Reteplase superior vs. alteplase for lowering disability after acute ischemic stroke
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Key takeaways:
- Reteplase was superior to alteplase at reducing disability after acute ischemic stroke.
- Mortality was similar between the two drugs, despite more intracranial bleeding with reteplase.
Reteplase administered early after stroke symptom onset was superior vs. alteplase for improving 90-day disability, a speaker reported.
Despite a higher rate of intracranial bleeding in the reteplase (China Resources Angde Biotech Pharma Co.) arm of the study, mortality was not significantly different between the two groups, according to the results of the RAISE trial presented at the International Stroke Conference.
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“It is well known that reperfusion therapy is the key to the treatment of acute ischemic stroke, and intravenous thrombolysis is the cornerstone of reperfusion therapy,” Yongjun Wang, MD, of the department of neurology at the Beijing Tiantan Hospital, said during a presentation. “Since 1996, alteplase has been the major player in intravenous thrombolysis. However, the next generation of thrombolytics are more effective and convenient, such as reteplase and tenecteplase. The next generation of thrombolytics no longer need intravenous infusions for 60 minutes, just a bolus injection.
“As early as 1996, the European Medicines Agency and FDA have approved the indication of reteplase in acute MI,” Wang said. “However, to date, there is a lack of clinical evidence [of the efficacy and safety] of reteplase in acute ischemic disease.”
In a previous phase 2 study, Wang, Shuya Li, MD, of the department of neurology and department of clinical trial center at Beijing Tiantan Hospital, Capital Medical University in Beijing, and colleagues evaluated the efficacy and safety of reteplase, a non-glycosylated variant of alteplase, compared with alteplase for the treatment of acute ischemic stroke.
As Healio previously reported, as an alternative IV thrombolytic treatment, the lower-cost reteplase demonstrated a similar efficacy and safety profile as alteplase.
The present RAISE trial was a multicenter, randomized open-label, parallel-controlled, blinded outcome phase 3 trial designed to evaluate the noninferiority of reteplase compared with alteplase among 1,412 adult patients with acute ischemic stroke with an NIHS score of 4 to 25 (mean age, 63 years). Nearly one-third of trial participants were women.
Within 4.5 hours of stroke onset, participants were randomly assigned 1:1 to reteplase or alteplase.
The primary efficacy outcome was modified Rankin Scale score of 0 to 1 at 90 days. The secondary efficacy outcome was a composite of modified Rankin Scale score of 0 to 1 at 90 days; ordinal distribution of modified Rankin Scale score at 90 days; NIH Stroke Scale score of 1 or less or decrease of 4 or more points between baseline and 24 hours or 7 days after treatment; and Barthel index score of 95 or more at 90 days.
The primary safety outcome was a composite of symptomatic intracranial hemorrhage, all-cause death, major bleeding, clinically related non-massive hemorrhage; and other treatment-related adverse events at 90 days.
Wang reported that at 90 days, 80.1% of patients assigned to reteplase met the primary efficacy outcome compared with 71.1% of the alteplase arm, and that reteplase not only met noninferiority, but also reached superiority (RR = 1.13; 95% CI, 1.03-1.23). Reteplase was also reported to be noninferior for all secondary efficacy outcomes compared with alteplase.
The primary efficacy outcome did not significantly differ across any of the prespecified subgroups.
Occurrence of 90-day symptomatic intracranial hemorrhage was higher in the reteplase arm compared with the alteplase arm; however, there was no significant difference in 90-day mortality.
“Reteplase was superior to alteplase with respect to the primary efficacy outcome in patients with ischemic stroke treated within 4.5 hours of symptom onset,” Wang said. “Also, patients receiving reteplase have a higher incidence of any intracranial bleeding compared with those receiving alteplase. No significant difference was observed in the fatal safety profile. The overall finding should encourage the administration of reteplase in patients with acute ischemic stroke.”
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Wang Y, et al. Closing main event: LB 35. Presented at: International Stroke Conference; Feb. 7-9, 2024; Phoenix.
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