Disclosure: Hans-Christoph Diener, MD, PhD, has disclosed the following relevant financial relationships:
Received honoraria for participation in clinical trials, contribution to advisory boards, or oral presentations from: Abbott; AbbVie; Boehringer Ingelheim; Lundbeck; Novartis; Orion Pharma; Teva; WebMD.
The German Research Council (DFG) supports headache research done by him.
Serves on the editorial boards of Cephalalgia, Lancet Neurology, and Drugs.
Dear colleagues, I'm Christoph Diener from the Medical Faculty of the University Duisburg-Essen in Germany. This video deals with the treatment of stroke.
I would like to start with primary prevention. We all know that direct oral anticoagulants (DOACs) are as effective as vitamin K antagonists for stroke prevention in patients with atrial fibrillation, but they have fewer bleeding complications. They still have bleeding complications, and the most frequent ones are gastrointestinal bleeds.
Abelacimab is a monoclonal antibody targeted against coagulation factor 11. The hypothesis is that this drug should be as effective as a DOAC and lead to fewer bleeding complications. This was investigated in a phase 2 trial in 1287 patients with atrial fibrillation, and the monoclonal antibody was compared with rivaroxaban.
Abelacimab had significantly fewer serious and clinically relevant nonserious bleeds, a reduction by 60% after 20 months compared with rivaroxaban, but there was also a higher risk of ischemic events. This study was published in The New England Journal of Medicine, and this requires now a large phase 3 trial where ischemic events, in particular ischemic strokes, are the primary endpoints.
Let me move to the International Stroke Conference, which happened February 5 to 7, 2025, in Los Angeles. You are all aware that systemic thrombolysis with either alteplase or tenecteplase in a 4.5-hour time window is highly effective. Currently, we have further studies on the use of these two drugs in the time window between 4.5 and 24 hours using perfusion imaging to identify penumbra.
HOPE was a study with 372 patients that compared alteplase with best medical treatment in a time window between 4.5 and 24 hours. There was a therapeutic benefit in terms of modified Rankin Scale score 0-1 after 90 days, but with a higher rate of symptomatic intracerebral hemorrhage of 3.8% for alteplase compared with 0.5% for control.
The CHABLIS-T study in China, published in Stroke, compared tenecteplase with best possible treatment in 224 patients with the same study time window between 4.5 and 24 hours, and there was no benefit in functional outcome and an increased bleeding risk. This means that, for this research question, we still need more studies.
We have now many studies that compare tenecteplase and alteplase in the 4.5-hour time window in acute ischemic stroke. A recent meta-analysis in Neurology of 11 studies and 7500 patients found a minimal benefit of tenecteplase over alteplase, with comparable mortality and symptomatic intracranial hemorrhage. The only advantage of tenecteplase is that it is given as a bolus, but it's also more expensive than alteplase.
We also know that endovascular therapy is highly effective for occlusion of proximal brain-supplying arteries, in particular in the arterial circulation. At the conference, there were three new studies presented on the potential benefit of endovascular therapy for occlusions of middle or distal arteries in the anterior circulation, including the DISTAL study with 543 patients, the ESCAPE-MeVO trial with 529 patients, and the DISCOUNT trial with 152 patients.
All three studies found no benefit of thrombectomy in this population compared with standard therapy but showed an increased rate of bleeding. Thrombectomy remains highly effective in proximal occlusions of brain-supplying arteries.
We also know that the endovascular therapy has benefits for occlusions of the vertebral and basilar arteries. This has been clearly demonstrated. A recent meta-analysis in Lancet comprised four studies on endovascular therapy with 556 patients with occlusions of the vertebral or basilar artery and compared thrombectomy with best medical treatment in 432 patients.
This showed a clear superiority for modified Rankin Scale score 0-3 with 55% for thrombectomy vs 30% for best medical treatment. There was an increased bleeding risk but still reduced mortality for thrombectomy. The greatest benefit was for proximal occlusions and in a time window of less than 12 hours.
There is now a new approach, interestingly, for intra-arterial thrombolysis after successful endovascular therapy. There was already one positive study in Spain, and at the International Stroke Conference , the ANGEL-TNK study was presented. This study randomized 255 patients and found a significant reduction in the functional outcome modified Rankin Scale score 0-1, or a better outcome after 90 days with 40.5% for intra-arterial thrombolysis vs 26.5% for best medical treatment. Mortality and symptomatic intracranial hemorrhage were not different.
There is also an important clinical question whether anticoagulation with DOACs can be resumed after intracerebral hemorrhage in patients with atrial fibrillation. The PRESTIGE-AF study, which was presented at the conference, randomized 158 intracerebral hemorrhage patients to DOACs and 161 to no DOACs. For ischemic strokes, there was a large difference in favor of the DOACs at 0.8% vs 8.6%, but there was also a significant increase in recurrent intracerebral hemorrhage, 5% for DOACs vs 0.8% for no DOACs.
Therefore, we cannot really estimate what is the real benefit compared with the risk in this population. We have still three studies ongoing, which possibly will answer this important research question.
Dear colleagues, I have discussed interesting new studies. Most of them were presented at the International Stroke Conference in Los Angeles. I'm Christoph Diener, from the Medical Faculty of the University Duisburg-Essen in Germany. Thank you very much for listening and watching.