In study results published in JAMA, treatment with alteplase in patients with acute ischemic stroke with minor non-disabling deficits at presentation was not associated with a greater likelihood of achieving a favorable 90-day functional outcome compared with aspirin treatment. Further, alteplase may increase the risk for symptomatic intracranial hemorrhage (sICH) vs aspirin.
Patients with acute ischemic stroke with low National Institutes of Health Stroke Scale (NIHSS) scores (≤5) who were deemed eligible for treatment within 3 hours of presentation were enrolled in the study (N=313). The investigators randomly assigned patients to receive either 0.9 mg/kg intravenous alteplase plus oral placebo (n=156) or 325 mg oral aspirin plus intravenous placebo (n=157). The difference in favorable functional outcome at 90 days, as defined by a Rankin Scale score of 0 or 1, comprised the primary outcome. The primary outcome was adjusted for age, baseline NIHSS score, and time from the onset of symptoms to treatment initiation. In addition, a primary safety end point consisting of sICH <36 hours of treatment was included in the analysis.
A slightly higher percentage of patients in the aspirin group achieved a favorable functional outcome at 90 days compared with patients receiving alteplase (81.5% vs 78.2%, respectively; adjusted risk difference, −1.1%; 95% CI, −9.4% to 7.3%). No differences were observed between the two groups with regard to modified Rankin Scale (mRS) scores (odds ratio [OR] 0.81; 95% CI, 0.5-1.2) or global favorable recovery (OR 0.86; 95% CI, 0.5-1.4). A higher percentage of patients in the alteplase arm experienced sICH <36 hours of treatment compared with patients receiving aspirin (3.2% vs 0%, respectively; risk difference, 3.3%; 95% CI, 0.8%-7.4%).
The early termination, relatively short follow-up period, and the substantial percentage of patients lost to follow-up represent potential study limitations.
Despite no benefit found for alteplase in improving functional outcome at 90 days, the investigators noted that “the very early study termination precludes any definitive conclusions, and additional research may be warranted.”
Khatri P, Kleindorfer DO, Devlin T, et al; for the PRISMS Investigators. 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;320(2):156-166.