University Times

Deaths, strokes halt stent study

A nationwide clinical trial involving 451 patients at high risk for a second stroke has found that those who received intensive medical treatment had fewer strokes and deaths than patients who received a brain stent in addition to the medical treatment.

Investigators from UPMC and 49 other sites around the country published the results recently in the online edition of the New England Journal of Medicine.

New enrollment in the study was stopped in April because early data showed significantly more strokes and deaths in the stented patients at the 30-day mark compared to those who received the medical management alone.

Researchers involved in the NIH Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study looked at whether patients had a second stroke or died within 30 days of enrollment, or had a stroke in the same area of the brain from 30 days to the end of follow-up. Investigators had hypothesized that compared to intensive medical therapy alone, the addition of an intracranial stenting system would decrease the risk of a stroke or death by 35 percent over two years.

Instead they found that 14.7 percent of patients (33) in the stenting group experienced a stroke or died within the first 30 days after enrollment, compared with 5.8 percent (13) of patients treated with medical therapy alone. There were five stroke-related deaths within 30 days, all in the stenting group, and one non-stroke-related death in the medical management group.

During a follow-up period of just less than one year, 20.5 percent of patients in the stenting group and 11.5 percent of patients in the medical group had a stroke or death, or a stroke in the same area of the brain beyond 30 days, a highly significant difference in favor of the patients in the study’s medical group.

Based on these data, the Data and Safety Monitoring Board recommended that the National Institute of Neurological Disorders and Stroke stop enrollment, and the NIH issued a clinical alert. All patients will continue to be followed for two years to determine the long-term effects of both interventions.

One possible explanation for the higher stroke rate in the group that got a stent, which self-expands to widen a major artery in the brain to facilitate blood flow, is that patients who have had recent stroke symptoms sometimes have unstable plaque in their arteries that the stent could have dislodged, researchers suggested. The study device, the Gateway-Wingspan intracranial angioplasty and stenting system, is the only system currently approved by the U.S. Food and Drug Administration (FDA) for certain high-risk stroke patients. The authors noted that although similar stenting systems that do not have FDA approval are being used in clinical practice, they did not evaluate those devices in this study.

The researchers also emphasized that the study participants were in the highest risk category, with blockage or narrowing of arteries of 70-99 percent. Stroke patients with moderate cerebral arterial blockage (50-69 percent) were excluded because their risk of stroke is low with usual medical management, and researchers thought this group would be unlikely to benefit from stenting.

Tudor G. Jovin, director of the UPMC Stroke Institute and co-principal investigator at the UPMC study site, said, “One of the most important observations from SAMMPRIS is that in keeping with findings from multiple other cardiovascular trials, the great progress in terms of event reduction achieved in the past decade by medical therapy also applies to symptomatic intracranial atherosclerotic disease. Therefore, for patients who met SAMMPRIS eligibility criteria, we found that aggressive medical therapy regimens, similar to those used in SAMMPRIS, were superior to angioplasty and stenting with the Gateway balloon and Wingspan stent system.”

Participants’ intensive medical management included a daily dosage of 325 milligrams of aspirin and 75 milligrams a day of clopidogrel (used to prevent blood clots) for 90 days, and aggressive management of key stroke risk factors — high blood pressure and high levels of low density lipoprotein (LDL), the unhealthy form of cholesterol.

All patients also participated in a lifestyle modification program focused on quitting smoking, increasing exercise and controlling diabetes and cholesterol.

Vivek K. Reddy, a faculty member in neurology and medical director for hospital information technology, also is a co-principal investigator at the UPMC study site.

The National Institute of Neurological Disorders and Stroke funded the trial.

Some grieving kids need extra help

School of Medicine researchers reported in the September issue of the Archives of General Psychiatry that 40 percent of children who lose a parent to sudden death will require intervention to prevent prolonged grief and possible depression.

Lead author Nadine M. Melhem, a psychiatry faculty member, said, “The death of a parent is consistently rated as one of the most stressful events a child can experience; however, little is known about the course of grief and its effects on children. With our research, we are hoping to gain greater understanding of grief reactions so that we can better design treatments to relieve the burden of grief in bereaved children.”

Building upon their prior findings, the researchers studied 182 children ages 7-18 whose parent died from suicide, accident or sudden natural deaths. They found that more than half of the children were able to cope with their grief within one year of the loss of their parent. However, the course of grief was shown to be more difficult for some children, with 30 percent showing a more gradual easing of their symptoms and about 10 percent displaying high and prolonged grief for nearly three years after their parents died. Those children with prolonged grief reaction also showed increased incidents of depression.

The researchers previously noted increased rates of psychiatric disorders in the parents prior to their deaths, not only among those who died from suicide but also those who died from accident and sudden natural death, suggesting a pre-existing vulnerability in their children that puts them at higher risk for adverse psychiatric outcomes following their deaths.

The research team also examined the wellbeing of the children’s surviving caregivers, as previous research consistently has shown that it is a significant predictor of the children’s overall wellbeing. They found that the combination of complicated grief in the surviving parent and in the child were particularly strong in predicting depression in children up to three years after the death.

“These findings have important clinical implications for intervention and prevention efforts,” noted Melhem. “We believe it is imperative to assess the surviving parent and intervene when appropriate to improve the outcome of parentally bereaved children. Treatment of prolonged grief in children may require interventions that are family focused, rather than individually focused. Preventive interventions should target not only the 10 percent of bereaved children with prolonged grief, but also the 30 percent with increased grief reactions as they also showed increased incidents of depression.”

Pitt co-authors of the study included David A. Brent, Giovanna Porta and Monica Walker Payne, all of the Department of Psychiatry.

This study was supported by the National Institute of Mental Health and the American Foundation for Suicide Prevention.

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The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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