Article Impact Level: HIGH Data Quality: STRONG Summary of New England Journal of Medicine, 391(9), 810–820. https://doi.org/10.1056/NEJMoa2314779 Dr. Opeolu Adeoye et al.
Points
- This phase 3 trial evaluated the efficacy and safety of adding intravenous argatroban or eptifibatide to thrombolysis in acute ischemic stroke patients treated within three hours of symptom onset.
- Five hundred fourteen patients were randomized to receive either argatroban, eptifibatide, or placebo. The primary outcome was measured using the utility-weighted 90-day modified Rankin scale.
- The results showed no improvement in recovery with argatroban (mean score 5.2) or eptifibatide (mean score 6.3) compared to placebo (mean score 6.8), with a posterior probability indicating neither drug was superior.
- Symptomatic intracranial hemorrhage occurred at similar rates in all groups, with 4% in the argatroban group, 3% in the eptifibatide group, and 2% in the placebo group.
- The study concluded that adding argatroban or eptifibatide to thrombolysis did not improve outcomes and was associated with higher mortality, emphasizing the need for careful evaluation of adjunctive therapies in stroke management.
Summary
This phase 3, single-masked, randomized, controlled clinical trial assessed the efficacy and safety of combining intravenous thrombolysis with argatroban or eptifibatide in acute ischemic stroke patients. Conducted at 57 sites in the United States, 514 patients who had received thrombolysis within three hours of symptom onset were randomized to receive additional intravenous argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). The primary efficacy outcome was measured using the utility-weighted 90-day modified Rankin scale score, which ranges from 0 to 10, with higher scores indicating better outcomes.
The results revealed that at 90 days, the mean utility-weighted modified Rankin scale scores were 5.2±3.7 for the argatroban group, 6.3±3.2 for the eptifibatide group, and 6.8±3.0 for the placebo group. The posterior probability indicated neither argatroban (posterior mean difference -1.51±0.51, probability 0.002) nor eptifibatide (posterior mean difference -0.50±0.29, probability 0.041) was better than placebo in improving outcomes. Symptomatic intracranial hemorrhage occurred at similar rates across the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo).
The conclusion drawn from this trial is that in patients with acute ischemic stroke treated with intravenous thrombolysis within the critical three-hour window, the addition of argatroban or eptifibatide did not enhance recovery and was linked to higher mortality rates. The findings underscore the need for cautious evaluation of adjunctive therapies in stroke management to ensure they provide a clear benefit before widespread clinical implementation.
Link to the article: https://www.nejm.org/doi/10.1056/NEJMoa2314779
References 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. New England Journal of Medicine, 391(9), 810–820. https://doi.org/10.1056/NEJMoa2314779
