Combining Argatroban or Eptifibatide with Thrombolysis Does Not Benefit Stroke Patients: NEJM

A recent clinical trial published in the New England Journal of Medicine revealed that the addition of argatroban, an anticoagulant, or eptifibatide, an antiplatelet agent, to standard intravenous thrombolysis for acute ischemic stroke does not improve outcomes and may increase mortality. The trial was conducted across 57 sites in the US to assess whether combining these agents with thrombolysis could reduce post-stroke disability and improve recovery in stroke patients.

The study included a total of 514 patients who had received intravenous thrombolysis (with 70% receiving alteplase and 30% receiving tenecteplase) within 3 hours of stroke onset. The participants were randomly assigned to receive either argatroban, eptifibatide or a placebo within 75 minutes of starting thrombolysis. This study assessed both the efficacy and safety of the adjunctive treatments, using the utility-weighted 90-day modified Rankin scale (mRS) score to measure disability and symptomatic intracranial hemorrhage to assess safety.

The primary efficacy outcome was the mRS score at 90 days which ranges from 0 (no symptoms) to 10 (severe disability), with higher scores by indicating better functional outcomes. The placebo group had a mean score of 6.8 by suggesting relatively better outcomes than both the argatroban (mean score of 5.2) and eptifibatide groups (mean score of 6.3). This indicates that neither argatroban nor eptifibatide significantly improved recovery after stroke when compared to placebo.

The incidence of symptomatic intracranial hemorrhage was low across all groups, with no significant differences (4% in the argatroban group, 3% in the eptifibatide group, and 2% in the placebo group). The patients in the argatroban group had a mortality rate of 24%, double that of the eptifibatide group (12%) and triple that of the placebo group (8%).

The findings suggest that the addition of these agents to standard thrombolysis therapy does not provide added benefit in reducing disability and might pose increased risks. The posterior probability that argatroban improved outcomes when compared to placebo was only 0.002, and for eptifibatide, it was 0.041 which were both far from showing a significant benefit.

Overall, while intravenous thrombolysis remains a standard treatment for acute ischemic stroke, this trial demonstrates that adding argatroban or eptifibatide to the regimen does not improve recovery and may be associated with higher mortality rates. Further research is imperative to explore alternative strategies for improving outcomes in stroke patients without increasing risks.

Reference:

Adeoye, O., Broderick, J., Derdeyn, C. P., Grotta, J. C., Barsan, W., Bentho, O., Berry, S., Concha, M., Davis, I., Demel, S., Elm, J., Gentile, N., Graves, T., Hoffman, M., Huang, J., Ingles, J., Janis, S., Jasne, A. S., Khatri, P., … Barreto, A. D. (2024). Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke. In New England Journal of Medicine (Vol. 391, Issue 9, pp. 810–820). Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2314779