Fifteen-Year Follow-Up Data From UK EVAR 1 Trial Published

October 20, 2016—Fifteen-year follow-up data from the landmark randomized controlled United Kingdom endovascular aneurysm repair trial 1 (EVAR 1) were published by Rajesh Patel, MD, et al online ahead of print in The Lancet. EVAR 1 was led by Chief Investigator Prof. Roger Greenhalgh, MD, and colleagues, with the Vascular Surgery Research Group at Imperial College London in London, United Kingdom. The 15-year data were first presented at the Charing Cross International Symposium in April 2016.

With a goal of investigating whether EVAR had a long-term survival benefit compared with open repair, the randomized controlled trial enrolled 1,252 patients at 37 centers in the United Kingdom between September 1, 1999 and August 31, 2004. Patients had to be aged 60 years or older, have aneurysms of at least 5.5 cm in diameter, and be deemed suitable and fit for either EVAR or open repair.

Eligible patients were randomly assigned to undergo either EVAR (n = 626) or open repair (n = 626); no masking was used, and patients and treating clinicians were aware of group assignments. The primary analysis compared total and aneurysm-related deaths in the groups until mid-2015 in the intention-to-treat population.

As detailed in The Lancet, over a mean of 12.7 years (standard deviation, 1.5 years; maximum, 15.8 years) of follow-up, the investigators recorded 9.3 deaths per 100 person-years in the EVAR group and 8.9 deaths per 100 person-years in the open repair group. Through 6 months after randomization, patients in the EVAR group had a lower mortality rate. However, beyond 8 years of follow-up, open repair had a significantly lower mortality rate (total mortality, P = .048; aneurysm-related mortality, P = .0064). The increased aneurysm-related mortality in the EVAR group after 8 years was mainly attributable to secondary aneurysm sac rupture (13 deaths [7%] in EVAR vs 2 deaths [1%] in open repair), with increased cancer mortality also observed in the EVAR group. Twenty-five patients had been lost to follow-up by June 30, 2015 (four for mortality outcome).

The overall conclusion reached by the investigators was that EVAR has an early survival benefit but an inferior late survival compared with open repair, which needs to be addressed by lifelong surveillance of EVAR and reintervention if necessary.

Discussing the published data with Endovascular Today, trial investigator Prof. Janet T. Powell, MD, with the Vascular Surgery Research Group, stated, “These data show that during the very long-term follow-up period of 8 to 15 years, both aneurysm-related and all-cause mortality were higher in the EVAR group than in the open repair group. The reasons for this include a continuing higher reintervention and secondary rupture rate after EVAR than after open repair, as well as a suspicion of an increase in late cancer deaths in the EVAR group. However, over the entire 15 years, there was no significant difference in mortality between the groups. The preliminary results from the DREAM trial would appear to support these findings. Therefore, it is a worry that after an elective EVAR, some form of lifelong surveillance is likely to be needed. Similar long-term follow-up data of patients with newer devices would be needed to overturn the lifelong surveillance recommendation."

“These new EVAR 1 results add further fuel to the debate as to whether the youngest and fittest aneurysm patients should be offered open repair,” concluded Prof. Powell.

Also discussing the EVAR trial 1 findings with Endovascular Today, Tara Mastracci, MD, with Royal Free London NHS Foundation Trust, commented, “The most important take-home message from EVAR 1, in my estimation, is the example the investigators provide to the field by their commitment to long-term follow-up, which reflects a tacit understanding that our treatment of aortic disease will be best informed by following results over time. Sadly, even in the context of protocolized follow-up, it revealed that neither open nor endovascular patients were maintaining the necessary long-term relationships with a surveillance modality over time. The results themselves showed no difference in outcome between EVAR and open surgery over the entire follow-up period, with a ‘decay’ of the benefit of EVAR in the later years of follow-up."

Long-term data naturally come with limitations regarding direct application to modern practices, such as those noted by the trialists in The Lancet, including the use of early generation devices that have since seen considerable enhancement. Similarly, operator experience has grown, imaging capabilities have improved, and follow-up protocols continue to change. To this point, Dr. Mastracci noted, "As evidence-based endovascular interventionists, I think it’s important to interpret these results with caution. Even though the trial was designed to only include patients ‘on indication for use,’ our understanding of what makes a healthy and durable landing zone has changed in the 2 decades since the trial was designed, compromising the generalizability of this message to today’s practice. In addition, it is disappointing that a historic view of reintervention as ‘failure’ permeates this report." 

Dr. Mastracci added, "There are many minimally invasive options for treatment of endoleak or disease progression that can prevent late rupture. The lack of anatomic or specific endoleak data and the vague reporting on reintervention make it difficult to glean any messages to guide practice.”

In their conclusion, the EVAR 1 investigators also noted modern patient preference for EVAR and a trend in declining operator experience in open repair.

Contextualizing their findings in the current landscape, the trialists believe these data "can act as a benchmark against which new endovascular technologies for aneurysm repair can be compared with at each time point."