The OVER trial investigators, led by the late Frank Lederle, recently released the long-term results of endovascular aneurysm repair (EVAR) versus open repair. Janet Powell writes for Vascular News about the 14-year outcomes, which were published in the New England Journal of Medicine, how they compare to other similar randomised controlled trials’ results, and what the data contribute to the ongoing conversation about the durability of EVAR.
The publication of the very long-term results of the OVER trial realises the last main research aim of Frank Lederle: he was still working on this a couple of months before his untimely death from pancreatic cancer. So, congratulations to Frank and the team that persisted in seeing this through to publication. When Frank presented the preliminary findings at the European Society for Vascular Surgery (ESVS) Lyon in September 2017, there was a possibility that the late survival would be better in the EVAR group, but the data were not yet complete. Now, like the EVAR-1 and DREAM trials, the OVER trial has shown that over the 14 years of follow-up there was no difference in survival—the main outcome—between the open repair and endovascular groups. These three trials also agree that the burden of reinterventions over 14 years is much higher in the EVAR group, and this remains a worry in cost-conscious health economies. The fourth trial, the ACE trial from France, has no long-term patient follow-up.
Although concordant in their principal findings, there are some differences in the secondary outcomes reported from the OVER trial—particularly cause of death. The explanation for this likely emanates from differences in patient selection and the methodology used for late follow-up. It is not correct to suggest that the OVER trial used more technologically advanced endografts than the other trials: it was the only trial to use a significant number of AneuRx (Medtronic) endografts. Equally, the OVER trialists’ suggestion, that the US surgeons perhaps were more highly skilled than their European counterparts, is not evidence-based.
Though no trial recruited more than 10% women, the OVER trial recruited almost none. Their patients were much younger, had significantly smaller aneurysms and a much lower burden of coronary artery disease, but double the proportion of patients with diabetes or current smoking compared with the EVAR-1 trial. These differences are likely to impact upon secondary outcomes. For instance, the high prevalence of diabetes (which is associated with slower aneurysm progression) in the OVER trial patients might have contributed the lower reported rate of secondary rupture after EVAR compared to the EVAR-1 trial. The low rate of secondary rupture and late aneurysm-related death reported in the OVER trial also might have resulted from methodological differences between the late follow-up in the OVER and EVAR-1 trials. In the EVAR-1 trial all deaths and clinical events were adjudicated by an independent end-points committee and clinical events from routine data validated by hospital records. In the OVER trial all deaths and clinical events since 2011 (more than half the deaths) were obtained from routine administrative data only and not adjudicated by an independent committee. Instead, the authors of the OVER trial paper attributed the cause of late deaths. Moreover, in 93 (≈25%) of the late deaths, there were insufficient data for the authors to assign a cause of death. Under such circumstances, together with important differences in baseline characteristics, it is probably unwise to compare the secondary outcomes of aneurysm-related mortality or other causes of late death between the OVER and EVAR-1 or DREAM trials.
Interestingly, the OVER trial reported that in patients aged 70 years and older, the long-term overall survival was lower in the EVAR group than in the open repair group (and the converse for those <70 years). Similar observations have been made from MEDICARE data. This raises an important question about endograft fixation in the aging aorta: “Does fixation become more tenuous with age, due to ongoing degenerative aortic disease?”
In summary, three randomised trials have shown that the early survival advantage of EVAR versus open repair is not maintained and that after 14–15 years, and there is no difference in overall survival between the two treatment groups despite the increased number of reinterventions in the endovascular groups. Since the inclusion/eligibility criteria for all three trials specified that the morphology of the aneurysm should be within instruction for use (IFU) of the proposed device, these results may not apply to the increasing number of patients who have had endografts outside IFU, with or without adjunct procedures: their reintervention and mortality rates might be much higher than those in the randomised trials. The quest now is how to ensure the durability of the new generation of endografts and provide judicious surveillance to ensure that endovascular treatment is cost-effective, with ever-improving outcomes for future patients.
Janet Powell is a visiting professor of Vascular Biology and Medicine at Imperial College, London, UK.