American Society of Hirudotherapy

Impact of sex on comparative outcomes of bivalirudin versus unfractionated heparin in patients with acute coronary syndromes undergoing invasive management: a pre-specified analysis of the MATRIX trial

Randomized controlled trial published in EuroIntervention (2019)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Randomized controlled trialDrug DevelopmentClinical TrialsGargiulo G et al. · EuroIntervention, 2019

Abstract

AIMS: Our aim was to assess whether bivalirudin compared with unfractionated heparin (UFH) is associated with consistent outcomes in males and females with acute coronary syndrome (ACS) undergoing invasive management. METHODS AND RESULTS: In the MATRIX programme, 7,213 patients were randomised to bivalirudin or UFH. Patients in the bivalirudin group were subsequently randomly assigned to receive or not a post-PCI bivalirudin infusion. The 30-day co-primary outcomes were major adverse cardiovascular events (MACE), defined as death, myocardial infarction, or stroke, and net adverse clinical events (NACE), defined as MACE or major bleeding. The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target vessel revascularisation (TVR), definite stent thrombosis (ST), or NACE. The rate of MACE was not significantly lower with bivalirudin than with heparin in male (rate ratio [RR] 0.90, 95% confidence interval [CI]: 0.75-1.07; p=0.22) and female patients (RR 1.06, 95% CI: 0.80-1.40; p=0.67) without significant interaction (pint=0.31), nor was the rate of NACE (males: RR 0.85, 95% CI: 0.72-1.01; p=0.07; females: RR 0.98, 95% CI: 0.76-1.28; p=0.91; pint=0.38). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent TVR, definite ST, or NACE (males: RR 0.84, 95% CI: 0.66-1.07; p=0.15; females: RR 1.06, 95% CI: 0.74-1.53; p=0.74; pint=0.28). CONCLUSIONS: In ACS patients, the rates of MACE and NACE were not significantly lower with bivalirudin than with UFH in both sexes. The rate of the composite of urgent TVR, definite ST, or NACE was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion in both sexes.

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

Publication typeComparative StudyJournal ArticleRandomized Controlled Trial
Indexed MeSH termsAcute Coronary SyndromeAnticoagulantsAntithrombinsFemaleHeparinHirudinsHumansMalePeptide FragmentsPercutaneous Coronary InterventionRecombinant ProteinsTreatment Outcome

Summary

Our aim was to assess whether bivalirudin compared with unfractionated heparin (UFH) is associated with consistent outcomes in males and females with acute coronary syndrome (ACS) undergoing invasive management.

Why This Matters for Hirudotherapy

This pre-specified subgroup analysis of the MATRIX randomized trial (n=7,213) evaluated whether bivalirudin versus unfractionated heparin produced consistent outcomes across male and female ACS patients undergoing invasive management. Neither MACE nor NACE rates were significantly lower with bivalirudin in either sex, and there was no significant sex-by-treatment interaction; post-PCI bivalirudin infusion also showed no significant benefit in either sex. The ASH relevance is indirect: bivalirudin is a hirudin-derived direct thrombin inhibitor, and large-scale cardiovascular outcome data on such agents helps inform understanding of the leech-inspired anticoagulant drug class. However, this study does not involve leech therapy or leech secretome preparations, and the absence of significant benefit for bivalirudin over heparin in this population is a noteworthy finding that tempers enthusiasm for the drug class in this specific clinical context.

Citation

Impact of sex on comparative outcomes of bivalirudin versus unfractionated heparin in patients with acute coronary syndromes undergoing invasive management: a pre-specified analysis of the MATRIX trial.

Gargiulo G et al. · EuroIntervention, 2019

Added to ASH library: May 27, 2026 · Site last updated: June 18, 2026

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