Vignan Yogendrakumar, MD, MSc

European Stroke Organisation Conference
September 1–3, 2021

This session opened with a presentation by Dr. Mikhail Kalinin and the CEREHETIS Investigators on the potential neuroprotective effect of Cerebrolysin as an add-on therapy during acute reperfusion. In a pilot RCT designed to assess safety, patients were randomized to cerebrolysin + IV tPA versus IV tPA alone. The primary outcome of the study was post-treatment symptomatic hemorrhagic transformation. 117 patients were randomized to the intervention arm, while 201 were randomized to the control arm.  Symptomatic hemorrhagic transformation occurred at lower rates in those who received cerebrolysin + thrombolysis, compared to thrombolysis alone. However, functional outcomes (mRS ≤ 2) did not differ between the two groups.

This was followed by a presentation by Dr. Wayneho Kan and the American Heart Association Get With The Guidelines-Stroke group. Using the registry of 160,000+ patients, Dr. Kan presented on the outcomes of tPA use in patients who were on a NOAC versus those not on anticoagulation using propensity score overlap weighting and regression modelling. Adjusting for baseline clinical factors, the risks of symptomatic intracranial hemorrhage did not differ between the two groups (sICH: aOR, 0.88 [95%CI, 0.70-1.10]; in-hospital mortality: aOR, 0.84 [95%CI, 0.69-1.01]). Of note, the exact time of last NOAC dose was not measured in this registry, and levels of factor Xa were also not available. Based on an analysis of a smaller registry used within this study which reported time of NOAC dose, a large majority of NOAC patients treated with lysis had taken their last dose more than 24 hours prior to the stroke event.

A presentation by Dr. Valerian Altersberger and the TRISP Collaborators focused on the clinical outcomes of patients treated with thrombolysis in the extended window (4.5 to 9 hours) using real-world data from the TRISP registry. 663 patients within the registry were treated between 4.5 and 9 hours. Compared to patients treated within the first 4.5 hours (n=15,164), there were no significant differences in symptomatic intracranial hemorrhage, 3-month outcome, or mortality. The utilization of IV thrombolysis within the extended window appears to be safe using large real-world datasets. Of note, a follow-up presentation by the same group showed that patients presenting within the extended window who were not treated with the assistance of advanced imaging (MRI, CTP) had higher rates of mortality. The use of advanced imaging was associated with a shift towards favorable outcomes.

Dr. Maria Font and her collaborators at the Cat-SCR Consortium sought to understand which predictors are associated with IV thrombolysis in patients presenting with minor stroke. In a prospective population registry of 2,868 patients, the presence of an LVO and increasing NIHSS measurements (4-5 vs. 0-1) were associated with IV thrombolysis use. Expanding on the concept of treatment and minor stroke, Dr. Katharina Feil used data from the GSR and SITS registry to perform a propensity matched analysis of IV thrombolysis vs. IV thrombolysis + clot retrieval in patients presenting with LVO and minor stroke. Effectiveness, measured as an mRS 0-2 at 3-month follow-up, was similar in the two groups (67 vs. 69%), as was mortality. The authors argue that in the assessed data, thrombolysis alone appears to be comparable to thrombolysis + clot retrieval and that proper RCTs are required.

In an observational study of acute ischemic stroke patients from six centers in Italy, Dr. Michele Romoli looked at the association between fibrinogen depletion coagulopathy and hemorrhage risk after thrombolysis. In a proportion of patients, fibrinogenolysis can occur after thrombolysis and, therefore, potentially increase the risk of hemorrhage. Fibrinogen levels were measured at baseline, 2 hours, and 6 hours post-thrombolysis. Depletion was defined as a reduction below 200 mg/dl or 50% after 2 hours from thrombolysis. The primary outcome was symptomatic intracranial hemorrhage. In an analysis of 1,678 patients, fibrinogen depletion was more commonly observed in patients who exhibited symptomatic hemorrhage and was independently associated with major bleeding and symptomatic hemorrhage.

Finally, I and the EXTEND-IA TNK Investigators looked at the safety of tenecteplase dosing in LVO stroke, specifically in patients greater than 80 years of age. Compared to 0.40 mg/kg dosing, 0.25 mg/kg dosing of tenecteplase was associated with improved 90-day mRS and reduced mortality in patients >80 years. An increased number of sICH events was noted in the 0.40 mg/kg cohort. The data from this study is hypothesis-generating but shows that tenecteplase is safe to administer in older patients, and that 0.25 mg/kg may be the preferred dose.

Disclosure: Dr. Yogendrakumar presented work at this session.