Title: Late aneurysm-related mortality up to 15 years, secondary endovascular repair, late sac rupture risk, costs & cost effectiveness implications in the United Kingdom EndoVascular Aneurysm Repair randomised controlled trials and management of type II endoleaks
Funder: Department of Health and Social Care

Abstract: 1. Design: Extended follow up of randomised controlled trials EVAR 1 and EVAR 2 from 2010 until 2014. The follow up will be obtained retrospectively for 2010 & 2011 and prospectively for 2012, 2013, 2014. The proposal has ethical approval by the North West Multi-centre Research Ethics Committee (MREC, Ref Number 98/8/26 & 27). 2. Setting: Hospital records and diagnostic radiology departments for CT scans performed for EVAR trials patients alive at the 34 centres in England, Scotland and Northern Ireland. 3. Target population:Initial EVAR trials patients were recruited of both sexes, aged 60 years and over and ones with an aortic aneurysm of greater than 5.5cm and anatomically suitable for EVAR. In EVAR trial 1 they were fit for open repair and in EVAR trial 2 they were not. 4. Health technologies being assessed: Endovascular repair of abdominal aortic aneurysm compared with open repair (OR) in EVAR trial 1 and compared with medical treatment alone in EVAR trial 2. 5. Measurement of costs and outcomes:The primary outcome is aneurysm-related mortality of EVAR and OR in EVAR trial 1. All cause mortality of EVAR and OR in EVAR trial 1 with incidence of complications, reinterventions, patterns of sac growth and sac rupture of EVAR in EVAR trials 1 & 2 as well as core laboratory CT scan analysis of endoleaks are supportive end points. Cost-effectiveness:The EVAR trials have enabled a number of detailed cost-effectiveness analyses of these interventions, with the latest based on 10 years follow-up. The proposed data collection will facilitate two types of updated analyses. First, the “within-trial” analyses will estimate mean total costs and quality-adjusted life years (QALYs) of the randomised interventions based on the individual patient data up to 15-years in EVAR 1 and EVAR 2. The primary analysis will include the costs to the NHS of the interventions and aneurysm-related complications and reinterventions. Unit cost will be obtained from national databases and published literature. We will investigate whether the most suitable source of current information on the cost of the devices is likely to be an updated hospital survey, or whether NHS administrative data might be available. Secondary analyses will include the short and long term costs of systemic complications such as myocardial infarction, stroke, amputation and renal failure. Confidence intervals will be estimated by Monte-Carlo methods. Censoring and other types of missing data will be handled using appropriate method for costs and QALYs. Second, modelling will be used to estimate lifetime costs and QALYs associated with EVAR versus open repair. Survival analysis will be used to estimate the rates of aneurysm- related mortality in the trial (as assessed by an independent end-points committee) and reintervention rates associated with each intervention. These data, together with expert opinion will be used to extrapolate absolute rates of events beyond 15 years. Assumptions will be made about how the relative treatment effect might continue beyond the trial. This analysis will incorporate evidence from other relevant trials and observational studies, and will permit a wide range of sensitivity analyses to be carried out. 6. Sample size: All EVAR trials patients alive in September 2009 are included in this extended follow up. The surviving target population for each year is expected to be 2010 (982), 2011 (899), 2012 (828), 2013 (763), 2014 (704). Thus it is expected to obtain 4176 additional annual patient follow-ups. 7. Project timetable: Retrospective follow up for years 2010 and 2011 and prospective for 2012, 2013 an 2014. Nine months analysis and reporting from January 2015.

Lay abstract: The question addressed is whether at 15 years after abdominal aortic aneurysm repair, death attributed to aneurysm of the aorta, a swelling of the main artery of the body, is higher for the newer endovascular aneurysm repair (EVAR) technology than the original open repair (OR). This would be despite every effort being made at the vascular centres to correct leaks after EVAR to reduce aortic sac rupture, after which two thirds of patients have died. This would inform clinicians and future patients of risks and enable a reappraisal of comparative costs and cost effectiveness of both treatments. It is important to the NHS at this time especially because of the UK National Abdominal Aortic Aneurysm Screening Programme, which will require more men over 65 years to undergo aortic aneurysm correction by one of the above methods. In the first 10 years of follow up in two UK trials, 27 sac ruptures were reported in patients receiving EVAR and another 29 are anticipated with 5 more years of follow up. The likely cause of the late sac ruptures is now known and there is a need to ensure that urgent correction occurs in these patients. Even then, it is possible that open repair could be more durable at 15 years. Costs and cost effectiveness outcomes could be hugely affected if these events continue occurring up to 15 years after aneurysm repair. These UK trials were the world's first randomised controlled trials with a 10 year follow up. EVAR is only possible if the shape of the aorta is suitable (greater than 50%). Trials in the Netherlands, France and the US were based on the UK trial design and these trials suggest that the early EVAR mortality benefit does not persist. Uniquely, the UK trials used aneurysm-related mortality as an end point as well as all cause mortality, knowledge of sac growth and the underlying factors associated with sac ruptures. Over a further five years of follow up and with control of EVAR late leaks, aneurysm-related mortality knowledge should inform comparative long term results with patient choice and cost comparison implications.

Research activity codes: 6.4 SURGERY
Health categories: CARDIOVASCULAR