Effect of Alteplase vs Aspirin on Functional Outcome for Patients With Acute Ischemic Stroke and Minor Nondisabling Neurologic DeficitsThe PRISMS Randomized Clinical Trial
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
A few rural hospitals in NZ have access to on-site CT and are performing stroke thrombolysis. Many other rural practioners have to make decisions about transport/destination with thrombolysis in mind for patients who present with stroke. This small RCT of patients with small, non-disabling strokes shows that there were no statistical differences between aspirin and alteplase – aspirin trending towards better outcomes. Perhaps another case of just because we can doesn’t mean we should but….
The definition of nondisabling was lose and used a NIHSS<5. This can be a heterogenous group. Also note that the trial did not recruit enough patients to be adequately powered for their expected ‘effect size’ It was terminated early by the sponsor. Also a young population with more men than women.
Practically though, in acute stroke we can’t be sure where the deficit’s are going to stop evolving. I am not sure this trial makes a difference for transfer mode/destination decisions, nor even stop discussion with the neurologist due to methodological flaws. At Waikato a NIHSS => 4 or < 4 with severe aphasia, dense homonymous hemianopia or dominant hand weakness will be considered for thrombolysis
Abstract
Importance More than half of patients with acute ischemic stroke have minor neurologic deficits (National Institutes of Health Stroke Scale [NIHSS] score of 0–5) at presentation. Although prior major trials of alteplase included patients with low NIHSS scores, few without clearly disabling deficits were enrolled.
Objective To evaluate the efficacy and safety of alteplase in patients with NIHSS scores of 0 to 5 whose deficits are not clearly disabling.
Design, Setting, and Participants The PRISMS trial was designed as a 948-patient, phase 3b, double-blind, double-placebo, multicenter randomized clinical trial of alteplase compared with aspirin for emergent stroke at 75 stroke hospital networks in the United States. Patients with acute ischemic stroke whose deficits were scored as 0 to 5 on the NIHSS and judged not clearly disabling and in whom study treatment could be initiated within 3 hours of onset were eligible and enrolled from May 30, 2014, to December 20, 2016, with final follow-up on March 22, 2017.
Interventions Participants were randomized to receive intravenous alteplase at the standard dose (0.9 mg/kg) with oral placebo (n = 156) or oral aspirin, 325 mg, with intravenous placebo (n = 157).
Main Outcomes and Measures The primary outcome was the difference in favorable functional outcome, defined as a modified Rankin Scale score of 0 or 1 at 90 days via Cochran-Mantel-Haenszel test stratified by pretreatment NIHSS score, age, and time from onset to treatment. Because of early termination of the trial, prior to unblinding or interim analyses, the plan was revised to examine the risk difference of the primary outcome by a linear model adjusted for the same factors. The primary safety end point was symptomatic intracranial hemorrhage (sICH) within 36 hours of intravenous study treatment.
Results Among 313 patients enrolled at 53 stroke networks (mean age, 62 [SD, 13] years; 144 [46%] women; median NIHSS score, 2 [interquartile range {IQR}, 1–3]; median time to treatment, 2.7 hours [IQR, 2.1–2.9]), 281 (89.8%) completed the trial. At 90 days, 122 patients (78.2%) in the alteplase group vs 128 (81.5%) in the aspirin group achieved a favorable outcome (adjusted risk difference, −1.1%; 95% CI, −9.4% to 7.3%). Five alteplase-treated patients (3.2%) vs 0 aspirin-treated patients had sICH (risk difference, 3.3%; 95% CI, 0.8%–7.4%).
Conclusions and Relevance Among patients with minor nondisabling acute ischemic stroke, treatment with alteplase vs aspirin did not increase the likelihood of favorable functional outcome at 90 days. However, the very early study termination precludes any definitive conclusions, and additional research may be warranted.