American Society of Hirudotherapy

Argatroban anticoagulation in patients with acute ischemic stroke (ARGIS-1): a randomized, placebo-controlled safety study

Research article published in Stroke (2004)

Last Updated: November 1, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Randomized controlled trialClinical LiteratureLaMonte et al. · Stroke, 2004

Abstract

BACKGROUND AND PURPOSE: Direct thrombin inhibitors, including argatroban, represent an anticoagulant class distinct from heparins. We investigated the safety of 2 levels of argatroban anticoagulation in acute ischemic stroke. METHODS: This multicenter, randomized, double-blinded, placebo-controlled study included 171 patients with acute (< or =12 hours from onset) stroke and National Institutes of Health Stroke Scale (NIHSS) scores of 5 to 22. Patients received continuous intravenous argatroban (100 microg/kg bolus) at 3 microg/kg per minute (n=59) or 1 microg/kg per minute (n=58), respectively, adjusted to target activated partial thromboplastin times (aPTTs) 2.25x and 1.75x baseline or placebo (n=54) for 5 days. The primary outcome was symptomatic intracranial hemorrhage (ICH) at 30 days. RESULTS: Baseline characteristics including neurologic deficits (median NIHSS score 9) were comparable between groups. Argatroban at mean doses of 2.7 and 1.2 microg/kg per minute increased aPTTs significantly (P<0.001), with mean aPTTs at or near target values throughout infusion. Symptomatic ICH was not significantly different between groups (high-dose argatroban, 5.1%; low-dose argatroban, 3.4%; placebo, 0%; P> or =0.18), with 3 events during argatroban infusion and 2 events > or =7 days after stopping infusion. No significant between-group differences occurred in asymptomatic ICH (7 events), major systemic hemorrhage (no event), or 90-day mortality (13.4% overall). CONCLUSIONS: In this first North American randomized, double-blinded, placebo-controlled study of direct thrombin inhibition in acute ischemic stroke, argatroban at each dose evaluated significantly prolonged aPTTs without increasing ICH or major bleeding. These results suggest that argatroban provides safe anticoagulation in acute ischemic stroke, warranting future studies powered to evaluate its efficacy and more precisely estimate event rates.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Publication typeClinical TrialJournal ArticleMulticenter StudyRandomized Controlled TrialResearch Support, Non-U.S. Gov't
Indexed MeSH termsAgedAnticoagulantsArginineDouble-Blind MethodDrug Administration ScheduleFemaleHumansIntracranial HemorrhagesMaleMiddle AgedPartial Thromboplastin TimePipecolic AcidsStrokeSulfonamidesSurvival Analysis

Summary

In 171 patients with acute ischemic stroke randomized to two argatroban doses or placebo for 5 days, symptomatic intracranial hemorrhage rates did not differ significantly between groups, and no major systemic hemorrhage occurred, suggesting safe anticoagulation at both doses.

Context

This randomized, double-blinded, placebo-controlled safety study evaluated two dose levels of argatroban (a direct thrombin inhibitor) in 171 patients with acute ischemic stroke (≤12 hours from onset) and NIHSS scores of 5–22. Argatroban at both doses significantly prolonged activated partial thromboplastin times without significantly increasing symptomatic intracranial hemorrhage (5.1% high-dose, 3.4% low-dose, 0% placebo; P≥0.18) or major systemic bleeding (no events), supporting safe anticoagulation in this population. While argatroban belongs to the same broad drug class (direct thrombin inhibitors) as hirudin, it is a synthetic small-molecule L-arginine derivative with no connection to leeches or the leech secretome.

Citation

Reference (Vancouver style)

LaMonte MP, Nash ML, Wang DZ, Woolfenden AR, Schultz J, Hursting MJ, et al. Argatroban anticoagulation in patients with acute ischemic stroke (ARGIS-1): a randomized, placebo-controlled safety study. Stroke. 2004;35(7):1677-1682. doi:10.1161/01.STR.0000131549.20581.ba. PMID: 15155959

Bibliographic details (authors, volume, pages, DOI) are taken from the PubMed record.

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