Onset to Treatment Time and Early Neurological Deterioration of Dual Antiplatelet Therapy Versus Alteplase in Minor Stroke

Abstract

Background: The ARAMIS (Antiplatelet Versus R-tPA [Recombinant Tissue Plasminogen Activator] for Acute Minor Ischemic Stroke) trial established that dual antiplatelet therapy (DAPT) is noninferior to intravenous alteplase in patients with acute minor nondisabling ischemic stroke. In this prespecified secondary analysis, we aimed to evaluate whether onset-to-treatment time (OTT) modifies the treatment effect of DAPT versus alteplase on the risk of early neurological deterioration (END).

Methods: Using the as-treated population from ARAMIS, we included patients with acute minor nondisabling ischemic stroke who were treated within 4.5 hours of symptom onset. Participants were stratified by OTT into 2 groups: 0 to 3 and 3 to 4.5 hours. The primary end point was END, defined as an increase of ≥2 points on the National Institutes of Health Stroke Scale within 24 hours. The primary safety outcome was symptomatic intracranial hemorrhage. Treatment effects were assessed using binary logistic regression and generalized linear models.

Results: Among 719 included patients, 362 (50.3%) were in the 0 to 3 hour group and 357 (49.7%) in the 3 to 4.5 hour group. DAPT was associated with a significantly lower incidence of END compared with alteplase in the 0 to 3 hour subgroup (2.6% versus 10.0%; adjusted P=0.03) but not in the 3 to 4.5 hour subgroup (6.8% versus 6.6%; P=0.79). A significant interaction was observed between OTT and treatment effect for END (P for interaction=0.04). Rates of symptomatic intracranial hemorrhage did not differ significantly between treatment groups in either OTT stratum.

Conclusions: Among patients with acute minor ischemic stroke, OTT appears to modify the effect of DAPT versus alteplase on END. Earlier initiation of DAPT may be associated with a reduced risk of END compared with alteplase.

Registration: URL: https://clinicaltrials.gov; Unique Identifier: NCT03661411.

Keywords: acute mild stroke; alteplase; dual antiplatelet therapy; early neurological deterioration; minor stroke; nondisabling stroke; onset to treatment time.