LONDON, United Kingdom — More details of the results of the ARUBA study, evaluating the best management of unruptured arteriovenous malformations (AVMs) in the brain, were reported here at the XXII European Stroke Conference (ESC).
ARUBA (A Randomized trial of Unruptured Brain Arteriovenous malformations) compared interventional vs conservative treatment and was stopped earlier this year because of a higher than expected event rate in the interventional group.
The trial had enrolled 223 of a planned 400 patients; 109 were randomly assigned to conservative treatment and 114 to an interventional approach. Interventions used could be endovascular embolization, neurosurgical excision, stereotactic radiosurgery, or a combination of these techniques. Patients were well matched at baseline; most had Spetzler-Martin grades of 1, 2, or 3. There were a few grade 4s but no grade 5s (hazardous to treat).
At the time of stopping, the average follow-up was 3 years. There were some crossovers between the groups, with 17 patients allocated to the interventional group not actually receiving an intervention, and 6 patients assigned to conservative treatment who received an intervention.
The trial was stopped by the data safety monitoring board in April 2013 because the predetermined threshold for safety/efficacy had been met.
Presenting the results, Jay P. Mohr, MD, Columbia University, New York, New York, reported that the primary outcome (death or stroke) had occurred in 11 patients in the conservative group (10%) vs 33 patients (29%) in the interventional group. The intention-to- treat analysis showed a significant reduction of the primary outcome in the conservative group, with a hazard ratio of 0.35 (95% confidence interval [CI], 0.19 - 0.65). The interventional group also had higher modified Rankin scale scores.
The per-protocol analysis showed an even larger difference between the 2 groups, with a hazard ratio of 0.20 (95% CI, 0.10 - 0.41).
Dr. Mohr concluded that "at the time the trial was stopped medical management was superior for the prevention of death or stroke." But he added: "We are seeking funding for long-term follow-up that we feel is essential to determine if the disparity between the two groups persists over time or if there is a degree of convergence."
What About the Long Term?
In an interview with Medscape Medical News, ARUBA investigator Rustam Al-Shahi Salman, FRCP, University of Edinburgh, United Kingdom, said, "The early hazard of interventional treatment has been clearly demonstrated in this study. And we can say with some certainty that conservative treatment is better in the short term. But the dilemma we still have is that we don't know if this difference will remain long term. This is likely to be the only randomized trial conducted in this area, and we will need to follow these patients up long term."
Dr. Al-Shahi Salman explained that about 1 in 2000 people are estimated to have an unruptured AVM. In general if left alone an unruptured AVM carries an annual risk of bleeding of about 1%, and about 10% of the bleeding episodes may be fatal.
"So for 1000 patients with an AVM, 10 will bleed in one year, and one may die. So the annual risk is quite low but the risk is thought to stack up over a lifetime. It is recognized that interventional treatment for AVMs does carry risks and these may vary by procedure types and characteristics of the individual AVM. A few observational studies have suggested this increased early risk, and now we have shown it clearly in a randomized trial. The big question now, however, is how long will it take, if ever, for the two curves to cross."
Dr. Al-Shahi Salman said that although these results would obviously make him think very carefully before recommending interventional treatment for an unruptured AVM, he would not rule out the possibility of the interventional route altogether. "These results provide me with some robust data with which to talk to patients about the decision-making process."
He added that future analysis would explore whether any particular group of patients could be identified in whom the risk of intervention may be less and would look at the cause of the deaths in the study. "Not all of the deaths in the study were due to the AVM, and we need to look at this more carefully."
XXII European Stroke Conference (ESC). Large Clinical Trials C: 1. Presented May 31, 2013.
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Cite this: Sue Hughes. ARUBA: Conservative Management of AVM Best in Short Term - Medscape - Jun 14, 2013.
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