Conservative AVM Approach Linked to Better Long-Term Outcome

Nancy A. Melville

April 24, 2014

A conservative management approach to unruptured brain arteriovenous malformations (bAVMs) is associated with better long-term outcomes than interventional treatment in patients followed for up to 12 years, a new analysis shows.

"The similarity of the results of this observational study and (the previous randomized) ARUBA trial and the persistent difference between the outcome of conservative management and intervention during 12-year follow-up in our study support the superiority of conservative management to intervention for unruptured bAVMs, which may deter some patients and physicians from intervention," the authors conclude.

Unruptured bAVMs are associated with about a 1% annual risk for intracranial hemorrhage; however, studies show the bleeding can be fatal in about 12% of cases, and the decision on the proper approach for such cases can be clinically challenging.

Interventional therapy, neurosurgery, or radiation therapy carry their own potential risks, as underscored by results of the only randomized to compare long-term outcomes of the 2 approaches, the ARUBA trial.

As reported by Medscape Medical News , that trial was halted by the National Institute of Neurological Disorders and Stroke (NINDS) last year when an interim analysis of 224 patients at 33 months showed the event rate in patients receiving intervention was more than 3 times higher than in the conservative management group.

With guidelines on the controversial issue continuing to endorse both approaches, however, researchers led by Rustam Al-Shahi Salman, PhD, from the University of Edinburgh, United Kingdom, who was also an investigator on the ARUBA trial, sought to further evaluate outcomes in a large population in Scotland.

The findings of the Scottish Audit of Intracranial Vascular Malformations Collaborators are published in the April 23/30 issue of JAMA.

Conservative Management

The study included 204 patients, aged 16 years and older, who experienced unruptured bAVM between 1999 and 2003 or 2006 and 2010, and who were followed up for 12 years.

Among the patients, 101 received conservative management (5 of whom subsequently underwent intervention after experiencing intracranial hemorrhage during the follow-up) and 103 underwent intervention. The interventions included endovascular embolization, neurosurgical excision, or stereotactic radiosurgery, alone or in combination.

The researchers found that, with a median follow-up duration of 6.9 years and 94% completing the study, patients receiving conservative management had a lower rate of progression to the primary endpoint of sustained disability or death in the first 4 years of follow-up compared with those receiving interventional treatment (36 vs 39 events; adjusted hazard ratio, 0.59; 95% confidence interval [CI], 0.35 - 0.99). However, rates were similar after the first 4 years of follow-up.

Conservative management was also associated with a lower rate of the secondary outcome of nonfatal symptomatic stroke or death that resulted from bAVM, an associated arterial aneurysm, or an intervention during the 12 years of follow-up (14 vs 38 events in the intervention group; adjusted hazard ratio, 0.37; 95% CI, 0.19 - 0.72).

Patients who had interventions were more likely to be younger, to have presented with seizure, and to have undergone catheter angiography, and were less likely to have a maximum bAVM diameter of 6 cm or larger.

The findings on the size of the bAVMs are consistent with the typical choice of patients for interventions, Dr. Salman told Medscape Medical News. "The smallest and most superficial bAVM are usually the easiest and safest to treat," he said.

Dr. Salman noted that in looking ahead, his research team's goal is to obtain even longer-term follow-up information on patient outcomes.

"We are continuing follow-up and aim to do so for our patients' entire lifetimes if we can secure the funding," he said.

"I suspect long-term follow-up will show that these findings endure, but for how long is uncertain. Even if the Kaplan-Meier survival curves cross, it will be a question of whether the difference between the areas under the curves changes, and that might take a very long time to occur."

True Risk

Neurosurgeon Kevin M. Cockroft, MD, MSc, agreed that much longer follow-up is needed to better understand the true risk to patients with unruptured brain AVMs who do and do not receive interventions.

"The findings [from this study] are not really surprising, given the relatively short period of follow-up," said Dr. Cockroft, associate professor of neurosurgery, radiology, and public health sciences and co-director of the Penn State Hershey Stroke Center at Penn State Hershey Medical Center in Pennsylvania.

"The follow-up in this study is longer than ARUBA, but still relatively short when you consider that an AVM is a life-long problem," he told Medscape Medical News.

The fact that the median follow-up was only 6.9 years, with only 10% of patients reviewed as far out as 12 years, is important, he said, and in addition to the study not being randomized, other notable limitations include a lack of details on treatment.

"We do not know whether the AVMs were actually obliterated," he noted.

"Brain AVMs are a very heterogeneous disease. There are many factors that contribute to making one AVM more likely to hemorrhage than another, and many of them are not well understood."

Studies have suggested that features of a patient or AVM that could increase the risk of bleeding include angiographic features of the AVM, such as intranidal aneurysms or venous outflow stenosis; patient symptoms, such as progressive neurologic deficits or seizures; or patient characteristics, such as younger age being associated with a greater lifetime risk, he explained. 

But the key is to make sure the risks of intervention are as low as possible, he added. 

"To this end, being treated at an experienced, high-volume center, which tends to have lower morbidity and offer more treatment options, is important, and again, this study reinforces the need for careful patient selection and evaluation at appropriate centers."

The study received support from the Medical Research Council; the Chief Scientist Office of the Scottish Government; the Stroke Association; the Netherlands Organisation for Scientific Research; and the Netherlands Heart Foundation. Dr. Cockroft disclosed that he is a consultant and a device proctor for Covidien Neurovascular. A study coauthor reported receipt of grants and personal fees from Covidien, Codman, and Microvention Terumo during the conduct of the study. No other authors have disclosed any relevant financial relationships.

JAMA. 2014;311:1661-1669. Abstract

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