Written by Clay Smith
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Not surprisingly, patients with mild, non-disabling stroke did not benefit from receiving alteplase over aspirin. If anything, the trend favored aspirin. Five patients (3.2%) who received alteplase had intracranial hemorrhage (see example figure).
Why does this matter?
I’m not even going to get into the tPA debate here. Most prior lytic studies excluded patients with mild neurological deficits from getting thrombolytic agents. Why give a potentially dangerous drug and risk a major bleed when the stroke is not disabling? Why indeed?
Remind me why this was a good idea?
This was a RCT of 313 patients with mild, non-disabling stroke, NIHSS 0-5. The original study protocol called for an enrollment of 948. The study was funded by Genentech and, “was terminated due to slow enrollment.” Authors noted, “This was a financial decision,” by Genentech and that, “The academic members of the steering committee recommended against termination but accepted this financial decision by the sponsor.”
Patients were randomized to receive standard dose alteplase (tPA) and oral placebo or aspirin 325mg orally and IV placebo. They found no statistical difference in the primary outcome (modified Rankin Scale score 0-1) at 90 days, though the trend favored the aspirin group; 78.2% of patients had a good outcome in the alteplase group vs 81.5% in the aspirin group. Again, this was not statistically significant. There was a statistically significant increased risk of symptomatic intracranial hemorrhage in the alteplase group, 3.2% (5 patients) vs zero in the aspirin group. Serious adverse events were double in the alteplase group vs aspirin: 26% vs 13%. The authors concluded, “the very early study termination precludes any definitive conclusions, and additional research may be warranted.”
Really? These patients had mild strokes; half got alteplase anyway, and five of them had a head bleed as a result. Can anyone tell me why this study was a good idea? It raises serious questions about the safety of “additional research.” My vote is a firm NO.
An example of the risk of tPA for mild stroke from the JAMA supplemental content.
Source
Effect of Alteplase vs Aspirin on Functional Outcome for Patients With Acute Ischemic Stroke and Minor Nondisabling Neurologic Deficits: The PRISMS Randomized Clinical Trial. JAMA. 2018 Jul 10;320(2):156-166. doi: 10.1001/jama.2018.8496.
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Reviewed by Thomas Davis
I would be very careful with the methodology of this paper. If you do not believe NINDS due to methodologic failings, you should have the same reservations about this trial. Questions in patient selection, unbalanced groups, incomplete 90 day follow up, imputation of outcomes… Not to mention termination with only 1/3rd of patients enrolled. This paper should not be the crutch to base a non-tPA argument for the NIHSS 4 patient.
It seems like it would be hard to now say there is equipoise for future study of lytics in mild, non-disabling stroke after this study.