A deeper look at the data from a randomized trial of unruptured brain arteriovenous malformations (AVMs), known as ARUBA, shows that outcomes (death or stroke) among those treated with interventional therapy compared with medical therapy were worse than previously known. Data from the new five year-analysis were presented here on Saturday at the AAN Annual Meeting.
The investigators examined functional impairment as defined by a modified Rankin Scale score (mRS) of 2 or greater at the time of death or stroke. They also compared the frequency of functional impairment and its association with both the score on the Spetzler-Martin Grading Scale and primary outcome events in both the medical therapy and interventional groups. The Spetzler-Martin Grading Scale assesses features of intracranial AVMs to determine operability of AVMs on a scale of 1 to 6; a grade of 6 describes inoperable lesions.
They found that after a median follow-up of 42 months the risk of functional impairment after a primary outcome event was significantly lower (HR 0.26, 95%CI 0.12-0.57) for patients randomized to medical management compared with interventional treatment, which included neurosurgery, embolization, or stereotactic radiotherapy, or a combination of those interventions chosen by the participating center. The Spetzler-Martin Grade and primary outcome events were not associated in the medical arm (p=0.80), but were associated with increasing grades in the interventional arm (p=0.0002).
"Enough details exist now to show that the adverse events in the interventional arm occurred for the most part very early — often the day of initiation — while those in the medical arm occurred later, some of them much later, and not clustered in time," said J.P. Mohr, MD, FAAN, the Daniel Sciarra professor of neurology at Columbia University and the trial's co-principal investigator. "More important, the few outcomes in the medical arm were clinically mild compared with the more serious ones from intervention."
"At five years follow-up, the trial looks like it justifies watchful waiting, hoping that either no spontaneous hemorrhage will occur in this lifetime condition or that if it does the effect will be clinically mild," at which time intervention can be tried to eliminate the AVM, Dr. Mohr said.
Commenting on the study, Dileep Yavagal, MD, FAAN, director of interventional neurology at the University of Miami, said the findings dovetail with his own experience. He agreed that "watchful waiting is the better management strategy" for these AVMs.
The "one clear exception" to watchful waiting, he said, would be cases with "feeding-artery" aneurysms that are more than 4-5 mm in size associated with the AVMs. In those cases, interventional treatment may be indicated to treat the aneurysms even if we do watchful waiting for the AVMs."
Issam Awad, MD, FACS, director of neurovascular surgery at the University of Chicago, said, however, that the problem with the study is "that most patients with unruptured AVMs undergo treatment decisions to purchase a natural risk over a life expectancy horizon of several decades and not merely 42 months."
Another issue, he said, is that all the treatments were combined, without the benchmarking of therapeutic objectives or outcomes.
Dr. Mohr said he would like the neurologic community to focus not so much on problems associated with intervention but on the success of medical management in ARUBA's patients. "We prefer to focus attention on those who did not have the intervention," he said. "Their benign outlook is the least arguable of all the findings."