Asundexian may not prevent second stroke after small subcortical infarct
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A secondary analysis of the phase 2 PACIFIC-STROKE trial showed that asundexian is effective for the secondary prevention of stroke in patients with stroke of atherosclerotic origin, but not those with small subcortical infarcts.
In February 2022, asundexian (Bayer) for secondary stroke prevention received fast track designation from the FDA.
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“The primary outcome of PACIFIC-STROKE was that there was no evidence of a dose-dependent effective asundexian ... asundexian 10, 20 and 50 mg was not associated with lower risk of recurrent symptomatic ischemic stroke or MRI-defined covert brain and infarction compared with placebo,” Eric E. Smith, MD, PhD, the Katthy Taylor Chair in Vascular Dementia and professor of neurology at University of Calgary, said during a presentation at the International Stroke Conference. “However, in exploratory analysis, evidence emerged that asundexian may be effective at preventing atherosclerotic stroke ... This hypothesis that asundexian prevents recurrent atherosclerotic stroke is being tested in the phase 3 OCEANIC-STROKE trial, and the main results of the PACIFIC-STROKE trial were published in the Lancet last fall.”
PACIFIC-STROKE was a phase 2 trial designed to assess the efficacy and safety of three doses of asundexian (10 mg, 20 mg and 50 mg once daily), on top of dual antiplatelet therapy and enrolled 1,808 patients (mean age, 67 years; 34% women) within 48 hours of noncardioembolic stroke symptom onset. Among the cohort, 18% had large artery atherosclerosis, 45% had small vessel occlusion and 35% had cryptogenic stroke.
As Healio previously reported, asundexian on top of DAPT successfully reduced factor XIa activity after stroke, with no excess bleeding risk.
For the secondary analysis of the phase 2 PACIFIC-STROKE trial, researchers evaluated whether the effects of asundexian after stroke varied by infarct pattern as seen on baseline MRI.
Infarcts were categorized as either single, small subcortical; multiple, large or cortical; or cortical.
The primary outcome was recurrent ischemic stroke or cover brain infarct with 6 months; the exploratory outcome was recurrent stroke or transient ischemic attack; and the secondary outcome was incident covert brain infarct at 6 months.
“The hypothesis underlying this objective is that asundexian will prevent recurrent ischemic stroke and TIA in patients presenting with larger cortical infarct on MRI, but not in patients with a small subcortical infarct on the MRI/[diffusion-weighted imaging] at baseline.” Smith said.
The patients’ baseline characteristics were well-balanced across infarct subgroups.
Smith and colleagues observed no dose-response association between asundexian for patients with single, small subcortical stroke and incidence of the primary outcome.
The researchers did observe a trend toward lower risk for the exploratory outcome among patients with one or more cortical infarcts and a trend toward lower risk for the secondary outcomes at 6 months, according to the presentation.
“Overall, the secondary MRI analysis support the hypothesis that asundexian may be effective in patients with atherosclerotic stroke, but not in patients with small subcortical stroke from small vessel occlusion,” Smith said. “The main limitation is that this is a phase 2 study. The sample size was not designed to show efficacy and that some of these analyses are post hoc and exploratory. The phase 3 OCEANIC-STROKE trial, which is now begun, will test the hypothesis that asundexian prevents recurrent ischemic stroke in patients with acute noncardioembolic ischemic stroke and evidence of cerebrovascular or systemic atherosclerosis.”
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Smith EE, et al. Late-Breaking Science Oral Abstracts I. Presented at: International Stroke Conference; Feb. 8-10, 2023; Dallas (hybrid meeting).
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