Reteplase superior to Alteplase for Treatment of Acute Ischemic Stroke: NEJM

As a significant advancement in stroke treatment, a recent clinical trial published in the New England Journal of Medicine revealed that the thrombolytic agent reteplase may offer superior outcomes when compared to the current standard treatment, alteplase. This study involved over 1,400 patients and th outcomes suggests that reteplase could become a new standard in early reperfusion therapy for acute ischemic stroke.

This randomized trial involved patients who experienced an ischemic stroke within 4.5 hours of symptom onset. The participants were randomly assigned to receive either intravenous reteplase or intravenous alteplase. Reteplase was administered in two boluses of 18 mg each, 30 minutes apart, while alteplase was given at a dose of 0.9 mg per kilogram of body weight, with a maximum dose of 90 mg.

The primary efficacy outcome measured was the proportion of patients achieving an excellent functional outcome at 90 days post-treatment. This was defined as a score of 0 or 1 on the modified Rankin scale, where 0 indicates no neurologic deficit or symptoms, and 6 indicates death. Safety was primarily assessed by the incidence of symptomatic intracranial hemorrhage within 36 hours of treatment.

The study enrolled a total of 1,412 patients, with 707 receiving reteplase and 705 receiving alteplase. The results found that 79.5% of patients in the reteplase group achieved an excellent functional outcome when compared to 70.4% in the alteplase group. This marked a statistically significant improvement, with a risk ratio of 1.13 (95% CI, 1.05 to 1.21; P<0.001 for noninferiority and P=0.002 for superiority).

However, the safety profile of reteplase showed a slightly higher incidence of symptomatic intracranial hemorrhage within 36 hours, which was 2.4% in the reteplase group when compared to 2.0% in the alteplase group. The overall incidence of any intracranial hemorrhage at 90 days was higher in the reteplase group (7.7%) when compared to the alteplase group (4.9%), with a risk ratio of 1.59 (95% CI, 1.00 to 2.51). Also, adverse events were more common with reteplase which affected 91.6% of patients and 82.4% in the alteplase group (risk ratio, 1.11; 95% CI, 1.03 to 1.20).

Despite the higher rates of adverse events and intracranial hemorrhage, reteplase demonstrated a significantly better functional outcome than alteplase for patients treated within 4.5 hours of ischemic stroke onset. Overall, these findings suggest that reteplase could potentially replace alteplase as the standard agent for early reperfusion therapy, pending further research to optimize its safety profile.

Reference:

Li, S., Gu, H.-Q., Li, H., Wang, X., Jin, A., Guo, S., Lu, G., Che, F., Wang, W., Wei, Y., Wang, Y., Li, Z., Meng, X., Zhao, X., Liu, L., & Wang, Y. (2024). Reteplase versus Alteplase for Acute Ischemic Stroke. In New England Journal of Medicine. Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2400314