Decompressive Surgery Improves Older Stroke Patient Survival

BRASILIA, Brazil — Decompressive surgery in the treatment of middle cerebral artery (MCA) infarction significantly increased the probability of survival without the most severe grade of disability in patients older than 60 years, as has been seen in younger patients, results of a randomized trial show.

Furthermore, even though there were a small number of patients in the older group, "there is no indication that over 70 does worse," lead author Werner Hacke, MD, PhD, professor and chairman of the Department of Neurology at the University of Heidelberg, Germany, told Medscape Medical News.

Dr. Hacke presented results from the Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery II (DESTINY II) trial here at the 8th World Stroke Congress (WSC).

Deadly Infarction

MCA infarction is the deadliest subtype of ischemic brain infarction, resulting in a 70% to 80% in-hospital mortality rate when conservatively treated with mechanical ventilation and management of intracranial pressure. A pooled analysis of 3 previous randomized controlled trials, including the first DESTINY trial, showed that decompressive surgery within 48 hours reduced mortality and poor clinical outcome and improved functional outcome in patients younger than 60 years.

DESTINY II, a German multicenter, randomized, controlled clinical trial with independent endpoint assessment, was designed to see whether patients older than 60 years could also benefit. The primary endpoint was a dichotomized modified Rankin Scale (mRS) score at 6 months.

An mRS of 0 - 4 was defined as success; an mRS of 5 - 6 was defined as failure. The study was designed with interim analyses by a Data Safety and Monitoring Board (DSMB) with early stopping for futility or for efficacy.

The trial included patients aged 61 years or older with a National Institutes of Health Stroke Scale (NIHSS) of greater than 15 with a dominant hemispheric infarction or greater than 20 if the infarction was in the nondominant hemisphere. They had to have a total or subtotal MCA infarction with the territory at least partially including the basal ganglia, and they had to be able to start treatment within 48 hours of symptom onset and within 6 hours after randomization.

At a 6-month assessment of the primary endpoint, the DSMB stopped the trial after reviewing data on 80 patients. In the meantime, 32 more patients had been enrolled, and Dr. Hacke reported primary endpoint results on the 112 patients.

Baseline demographics and clinical findings were similar for the group of patients randomly assigned to the intensive care unit (ICU) alone (n = 63) and for the group receiving ICU care plus decompressive surgery (n = 49). Mean and median ages were about 70 years, half of the participants were men, 60% to 67% of infarctions were in the nondominant hemisphere, and the mean and median admission NIHSS scores were 20 to 22.

The trial prespecified an estimated absolute difference of 22.6% between the groups as a positive test of the hypothesis. "The reason we did it that way is this was a trial where you randomized dead against alive. So you don't want to...randomize a single patient more" than required, Dr. Hacke said. "So we asked for a very high statistical level."

Trial Stopped for Efficacy

When the DSMB did its 6-month interim analysis on 80 patients, it found a 24.9% absolute difference between the groups in favor of decompressive surgery. In the ICU plus decompressive surgery cohort, 20 of 49 (40.8%) patients had an mRS of 0 - 4 vs 10 of 63 (15.9%) in the ICU only cohort (P = .0038).

That makes...a number needed to treat of 4. Dr. Werner Hacke

"That makes...a number needed to treat of 4," Dr. Hacke reported. The remaining patients in each group had an mRS of 5 - 6.

A shift analysis of the mRS distribution showed that there was a significant shift of mRS scores to lower categories in the surgery group compared with the conservative management group (P < .001). The shift in the surgery group was mainly from mRS 5 - 6 to mRS 4. (mRS 5 denotes severe disability, and 6 denotes death.)

The primary endpoint by age groups showed slightly better outcomes in the surgery group for patients aged 70 years or younger (n = 28; 43% mRS 0 - 4) compared with patients older than 70 years (n = 21; 38% mRS 0 - 4). In contrast, the ICU-only cohort did worse for both age groups — 70 years or younger (n = 33) had 24% with mRS 0 - 4, and the over-70 group (n = 30) had only 7% with mRS 0 - 4.

When the DESTINY II results were compared with the pooled results of the other trials of patients younger than 60 years, the shift analyses looked fairly similar.

Dr. Hacke concluded that DESTINY II, involving patients older than 60 years, showed a positive result for the primary endpoint.

"Compared with ICU therapy only, decompressive surgery is associated with a significant decrease in the number of patients surviving with a modified Rankin [equal to or more than] 5 by 25%, mostly driven by a significantly reduced mortality by 40%," he said. As expected, the overall outcome for these older patients after malignant infarction was slightly worse (26% with mRS 5) than for patients younger than 60 years (4% with mRS 5).

In summary, Dr. Hacke said that decompressive surgery for malignant MCA infarction significantly increases the probability of survival without the most severe disability in patients older than 60 years, as was shown previously in patients younger than 60 years.

Upper Age of Benefit?

Session chair Joseph Broderick, MD, professor and chair of the Department of Neurology at the University of Cincinnati Neuroscience Institute in Ohio, commented to Medscape Medical News that DESTINY II shows that earlier results of decompressive surgery with younger patients can be extended to those aged 60 years and older.

"The question is, what's the upper age at this point in time, but at least maybe in the 60 to 70 [year] range, people may still be able to benefit in terms of particularly mortality if they have hemicraniectomy," Dr. Broderick said.

But he wondered whether a Rankin score of 4 is an acceptable outcome. It means that the patient is pretty severely affected but not bedridden and is completely care dependent.

In DESTINY II, he said "most of the difference is still driven by mortality and the [Rankin score of] 5 — people being totally bedridden and completely care dependent. And that's a question I think people have to ask themselves and have to ask families and patients what their preference would be."

But from a clinician's standpoint, the trial results mean that "we don't have to stop at age 60," he advised. "But I think any time you're making decisions, you're making decisions in the context of a given patient." Some of the factors that need to be considered are the patient's age, prestroke condition, comorbidities, stroke severity, and social context.

The study received no commercial funding. Dr. Hacke has disclosed no relevant financial relationships. Dr. Broderick was not involved in the study and has disclosed no relevant financial relationships.

8th World Stroke Congress (WSC). Abstract 866. Presented October 11, 2012.