Efficacy and Safety of Reteplase Versus Alteplase in Acute Ischemic Stroke Based on Fibrinogen Levels: The RAISE Trial Subgroup
Research article published in Journal of the American Heart Association (2026)
Abstract
BACKGROUND: The effects of intravenous thrombolytic agents on fibrinogen differ due to structural differences among the agents. Using data from the RAISE (Reteplase Versus Alteplase for Acute Ischemic Stroke) trial, we aimed to investigate the impact of differences in baseline plasma fibrinogen levels on the efficacy and safety of reteplase versus alteplase within 4.5 hours of acute ischemic stroke symptom onset. METHODS: This post hoc subgroup analysis of the multicenter RAISE trial categorized participants by baseline fibrinogen levels: low (<2 g/L), normal (2-4 g/L), and high (>4 g/L). The primary efficacy outcome was excellent functional outcome at 90 days (modified Rankin scale score of 0 or 1). The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours. RESULTS: A total of 1373 patients with acute ischemic stroke were included. Ninety-two in the low fibrinogen group (<2 g/L), 1178 in the normal fibrinogen group (2-4 g/L), and 103 in the high fibrinogen group (>4 g/L). Adjusted risk ratios of primary efficacy outcome were 1.13 (95% CI, 0.97-1.32) for the low fibrinogen group, 1.13 (95% CI, 1.04-1.23) for the normal fibrinogen group, and 1.09 (95% CI, 0.84-1.42) for the high fibrinogen group. The primary safety outcome showed no difference between reteplase and alteplase in the 3 fibrinogen subgroups. CONCLUSIONS: Among patients with acute ischemic stroke who were treated with either reteplase or alteplase within 4.5 hours after symptom onset, there was no difference observed in the relative efficacy and safety between the 2 groups across the 3 fibrinogen subgroups. However, these findings should be interpreted cautiously and require validation in larger, adequately powered prospective studies. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05295173.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Peer-reviewed research on safety and infection-control considerations relevant to leech therapy and anticoagulation. Indexed in PubMed and verified against the NCBI record.
Why This Matters for Hirudotherapy
This post hoc subgroup analysis of the multicenter RAISE trial examined whether baseline plasma fibrinogen levels (<2, 2–4, >4 g/L) influenced the relative efficacy and safety of reteplase versus alteplase in 1,373 patients treated within 4.5 hours of acute ischemic stroke onset. While reteplase and alteplase are fibrinolytic agents whose mechanism differs from that of leech-derived hirudin (a direct thrombin inhibitor), the study holds indirect relevance for hirudotherapy by illustrating how baseline coagulation-related biomarkers can modulate antithrombotic treatment outcomes — a consideration when evaluating leech-secretome-based approaches to thrombotic conditions. The study found no difference in relative efficacy or safety between the two agents across the three fibrinogen subgroups. As a post hoc subgroup analysis, these findings are exploratory and, as the authors note, require validation in larger, adequately powered prospective studies.
Citation
Efficacy and Safety of Reteplase Versus Alteplase in Acute Ischemic Stroke Based on Fibrinogen Levels: The RAISE Trial Subgroup.
Wang et al. · Journal of the American Heart Association, 2026
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