Reference: Khatri P, Kleindorfer DO, Devlin T, et al. Effect of Alteplase vs Aspirin on Functional Outcome for Patients With Acute Ischemic Stroke and Minor Nondisabling Neurologic DeficitsThe PRISMS Randomized Clinical Trial. JAMA. 2018;320(2):156–166. doi:10.1001/jama.2018.8496
I love me some stroke! However, nothing gets me as riled up as much as a good ole tPA for stroke study sponsored by Genentech. Look, I’m totally for thrombectomy as long as it’s done right on the right patient… I also believe in stroke centers being important to improve outcomes when caring for strokes. But haven’t we done this dance with tPA for all comers of stroke before? By my count there are 11 (if you count NINDS as 2 different studies) RCT’s of tPA for stroke. Only 2 (yes 2!) have shown benefit. So here we are now going to try to give tPA for mild non-disabling strokes? Did we forget about a little thing called brain bleeding?! Apparently so…
This was a prospective multicenter RCT of patients with NIHSS <6 and deemed to have a “non-disabling” stroke by the clinician. Patients were given either tPA at standard dose OR 325 mg of ASA. The primary outcome end point was a modified Rankin Scale (mRS) score of 0 or 1 indicative of a favorable functional outcome at 90 days. They included all comers >18 yo without an upper age limit. The only exclusions were prior disabilities. The primary safety end point was symptomatic intracranial hemorrhage (sICH), defined as any neurologic decline within 36 hours attributed to ICH. They were to enroll 948 participants, HOWEVER, the trial was stopped early and only enrolled 313 participants. The reason cited was “Study enrollment was terminated on December 20, 2016, by the sponsor…This was a financial decision based on the fact that the trial could not be completed within the allotted funds in the specified time frame.” They say the results weren’t known. However, given the drug companies past I have a hard time believing Genetech ran out of money. At least it was still published!
THE BOTTOM LINE:
So, what were the results? There was no difference in functional outcomes between the tPA group and the ASA group at 90 days (82% vs 78%). There was a difference in the amount of ICH (3.3% vs 0%). If I were Genentech I would have stopped the study also! So, what to do now? It’s still the same: talk to the patient, inform them of the harms and benefit. Let them know there is a risk of bleeding in the brain and not much difference in functional outcome if they just take the aspirin in low disability strokes. But please talk with the neurologist BEFORE you are in front of a patient. An argument at the time of tPA is not fair for patients. Make sure you and the stroke neurologists are on the same page.
Here’s a nice little infographic of the study:
Study Method: Prospective multicenter RCT of patients with NIHSS <6 and deemed to have a “non-disabling” stroke by the clinician The trial was designed to detect a 9% absolute difference in the proportion of participants with favorable outcome with 80% power. They used a 1-sided tail which gives the advantage to the study drug.
Exclusion criteria: Large vessel occlusion, standard tPA exclusions, and prior disability
Primary Outcome: The primary outcome end point was a modified Rankin Scale (mRS) score of 0 or 1 (total range, 0 [symptom free] to 6 [dead]), reflecting favorable functional outcome, evaluated at 90 days after enrollment and adjusted for age, time from symptom on- set to treatment, and baseline NIHSS score.
Primary Safety Outcome: The primary safety end point was symptomatic intracranial hemorrhage (sICH), defined as any neurologic decline within 36 hours attributed to ICH by local investigators; this definition was modified from the NINDS tPA trial definition requiring only a temporal association of decline with ICH.
Patients Enrolled: May 1, 2014, to December 20, 2016, 313 patients were enrolled,
Demographics: Mean age is 62, 77% male, other than increased elevated systolic BP in the ASA group the characteristics were similar.