Neurologist Christoph Diener picks his top studies from the 2024 International Stroke Conference.
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Dear colleagues, I'm Christoph Diener from the medical faculty of the University Duisburg-Essen in Germany. I would like to report on nine interesting studies that were presented at the International Stroke Conference in Phoenix, Arizona, in the beginning of February 2024. I am restricting myself to studies that were published and obviously underwent peer review.

Thrombolysis
I would like to start with thrombolysis. At the moment, we have two possibilities. One is alteplase and the other one is tenecteplase. Tenecteplase is given as a bolus, which is more convenient, but until now, the randomized studies only included patients in the 4.5-hour time window.

The TIMELESS study, published in The New England Journal of Medicine, investigated tenecteplase compared with alteplase in a time window between 4.5 and 24 hours in people who, at functional imaging, had penumbra. This study included 458 patients, of which 77% received thrombectomy. The primary endpoint was modified Rankin scale. There was no difference between alteplase and tenecteplase in terms of functional outcome and bleeding complications.

The second study, which was published in Stroke, was a dose-finding study with reteplase from China. Reteplase is cheaper than alteplase and tenecteplase and has a longer half-life. This dose-finding study included 180 patients in the 4.5-hour time window, and they compared the two doses of reteplase with alteplase. There was no difference in functional outcome or symptomatic intracranial bleeds. Therefore, clearly, we need larger phase 3 trials.

The third study was a meta-analysis published in JAMA that investigated the time window during which the addition of thrombolysis to thrombectomy is superior to thrombectomy alone. This meta-analysis included 2300 patients. Of these, 1160 received the combination of thrombolysis and thrombectomy and 1153 received only thrombectomy.

The benefit of additional thrombolysis was time dependent, and the benefit disappeared after a time interval of 2 hours and 20 minutes after the beginning of symptoms. This has clear, practical implications for this combination therapy.

Corticosteroids, Thrombectomy, Antiplatelets
My next study was published in JAMA. It's from China and investigated whether the addition of corticosteroids to thrombectomy improves the outcome. This is based on preclinical data in animals, which indicate that, for example, cortisone might prevent reperfusion injury. This study with 1680 patients showed no benefit of additional prednisone. In terms of functional outcome, there was superiority for the reduction of mortality and bleeding complications. In clinical practice, I don't think we would add prednisone or methylprednisolone in these patients.

My next study is the SELECT study. SELECT was already published and investigated thrombectomy in people with large strokes and clearly showed a benefit. The initial publication had a 90-day follow-up time and now the authors published the 1-year follow-up in these patients. They showed that, after 1 year, there was still a benefit of thrombectomy. There was no difference in mortality after 1 year. This was published in The Lancet.

What is the purpose of thrombolysis in acute ischemic stroke? The purpose is to dissolve the clot. There is also an important contribution of platelets; therefore, it is always discussed whether it makes sense to also add antiplatelet drugs to thrombolysis.

The ACTIMIS study investigated a new glycoprotein VI inhibitor, glenzocimab, which is an antibody fragment. This was a small, dose-finding, and proof-of-concept study that indicated that this combination has no increased bleeding risk. There was also no difference in benefit, but there was a trend toward lower mortality. Therefore, we need a phase 3 trial to look at this combination therapy.

Anticoagulation
Another study investigated whether anticoagulation is superior to aspirin in patients with embolic stroke of undetermined source (ESUS). We already have, unfortunately, three negative studies. Now, ARCADIA was published in JAMA. This was a study with 1100 patients. The researchers only included those who had atrial cardiopathy as an indicator of a high risk to develop atrial fibrillation.

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