LOS ANGELES—Patients who undergo invasive interventions to repair an unruptured arteriovenous malformation (AVM) in their brain have a greater than twofold increased rate of death or stroke during an average four years of follow-up, compared to patients who receive medical treatment alone with no active intervention, said Christian Stapf, MD, Professor of Neurosciences at the University of Montreal.
When analyzed on an intention-to-treat basis, for every five patients with AVM treated with endovascular surgery, conventional surgery, or radiotherapy, one additional patient died or had a stroke, compared with the death or stroke rate among control patients who received only medical management. When analyzed based on the treatments that patients actually received, the researchers identified one excess death or stroke for every three patients with AVM who underwent an invasive procedure, compared with control patients, Dr. Stapf reported at the International Stroke Conference 2016.
The results from A Randomized Trial of Unruptured Brain AVMs (ARUBA) “show us that we clearly have not been as good as we thought in helping patients against their stroke risk,” said Dr. Stapf. “Given that the risk of death or stroke was reduced three- to fivefold with no [invasive] treatment and leaving the AVM alone makes us think that we can’t recommend preventive intervention with currently used techniques. Living with the AVM seems like the far better option.”
Enrollment Was Stopped Prematurely
The ARUBA study was conducted at 39 centers in nine countries, including 13 US centers. Researchers randomized 226 patients with unruptured AVMs before the study’s data safety and monitoring board stopped study enrollment prematurely in April 2013. The study group included 110 patients randomized to receive medical interventions only and 116 randomized to medical intervention plus “best possible” AVM eradication. The exact type of eradication for each patient was left up to local clinicians, who tailored the intervention to address the size, location, and anatomy of each AVM. Medical management included steps such as treatment with antiepileptic drugs to reduce seizures, various treatments for headache, and physiotherapy for patients with neurologic deficits.
The study’s primary end point was the combined rate of death or stroke, which occurred in 41 of the 116 patients (35%) randomized to receive an invasive intervention and in 15 of the 110 (14%) randomized to medical treatment only. The average follow-up period was 50 months, and many patients were followed for five years.
When analyzed by the treatment patients actually received, 106 underwent an invasive intervention, and 43 of these patients (41%) died or had a stroke. In addition, 120 patients received medical treatment only, and 13 (11%) of these patients died or had a stroke.
A secondary end point was the rate of death or disability after a five-year follow-up. Disability was defined as a modified Rankin Scale score of 2 or more. This outcome occurred in 38% of the 45 patients who underwent AVM eradication and had this follow-up available, and in 18% of 51 patients who had medical treatment only and received this follow-up.
Invasive Interventions May Become Less Common
Interim results from the study were published two years ago. The average follow-up period at that time was 33 months, but the trial was designed to have a five-year follow-up. This goal largely was accomplished in the new data reported by Dr. Stapf.
Many clinicians had already abandoned invasive interventions to treat brain AVMs following the publication of the interim results. Dr. Stapf predicted that this trend would strengthen further, now that the final results are available and confirm the earlier indication of hazard. Until the ARUBA results became available, clinicians presumed that invasive interventions to resolve or minimize malformations were beneficial. ARUBA is the first systematic comparison of procedures versus no active intervention for brain AVMs, said Dr. Stapf. “Neurologists will now be less likely to refer patients for intervention, and interventionists will be less enthusiastic to perform procedures,” said Dr. Stapf. In addition, anyone now performing an intervention in routine practice would need to consider the possible legal implications if the patient were to have a bad outcome. Dr. Stapf also noted that some professional societies are considering recommendations against routine interventions. He conceded that some invasive interventions might still occur for selected cases on an investigational basis, but the ARUBA results “set the bar very high against performing any new interventions,” he concluded.
Approximately 3,000 patients annually are newly diagnosed with an unruptured brain AVM in the United States and Canada, he estimated.
—Mitchel L. Zoler