European Stroke Organisation Conference
May 16–18, 2018

Aristeidis H. Katsanos, MD, PhD

Dr. Robert Hart presented the first results of the NAVIGATE ESUS trial, a randomized clinical trial (RCT) on the safety and efficacy of Rivaroxaban 15mg once daily compared to acetylsalicylic acid (ASA) 100mg in patients with embolic strokes of undetermined source (ESUS). The trial was stopped prematurely at the second interim analysis, and after randomization of a total of 7213 patients, due to the absence of significant differences between the two groups regarding the primary efficacy outcome of all recurrent stroke or systemic embolism. Moreover, a significant increase in the risk of both hemorrhagic stroke and all major bleeding events was found in the Rivaroxaban group compared to the ASA group. Although no significant differences were found in other pre-specified subgroup analyses, a subgroup analysis of patients with patent foramen ovale randomized within the NAVIGATE ESUS trial presented by Dr. Scott Kasner suggests that Rivaroxaban treatment may reduce the risk of recurrent cerebral ischemic events in this specific patient population compared to ASA.

DATAS II was a phase II RCT, presented by Dr. Ken Butcher, testing the hypothesis that 30-day Dabigatran treatment with 110 or 150mg in patients with minor acute (<72 hours) ischemic stroke (AIS) or transient ischemic attack (TIA) is not associated with increased rates of symptomatic hemorrhagic transformation compared to 30-day treatment with ASA 81mg. After successfully randomizing 305 patients, investigators found no event of symptomatic hemorrhagic transformation or parenchymal hemorrhage in either group, suggesting that Dabigatran and ASA have similar safety profiles when administered to patients with minor AIS or TIA. A phase III RCT is needed to test the potential superiority of Dabigatran in reducing the rates of early stroke recurrence compared to ASA.

Dr. Nikola Sprigg presented the results of the TICH-2 trial, a placebo-controlled RCT on the safety and efficacy of intravenous tranexamic acid infusion (1g/10 minutes followed by 1g/ 8 hours) in adult patients with acute (<8 hours from onset) spontaneous intracerebral hemorrhage. After analyzing data from a total of 2325 patients, investigators found no significant differences in the 3-month functional outcomes between the two groups. Interestingly, significant reductions in hematoma volume change and hematoma expansion were uncovered in patients allocated to tranexamic acid compared to those receiving placebo. Moreover, the tranexamic acid group had significantly higher mortality rates in the first 7 days following ictus compared to the placebo group. Patients receiving tranexamic acid were found to have no significantly fewer safety outcomes compared to the placebo group, and no increase in the venous thromboembolism rates. In the pre-specified subgroup analyses, the effect of tranexamic acid was found to be significantly more pronounced in participants with lower systolic blood pressure on admission (<170 mmHg).

ECASS 4 extend was a double-blind phase III RCT that tested the safety and efficacy of intravenous thrombolysis (IVT) administration in patients with significant penumbral mismatch on MR-imaging presenting between 4.5-9 hours after stroke onset or after arousal (wake-up stroke). Patient enrollment was closed prematurely, resulting in recruitment of a total of 119 patients. The results of the trial, suggesting lack of efficacy of IVT administration and a potential increase in mortality for the IVT treated group, were presented by Dr. Peter Ringleb.

Dr. Götz Thomalla presented the results of the WAKE-UP trial, another placebo-controlled RCT on the efficacy and safety of IVT in patients with unknown symptom onset time and DWI-FLAIR mismatch on MR-imaging. After analyzing data from a total of 503 patients investigators found that the IVT-treated group had significantly more favorable 3-month functional outcomes compared to the placebo treated group. Although the rates of symptomatic intracerebral hemorrhage were comparable between groups, IVT treated patients were found to have higher rates of parenchymal hemorrhage type 2 and a higher risk of 3-month mortality. WAKE-UP is the first positive trial relying solely on advance brain imaging for the selection of candidates for IVT administration, representing thus an effective treatment option for patients with unknown symptom onset time and especially for those who are not eligible for mechanical thrombectomy.

At the end of the session, Dr. Clay Johnston presented the long-awaited results of the POINT trial, an RCT comparing dual antiplatelet administration (600mg clopidogrel load followed by daily administration of 75mg clopidogrel and 50-325 mg ASA) compared to ASA alone for 3 months after a minor stroke or TIA. After analyzing data from 4881 participants, investigators found that dual antiplatelet therapy was associated with a significant decrease in major ischemic events compared to ASA monotherapy, particularly during the first month of treatment. However, the risk of non-intracranial major bleeding was found to be more pronounced, especially after the first month of treatment initiation, in patients receiving dual antiplatelet therapy compared to those receiving antiplatelet monotherapy. The authors concluded that dual antiplatelet administration for 3 months after a minor stroke or TIA results in the successful prevention of 15 new major ischemic events at the cost of 5 new major hemorrhagic events.