Alteplase Improved Functional Outcomes When Administered 4.5 to 24 Hours After Posterior Circulation Stroke Onset

Results of the Chinese, phase 3 EXPECTS clinical trial (NCT0549476) suggest that Activase treatment (alteplase; Genentech, South San Francisco, CA) may be safe and effective when administered 4.5 to 24 hours after the onset of posterior circulation ischemic stroke. Study participants treated with Activase showed significant improvements in functional outcomes relative to standard medical treatment, with similar incidence of symptomatic intracranial hemorrhage within 36 hours. The findings of the EXPECTS study were published in the New England Journal of Medicine.

EXPECTS included 234 adult participants who had posterior circulation ischemic stroke and no planned thrombectomy. Participants were randomized to receive either Alteplase 0.9 mg/kg (n=117) or standard medical treatment (n=117) initiated between 4.5 and 24 hours after stroke symptom onset. Measured at 90 days, the primary end point of the study was functional independence, defined as a modified Rankin scale (mRS) score of 0 to 2.

At 90 days, a significantly higher percentage of participants who received Alteplase achieved functional independence compared with those who received standard medical treatment (89.6% vs 72.6%; adjusted risk ratio, 1.16; 95% CI, 1.03 to 1.30; P=.01).

In terms of key secondary end points:

• Within 36 hours of treatment initiation, the incidence of symptomatic intracranial hemorrhage was similar for participants who received Activase (1.7%) and those who received standard medical treatment (0.9%).
• At 90 days, 8.5% of participants in the standard medical treatment group had died compared with 5.2% in the Activase group.

The study authors highlighted a few limitations in their study design, noting that most participants had experienced a mild stroke and that more participants in the Activase group switched to standard medical treatment than the inverse. Additionally, the study authors found that fewer Activase-treated participants experienced large-artery atherosclerosis than those who received standard medical treatment, identifying an area for future investigation.