The OVER trial, a decade later, holds some surprises
The early survival advantage from endovascular abdominal aortic aneurysm (AAA) repair fades over time in comparison with standard open repair, long-term randomized trial data confirmed, though patient age may make a difference.
All-cause mortality came out similar between endovascular and open repair after up to 14 years of follow-up (68.0% vs 70.0%, HR 0.96, 95% CI 0.82-1.13), according to Tassos Kyriakides, PhD, and collaborators reporting in the May 30 issue of the New England Journal of Medicine.
These data from the OVER Veterans Affairs Cooperative Study Group appear to contradict DREAM and EVAR-1, two European trials that found greater long-term mortality with endovascular repair.
As was the case in the previous report of up to 9 years of follow-up (mean 5.2) from the trial, patients younger than age 70 trended toward better long-term survival with endovascular instead of open repair (HR 0.81, 95% CI 0.62-1.05), whereas older individuals seemed to do better with open surgery (HR 1.20, 95% CI 0.98-1.47).
Even though the test for interaction turned out to be significant (P=0.02), neither of these findings reached statistical significance. No correction was made for multiple comparisons either, the authors cautioned.
Nevertheless, it's a surprising signal, according to Kyriakides' group. "Much of the early enthusiasm for endovascular repair focused on an expected advantage in old or frail patients who were not good candidates for open repair."
"The clinical implications of this age effect must be reconciled with our finding that all ruptures of infrarenal aneurysms occurred in the endovascular-repair group, which makes this procedure seemingly less desirable for use in younger patients. However, the percentage of ruptures in our trial was low (0.9%)," they noted.
Further confirmation of the age effect is required as it runs "contrary to what we would have intuitively expected," according to Ageliki Vouyouka, MD, of Icahn School of Medicine at Mount Sinai in New York City.
Over the median 9.4 years of follow-up in the trial, different trends emerged as time went on:
- First 4 years: Survival odds higher with endovascular repair
- Years 4-8: Survival better with open repair
- After 8 years: Survival again favored the endovascular procedure
Now, according to the investigators, the key questions are: What caused the later deathsin the endovascular-repair group? And could endovascular repair end up being the inferior strategy?
"The first question remains unanswered, but the most widely accepted explanation is that the perioperative deaths after open repair most likely occurred in the frailest patients, so the curves converged as later deaths occurred in the frailest patients in the endovascular-repair groups," they said.
As for the second question, the study showed numerically fewer deaths beyond 8 years in the endovascular-repair group than in the open-repair group (HR 0.94, 95% CI, 0.74-1.18), very few late aneurysm-related deaths in either group, and little evidence for a late increase in secondary therapeutic procedures after endovascular repair.
"Even though the result of the primary analysis (the hazard ratio) suggests that there is no significant difference in the outcome between the two groups, an assessment of the hazard ratio at various time periods suggests that this estimated overall hazard ratio might not be a good summary statistic for long-term follow-up," Kyriakides and colleagues argued.
The 881 patients enrolled in OVER came from 42 Veterans Affairs medical centers. Baseline characteristics were similar between groups, except there were more individuals taking aspirin assigned to open repair.
Other outcomes noted over long-term follow-up included:
- No significant difference in aneurysm-related deaths: 2.7% with endovascular vs 3.7% with open repair
- Significantly more aneurysm ruptures with endovascular repair: 1.6% vs 0.2%
- A nonsignificant trend for more death from chronic obstructive lung disease with open repair: 5.4% vs 8.2% (-2.8 percentage points, 95% CI -6.2 to 0.5)
"Chronic obstructive lung disease caused just over 50% more deaths in the open-repair group than in the endovascular-repair group. This difference was significant, and it is supported by strong trends in the two European trials," Kyriakides and colleagues commented.
The study was supported by the Department of Veterans Affairs.
Kyriakides disclosed no relevant conflicts of interest.
Study co-authors listed ties to Medtronic, Gore, Cook, Covidien, Endologix, and Abbott.
New England Journal of Medicine
Source Reference: Lederle FA, et al "Open versus endovascular repair of abdominal aortic aneurysm" New Engl J Med 2019; DOI: 10.1056/NEJMoa1715955.
Read the original article on Medpage Today: For AAA Repair, Age May Not Work as Expected