Information for clinicians and trialists
Contact the trial team
Trial email: warriors@imperial.ac.uk
Janet Powell: j.powell@imperial.ac.uk
Colin Bicknell: colin.bicknell@imperial.ac.uk
Anna-Louise Pouncey: a.pouncey@imperial.ac.uk
Funders
British Heart Foundation, with additional support from Medtronic, Terumo Aortic and internationally from Finnish Heart Foundation, Swedish Heart & Lung Foundation, Novo Nordisk, Denmarks Frie Forskningfond, and Vascular Foundation Australia.
Research aim
To assess whether women with small abdominal aortic aneurysm (AAA) currently are treated too late in their clinical course.
Primary aim: For women with small abdominal aortic aneurysm (AAA, 4.0-5.4 cm diameter), to assess whether early endovascular aneurysm repair (EVAR) compared to routine surveillance decreases the composite outcome of AAA rupture and aneurysm-related mortality over five years.
Secondary aim: For women with small abdominal aortic aneurysm (AAA, 4.0-5.4 cm diameter), to assess whether early endovascular aneurysm repair (EVAR) compared to routine surveillance increases quality-adjusted-life-years (QALYs) over five years.
Other aims: to compare operative mortality, major cardiovascular events (MACE), all-cause mortality, costs and cost-effectiveness between the two randomised groups. Also, in the surveillance group to assess the rate of losing eligibility for EVAR as the AAA expands.
Trial information
Women have smaller arteries and lower AAA population prevalence, but this is disputed and dependent on diagnostic threshold. AAA is ~5 times more common in men if a 3 cm diameter threshold is applied but only ~1.3 times greater when an increase of >1.5 times the normal infrarenal aortic diameter is used. Women were under-represented in the four major randomised trials of small asymptomatic AAA repair, comprising on average only 4.3% of participants. These trials have defined the risk-benefit and intervention threshold for AAA in men, but do not represent women. This is highly pertinent, as women have 4 times greater rupture risk of small AAA. Individual patient meta-analysis (15475 people) demonstrated that in women the rupture risk at 4.2cm diameter was the same as at 5.5cm for men. Increased AAA size is also associated with increased operative complexity and peri-operative mortality. Every 1 cm increase in diameter is associated with an 18% increase in adjusted odd of 30-day mortality for open repair. For endovascular aneurysm repair (EVAR or keyhole surgery), increased size is also significantly associated with a reduction in both 30-day and 5-year survival. Systematic review with meta-analysis demonstrates that women have higher operative mortality and complications rates than men - 30-day mortality following elective open repair is 6% and for EVAR 2.3% (odds ratio versus men 1.49 and 1.86 respectively even after adjustment for co-morbidities). These disparities are consistent worldwide and have not ameliorated with time. With a 30-day mortality of 6% open repair cannot be considered a safe elective procedure for women. EVAR is the preferred treatment modality among most AAA patients. Eligibility for EVAR by anatomical criteria declines at significantly lower AAA diameter for women compared to men. At the 5.5 cm diameter threshold, women are less likely to be selected for endovascular repair than men (34% vs 54%) and more likely to be selected for conservative management (34% vs 19%). Overall, women are 25% less likely to receive elective AAA repair, but increasingly likely to present with AAA rupture, which carries >10-fold increased mortality. Therefore, it is possible that the opportunity for effective AAA treatment in women is being missed. While various retrospective analyses have called for sex-specific criteria for AAA repair, without dedicated prospective research, uncertainty regarding the risk-benefit threshold and sex-specific disparity in AAA repair remain.