COMMENTARY

2016 Stroke Research Highlights

Hans-Christoph Diener, MD, PhD

Disclosures

January 19, 2017

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Dear colleagues, I am Christoph Diener, a neurologist from the University of Essen in Germany. In this video, I would like to summarize the important studies in stroke that came out in 2016.

We had two remarkable publications on primary prevention this year. One was a burden-of-disease study published in The Lancet,[1] and the other was the case-control INTERSTROKE study with more than 27,000 patients.[2] Both studies clearly show that 90% of the risk for stroke is due to treatable risk factors. I sometimes think that we have the priorities wrong; we should contemplate much more on the primary prevention of stroke rather than on treating and secondary stroke prevention.

We had results from one randomized trial (ACT 1)[3] and a 10-year follow-up study from the CREST trial[4] comparing stenting and curative surgery with asymptomatic aortic stenosis. It is no surprise that there was no difference between stenting and surgery. Unfortunately, the most important question—whether best medical treatment would be as effective as surgery or stenting—was not answered.

Next we come to the acute treatment of ischemic stroke. The IST-3 study[5] published a subgroup analysis comparing tissue plasminogen activator alteplase (tPA) and no treatment in the time window of up to 6 hours. What the study showed, which is extremely important, is that people above the age of 80 also benefit from tPA, as did those with severe strokes and who had high blood pressure at admission. They also showed that there is an increased risk for intracerebral bleeding if people who receive tPA are pretreated with antiplatelet drugs.

The ENCHANTED trial[6] compared two doses of alteplase—the standard dose of 0.9 mg/kg body weight and the reduced dose of 0.6 mg/kg body weight. There was no major difference, but I think that one subgroup is important: The study showed that people who are pretreated with antiplatelet therapy obviously have a benefit from the low dose of tPA in terms of preventing bleeding.

The results of the DIAS-4 trial[7] were also published. Desmoteplase was used in a time window of 4.5-9 hours and compared with placebo. The study was negative.

There [was also research][8] that looked at predictors of intracranial or intracerebral bleed after tPA. The results showed that a known high load of microbleeds or severe white matter lesions increases the risk of bleeding.

We had multiple trials[9,10] that showed thrombectomy to be highly effective. The numbers needed to treat to achieve a good outcome are between 2.6 and 4. The major challenge now is to implement thrombectomy on a wide basis. There was a randomized study from Heidelberg[11] showing that the outcome is identical, regardless of whether people receive thrombectomy with sedation or global anesthesia.

When it comes to secondary stroke prevention, there was a meta-analysis[12] of the early efficacy of aspirin. It is amazing how effective aspirin is compared with no treatment or placebo in the first 2 weeks after an ischemic stroke. The risk reduction is 55%. We should start aspirin as quickly as possible.

The SOCRATES trial[13] compared ticagrelor and aspirin in people with high-risk transient ischemic attack or mild strokes. There was no benefit of ticagrelor over aspirin for the combined endpoint of stroke or myocardial infarction.

At the moment, we have two ongoing [unpublished] studies in embolic stroke of indeterminate source. These studies compare dabigatran or rivaroxaban with aspirin in this important subgroup of patients.

There was a meta-analysis[14] on the treatment of hypertension in secondary stroke prevention with 39,000 patients, [that found no significant differences in the subgroup analyses of secondary stroke prevention according to the class of the antihypertensive agent used.] Unfortunately, in all of the trials, which look at the treatment of diabetes in secondary stroke prevention, there was no positive outcome.

The last area is intracerebral bleeding. We now have data[15] on aggressive lowering of blood pressure in people who have an intracerebral bleed and high blood pressure. Unfortunately, findings did not show a benefit of aggressive lowering of blood pressure.

The good news is that we now have reversal agents for the new oral anticoagulants, and this has implications. There are now 12 cases reported from Germany who had an intracerebral bleed on dabigatran, who were all treated with the reversal agent idarucizumab. In only one patient there was a growth of the hematoma and the patient died. The mortality in this group went down to 9% compared with the usual 50% that we see in anticoagulation-induced bleeding.

Ladies and gentlemen, 2016 was an exciting year for stroke. We learned a lot about how to manage our patients.

I am Christoph Diener from the department of neurology at the University of Essen in Germany. Thank you very much for listening.

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