do they alter EVAR 2 findings? No.” He admitted that the EVAR 2 findings surprised the clinicians involved as well as the rest of the world. He continued, “Interpretations of a properly powered randomised control trial (RCT) can be a problem in itself, but as Bertrand Russell said 50 years ago, “When confused, go back to the original data.”
“Sadly a registry is only as strong as data sent to it. What is not sent is not analysed. An RCT traps all data. An RCT develops a plan before looking at results to avoid bias. A registry already flawed in terms of completeness of data collected can be used ‘with the end in mind’. Thus it does not improve credibility that it has been an open secret that their data would be trawled with an end in mind.”
In the meantime, there has been regulatory interest. The National Institute for Clinical Excellence in the UK will consider if EVAR is “safe and effective” in patients unfit for open repair.
