Results from the 12-month data of the randomised controlled IMPROVE trial, presented for the first time at CX 2015 (28 April–1May, London, UK), show that an endovascular strategy is cost-effective when compared to open repair in the treatment of ruptured abdominal aortic aneurysms. The one-year data also revealed that the endovascular strategy conferred no survival benefit over open repair, except a trend towards benefitting women. It also showed that the endovascular strategy enabled more patients to be discharged from hospital to home, and significantly faster than with open repair. Patients also have an excellent quality of life with endovascular strategy, if they survive the rupture, delegates heard.
Twelve-month outcomes from the individual patient data meta-analysis of three randomised controlled trials of ruptured aneurysms [ie the Dutch AJAX trial, the French ECAR trial and the UK IMPROVE trial] also showed a trend towards survival benefit for endovascular aneurysm repair (EVAR), but this was not statistically significant. A CX audience poll in the session revealed that nearly 80% agreed that the 12-month results of the IMPROVE trial encouraged them to perform EVAR more often.
Janet Powell, Imperial College, London, UK, presented the latest data from the IMPROVE (Immediate management of the patient with rupture: Open vs. endovascular repair) trial that reported one-year outcomes following either a strategy of endovascular repair first or open repair of ruptured abdominal aortic aneurysm. The results demonstrate no survival benefit for the endovascular strategy for ruptured aneurysm at one year. However, an endovascular-first strategy for the management of ruptured aneurysms does offer patients faster discharge with better quality of life and it is also cost-effective. Both these factors are necessary for patient and clinical decision-making, delegates heard. These data were published in April in the European Heart Journal (EHJ).
IMPROVE, a pragmatic, multicentre (29 UK and one Canada) trial randomised 613 patients with a clinical diagnosis of ruptured aneurysm, 316 patients to an endovascular-first strategy (if aortic morphology was suitable and open repair if not) and 297 to open repair. Powell also drew attention to the fact that at baseline, the characteristics of the two groups were similar with almost three-quarters in each group being men. “The aneurysms in this trial were also very large with average diameters in each group being over 8cm,” she said. The principal one-year outcome was mortality and secondary outcomes were reinterventions, hospital discharge, health-related quality-of-life, costs, quality-adjusted-life-years and cost-effectiveness.
At CX 2015, Powell noted that the trial was designed to answer the question of what to do with a patient who presents to the emergency room with a diagnosis of ruptured abdominal aortic aneurysm. “What we had anticipated was that using an endovascular strategy, wherever it was morphologically feasible, we could reduce 30-day operative mortality from 47% in the open repair group to 33% where endovascular repair was used extensively,” she said.
Powell added: “At one year, all-cause mortality was 41.1% for the endovascular strategy group and 45.1% for the open repair group (p=0.325) with similar reintervention rates in each. A subgroup analysis showed a stronger benefit for the endovascular strategy in women versus men. The endovascular strategy group and open repair groups had average total hospital stays of 17 and 26 days, respectively.
The 30-day mortality results, the primary outcome, previously published in British Medical Journal (BMJ) in 2014, also found no difference in 30-day mortality between the endovascular strategy group and the open repair group and subgroup analysis showed a strong benefit for the endovascular strategy in women compared with men.
Pooled individual patient data outcomes
Ron Balm presented the 12-month outcomes meta-analysis from the individual patient data from the three randomised controlled trials of ruptured aneurysms; the Dutch AJAX trial (Annals of Surgery 2013), the French ECAR trial (EJVES 2015) and the UK IMPROVE trial.
“These were all trials that were performed on patients with a clinical suspicion of ruptured aneurysm. In the AJAX trial the 30-day mortality in both groups was approximately 25%, in ECAR it was 22% and in IMPROVE, which had a slightly different study design, it was 35% in each group (BMJ 2014), but all failed to demonstrate the benefit of EVAR in the emergent setting. “The results were hampered by the fact that open repair performed so much better than we expected,” Balm noted.
The pooled inpatient data was subjected to two different analyses; the first was an analysis as randomised including all patients and the second contained only those patients with proven rupture and a restricted cohort from the IMPROVE trial who were anatomically suitable for EVAR.
“The 30-day survival data showed no significant benefit for endovascular repair. A subgroup analysis of age, sex and Hardman disability index showed that age and Hardman index had no influence on the main results, but female sex was identified as benefitting from endovascular repair. The time to discharge alive from primary admission was also significantly better for patients undergoing EVAR when compared to those undergoing open repair. We also looked at the influence of neck diameter, neck length and neck angulation. Longer neck lengths resulted in better survival for all patients,” Balm said.
In the pooled results of all patients, the three-month mortality rate included only those patients who were fit for endovascular repair, which reduces the patients in the IMPROVE trial. There seems a benefit for endovascular repair but this is statistically not significant, he said.
Summarising the survival results of all pooled patients to one year, Balm said, there is an advantage for EVAR, but this is statistically not significant.
These findings led Balm to conclude that the early data from the pooled inpatient data meta-analysis did not suggest that there was any survival benefit for EVAR. “At one year, the small survival advantage of EVAR is not significant. Yet, although endovascular repair does not offer a significant survival advantage, endovascular repair should be used more widely. Open repair must remain available for those unsuitable for conventional EVAR,” Balm maintained.
Are patients with ruptured aneurysms being turned down too often?
A small majority of voters, 57%, did not agree with the motion “Too many patients with ruptured aneuryms are denied intervention” in an interesting debate on the topic.
Matt Thompson, London, UK, speaking for the motion, based his arguments on the data from Karthikesalingam et al (The Lancet, 2014), which used UK Hospital Episode Statistics (HES) data and US Nationwide Inpatient Sample (NIS) data to show that in-hospital survival from ruptured abdominal aortic aneurysm, intervention rates, and uptake of endovascular repair are lower in England than in the USA.
Thompson stated that 68% of patients in the UK receive no treatment for rupture. “There is a huge variation in the proportion of patients being offered therapy for ruptured abdominal aortic aneurysm at the regional and international level. Non-interventional treatment is universally fatal,” he said.
Thompson argued that apart from identifying the optimal management strategy for patients with ruptured aneurysms, more emphasis should be placed on treatment rates. “We must do better than refuse treatment to around 60% patients,” he said.
Peter Lamont, Bristol, UK, who persuaded the delegates that ruptured aneurysm patients were not being denied interventional treatment too often, contested the data presented by Thompson because with the HES data it made the assumption that the diagnostic code for ruptured abdominal aortic aneurysm without an operative code for the condition was a turndown. He also pointed out that a 2005 coding audit had found up to 23% HES codes to be incorrect. Further, NIS data misses 80% of patients, noted Lamont.
“Numerous direct audits in 2010 and after in the UK show consistent turndown rates of around 20% by vascular surgeons,” he said.
Lamont pointed to a Vascular Society members audit in 2011 that revealed a turndown rate of 24% and also showed that the average age of patients was 83. “Of these, 24% declined intervention, 14% had dementia and 21% had terminal malignancy/severe chronic disease,” he added.
Lamont concluded by saying that the service reconfiguration in the UK guarantees that vascular surgeons are now on call 24/7 for ruptured abdominal aortic aneurysm. “When comparing like for like, the turndown rates in the UK are similar to those in the USA,” Lamont said.
In the ensuing discussion, Powell made the point that twice as many women than men are turned down for treatment when they present with ruptured aneurysm and asked for a response on why this might be the case. “We did not formally address that in the IMPROVE trial, but there are several observational cohorts to suggest that adopting a more minimally invasive approach would lead to a reduction in turndown rates in these patients,” added Thompson.
Thompson explained the criteria for palliation; patients in whom intervention is completely futile, such as those with advanced malignancy or dementia, who have no quality of life are suitable candidates for palliation. “There are patients in whom it is cruel to intervene as they do not want their life prolonged,” agreed Lamont.
Frank Veith, New York, USA, made the point that the way to decrease the turn down rate for ruptured aneurysms was to embrace endovascular repair.