DESTINY II: Benefit of Surgery for Stroke With Swelling

March 24, 2014

Final results of the DESTINY II study confirm that decompressive hemicraniectomy increased survival without severe disability among patients 61 years of age or older with brain swelling after a malignant middle-cerebral-artery stroke.

The results were published in the March 20 issue of the New England Journal of Medicine. The main study findings were previously presented, and reported by Medscape Medical News, at the European Stroke Conference in London last June.

"The results are very clear. There is a huge reduction in mortality — close to half — with surgery," senior author, Werner Hacke, MD, PhD, Department of Neurology, University of Heidelberg, Germany, said in an interview with Medscape Medical News. "And there is an absolute 25% reduction in the primary outcome — death or very severe disability (modified Rankin scale [mRS] score 5). So you are more likely to survive with surgery. You are more likely to survive and be left in mRS score 3 or 4 with surgery. And although there are numerically more patients in mRS score 5, that is because the rest of the control group is dead."

He added: "If you survive, then the distribution between mRS scores 3, 4 and 5 is very similar in both groups. The number of patients who survive is increased in all mRS scores. If anything, there is slightly better outcome in the surgery group, with more chance of being in mRS 4 than 5. But the major difference is that you are much more likely to survive if you have surgery."

In an accompanying editorial, Allan Ropper, MD, Brigham and Women's Hospital, Boston, Massachusetts, notes that about half of surviving patients are left with an mRS score of 4 and about a third with a score of 5.

Dr. Werner Hacke

"These outcomes, while bracing, are about the same with or without the operation, and it can be stated that hemicraniectomy does not increase the number of disabled patients," he writes.


For the DESTINY II study (Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery II), 112 patients (median age, 70 years) with brain edema following malignant middle-cerebral-artery infarction were assigned to conservative treatment in the intensive care unit (the control group; n = 63) or hemicraniectomy (the temporary removal of a large part of the skull to relieve pressure on the brain) (surgery group; n = 49).

The primary endpoint was survival without severe disability, defined by a score of 0 to 4 on the mRS. This occurred in 38% of the hemicraniectomy group compared with 18% of the control group (odds ratio, 2.91; 95% confidence interval, 1.06 - 7.49; P = .04). Mortality was reduced by 43% in the surgery group.

When the study was previously presented at the stroke conference, the discussion centered on whether saving a life for the patient to be left with an mRS score of 5 was a good outcome or not. The exact numbers in each mRS category, together with secondary outcomes — now published in the New England Journal of Medicine paper — enable a more informed view.

Table 1. mRS Scores at 6 Months

mRS Score Surgery (%) Control (%)
3 7 3
4 32 15
5 28 13
6 (death) 33 70


Table 2. mRS Scores at 12 Months

mRS Score Surgery (%) Control (%)
3 6 5
4 32 11
5 19 8
6 (death) 43 76


Professor Hacke also pointed out that quality-of-life scores in survivors did not differ between the 2 groups. "A strict intention-to-teat analysis for quality of life was massively positive in favor of surgery as you have to assign a value to those who are dead. And they obviously have no quality of life. But if you only look at survivors, there is not much difference."

Table 3. Quality-of-Life Results

Measure Surgery, n/n (%) Control, n/n (%)
SF-36 score    
    Mental component    
      51 to 100 10/25 (40) 6/12 (50)
      26 to 50 14/25 (56) 6/12 (50)
      0 to 25 1/25 (4) 0/12 (0)
    Physical component    
      26 to 100 11/25 (44) 5/12 (42)
      0 to 25 14/25 (56) 7/12 (58)
Hamilton Depression Rating Scale score    
    0 to 19 18/18 (100) 5/6 (83)
   20 to 52 0/18 (0) 1/6 (17)
EQ-SD score    
    51 to 100 6/22 (27) 2/10 (20)
    25 to 50 10/22 (45) 5/10 (50)
    0 to 25 6/22 (27) 3/10 (30)

Short Form-36 (SF-36) scores: higher scores show better well-being. Hamilton Depression Rating Scale: higher scores indicate greater severity of depression, and scores higher than 19 indicate severe depression. EQ-SD (EuroQoL Group 5-Dimension Self-Report Questionnaire): quality of life scale from 0 (worst) to 100 (best).


Professor Hacke noted that they asked patients or relatives of those who survived if, knowing the outcome, they would agree to enter this trial again.

"We received answers from two thirds of the survivors and almost 80% said yes," he notes. "It was the same for both groups. That is telling us something. The outcome we may consider bad is acceptable to the patients and the relatives of the patients."

He added: "It all depends on what the individual patient and family wants and what they are ready to accept. We don't ask patients or families to make this choice after a severe traumatic brain injury or if someone is resuscitated after a massive heart attack. In both these cases, outcomes are poor but we still do everything possible to save their lives. We should do the same thing for stroke patients. The only difference with these patients is that they may be older. This study shows that we can help patients who otherwise die to survive and in a really massive way."

We've had these numbers for about a year now and when they are presented to patients and relatives in my experience most of the time they opt for the surgery. Dr. Werner Hacke

He says this study has given doctors the numbers needed to communicate the risks to relatives more exactly.

"We can say there is an 80% chance of death without surgery and we can lower this by 40% with surgery. With both approaches, the patients who survive will be left with disability, but there is a good chance that it will not be the most severe disability. We've had these numbers for about a year now and when they are presented to patients and relatives in my experience most of the time they opt for the surgery."

Should Economics Be Considered?

On the issue of cost, Professor Hacke says that survival with disability will always be more expensive to society than death. "The cheapest solution is always death. But if we allow patients with other diseases to survive we should allow stroke patients to survive too. The argument may be that these patients are older, but I would say that we do hip replacements and primary angioplasty on 90-year-olds. We should also consider treatment for stroke. There is nothing peculiar about the brain."

Dr. Ropper agrees with this view. "I would be very uncomfortable if economics were allowed to play any part in this decision. It is not too far away from what the Nazis were doing if doctors are asked to decide who should and should not be cared for. That is a very dangerous course. This is a decision for each individual family to make," he commented to Medscape Medical News.

"The DESTINY II investigators have helped us enormously as we now have the numbers to allow families of these patients to make decisions," he added. "But any patient who has a stroke large enough to cause swelling is going to be left disabled, and some quite severely. The surgery doesn't change that. But it does significantly reduce the additional harm and mortality caused by the swelling.

"To almost halve mortality rate is quite something. The societal view is that we don't let go of a patient just because they have a stroke. Therefore if they have a complication that can be reversed, I believe it is reasonable to try to do so."

But now we have numbers for the over 60s who are the core group affected, and in that aspect this study is a real tour de force. Dr. Allan Ropper

Dr. Ropper compared the brain swelling in stroke patients to the development of pneumonia or a blood clot. "Families make decisions whether to treat these conditions or not. Until now we only had data for hemicraniectomy for brain swelling after a stroke on the younger age group. But now we have numbers for the over 60s who are the core group affected and in that aspect this study is a real tour de force."

"This procedure is obviously life-saving, but the paralysis as the result of the very large stroke will remain. Each family needs to make the decision individually as to what that patient would want. This will depend to some extent on the patient's status before the stroke."

In his editorial, Dr. Ropper concludes that: "People seem content to escape with their lives. Such is the inconclusive nature of statistical outcomes applied to this primal and ultimate choice."

DESTINY II was supported by a grant from the Deutsche Forschungsgemeinschaft. The authors have disclosed no relevant financial relationships.

N Engl J Med 2014;370:1091-1100. Abstract Editorial


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