ISC 2020 Session: “The New Frontiers in Thrombolysis of Patients with Acute Ischemic Stroke (25th Anniversary of NINDS Trial)”

International Stroke Conference
February 19–21, 2020

Mausaminben Hathidara, MD
@mausameen

This session was divided in topics as below, each discussing different aspects associated with making decisions for tPA for extended window, proper patient selection for mild strokes and the dilemma for patients with relative contraindication, as well as thrombolysis in women with ischemic stroke.

The story from bench to bedside by Patrick Lyden

In 1995, the NINIDS trial proved the efficacy of tPA and reasonable safety. Per pilot study analysis, the dose 0.9 mg/Kg demonstrated the best efficacy, therefore, was chosen for the NINDS trial up to 3 hours from symptoms onset, which showed that patients in the treatment arm were 30% more likely to have minimal or no disability at 3 months with reasonable safety (symptomatic ICH 6.4%) for intra-cerebral. Before the NINDS trial, there were several studies that looked into tPA for acute ischemic strokes, including ECASS I and ECASS II, which did not show successful results due to different time window and dosing selection.

Thrombolysis in the extended time window by Henry Ma

Based on the NINDS trial, tPA was approved for 3 hours from symptoms onset, and the window was extended up to 4.5 hours after the ECASS III trial in 2008. However, many patients could not benefit from the treatment due to unknown time of onset such as wake up stroke, aphasia or other neurological deficits limiting the assessment. EPITHET, ECASS IV, and MR WITNESS had shown the use of MRI, MR Perfusion and CT perfusion to assess mismatch and safety of tPA in the extended window. The EXTEND trial selected patients based on CTP and MRP up to 9 hours from last known well and showed mRS (0-1) functional independence was achieved in 35% of the treatment arm group patients vs 29% in the control group with 6.2 % risk of sICH vs 0.9% in each respective group, which was similar to the NINDS trial. The WAKE UP trial included patients with unknown time of onset with the help of MRI (DWI/FLAIR mismatch) and MR Perfusion up to 4.5 hours of onset after symptoms recognition and proved efficacy in the treatment group.

Both of these trials essentially selected patients for benefit within the extended window due to unknown time of onset. The next question is, can we expand the window even further up to 24 hours, perhaps using better thrombolytics such as TNK?

Thrombolysis in patients with minor and non-disabling stroke by Negar Asdaghi

NIHSS<5 is considered mild stroke; however, despite low NIHSS, it can be disabling depending on the deficit such as aphasia, hand weakness, hemianopia, leg weakness, ataxia. The CATCH trial helped identified this patient population with high risk for deterioration and recurrence using image modalities such as CTA and CTP, as well as MRI. Up to 15% of patients with mild strokes had large vessel occlusion, and 30% of the patients had measurable perfusion deficit. Therefore, it is essential to assess these patients with mild stroke as a case-to-case scenario for their deficit whether disability producing or not and risk of recurrence before determining thrombolysis decision.

Thrombolysis in the setting of relative contraindications by Andrew Demchuk

Seizure, previous hx of stroke within 3 months, pregnancy, and any major surgery in the past 14 days are relative contraindication. However, time to time depending on the risk vs benefit ratio, physicians make treatment decisions. The questions of thrombolysis safety for patients with DOAC use within 48 hrs with the use of laboratory marker to determine level of DOAC in the system remains unanswered until further data is available. There is also a question of whether lower dose of IV tPA would have better safety and similar efficacy for patients with the active use of dual anti platelets depending on trend from retrospective studies.

Thrombolysis in women for acute ischemic stroke by Cheryl Bushnell

Retrospective studies show that women with ischemic strokes tend to have strokes at older age. Therefore, due to their poor pre-functional status and co-morbidities, stroke leads to worse outcome. Meta-analysis of a retrospective cohort suggested that women who received tPA did better compared to the other group, as well as male; however, this has not been studied in a randomized trial. It is important to test this hypothesis to understand the reason for the outcome difference between these two groups, which will provide better insight in perhaps underlying causal etiology.