American Society of Hirudotherapy

Bivalirudin versus heparin during PCI in NSTEMI: individual patient data meta-analysis of large randomized trials

IPD meta-analysis published in Circulation (2023)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Meta-analysisClinical TrialsDrug DevelopmentBikdeli B et al. · Circulation, 2023

Abstract

BACKGROUND: The benefit:risk profile of bivalirudin versus heparin anticoagulation in patients with non-ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) is uncertain. Study-level meta-analyses lack granularity to provide conclusive answers. We sought to compare the outcomes of bivalirudin and heparin in patients with non-ST-segment-elevation myocardial infarction undergoing PCI. METHODS: We performed an individual patient data meta-analysis of patients with non-ST-segment-elevation myocardial infarction in all 5 trials that randomized ≥1000 patients with any myocardial infarction undergoing PCI to bivalirudin versus heparin (MATRIX [Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox], VALIDATE-SWEDEHEART [Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial], ISAR-REACT 4 [Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 4], ACUITY [Acute Catheterization and Urgent Intervention Triage Strategy], and BRIGHT [Bivalirudin in Acute Myocardial Infarction vs Heparin and GPI Plus Heparin Trial]). The primary effectiveness and safety end points were 30-day all-cause mortality and serious bleeding. RESULTS: A total of 12 155 patients were randomized: 6040 to bivalirudin (52.3% with a post-PCI bivalirudin infusion), and 6115 to heparin (53.2% with planned glycoprotein IIb/IIIa inhibitor use). Thirty-day mortality was not significantly different between bivalirudin and heparin (1.2% versus 1.1%; adjusted odds ratio, 1.24 [95% CI, 0.86-1.79]; P=0.25). Cardiac mortality, reinfarction, and stent thrombosis rates were also not significantly different. Bivalirudin reduced serious bleeding (both access site-related and non-access site-related) compared with heparin (3.3% versus 5.5%; adjusted odds ratio, 0.59; 95% CI, 0.48-0.72; P<0.0001). Outcomes were consistent regardless of use of a post-PCI bivalirudin infusion or routine lycoprotein IIb/IIIa inhibitor use with heparin and during 1-year follow-up. CONCLUSIONS: In patients with non-ST-segment-elevation myocardial infarction undergoing PCI, procedural anticoagulation with bivalirudin and heparin did not result in significantly different rates of mortality or ischemic events, including stent thrombosis and reinfarction. Bivalirudin reduced serious bleeding compared with heparin arising both from the access site and nonaccess sites.

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

Publication typeMeta-AnalysisJournal ArticleResearch Support, Non-U.S. Gov't
Indexed MeSH termsHumansHeparinNon-ST Elevated Myocardial InfarctionAnticoagulantsPercutaneous Coronary InterventionRandomized Controlled Trials as TopicHirudinsPeptide FragmentsMyocardial InfarctionHemorrhageThrombosisRecombinant Proteins

Summary

Individual patient-data meta-analysis of large bivalirudin-vs-heparin RCTs in NSTEMI PCI. Bivalirudin associated with reduced major bleeding without ischemic penalty.

Why This Matters for Hirudotherapy

This individual patient data meta-analysis of 5 large randomized trials (12,155 patients with non-ST-segment-elevation myocardial infarction undergoing PCI) compared bivalirudin with heparin for procedural anticoagulation. Bivalirudin is a synthetic peptide analog of hirudin, the direct thrombin inhibitor originally isolated from medicinal leech saliva, making these findings relevant to understanding how a leech-secretome-derived anticoagulant performs in modern practice. The study found no significant difference in 30-day mortality or ischemic events, but bivalirudin reduced serious bleeding compared with heparin (3.3% vs 5.5%; adjusted odds ratio 0.59; P<0.0001). A key caveat is that these findings pertain to an engineered pharmaceutical analog used in interventional cardiology, not to leech therapy or native hirudin itself, and the bleeding advantage must be weighed against similar ischemic outcomes.

Citation

Bivalirudin versus heparin during PCI in NSTEMI: individual patient data meta-analysis of large randomized trials.

Bikdeli B et al. · Circulation, 2023

DOI

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

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