American Society of Hirudotherapy

Clinical outcomes after TAVR with heparin or bivalirudin as periprocedural anticoagulation in patients with and without peripheral arterial disease: results from the BRAVO-3 randomized trial

Randomized trial subanalysis published in Catheterization and Cardiovascular Interventions (2019)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Research reportClinical LiteratureDrug DevelopmentZilberszac R et al. · Catheterization and cardiovascular interventions, 2020

Abstract

OBJECTIVES: This study sought to investigate the clinical outcomes of patients with and without peripheral artery disease (PAD) in the BRAVO-3 trial with respect to the effect of bivalirudin versus unfractionated heparin (UFH). BACKGROUND: PAD is found frequently in patients undergoing transcatheter aortic valve replacement (TAVR) and is reported to confer an increased risk of adverse events. It is unknown whether patients with and without PAD may demonstrate a differential response to bivalirudin versus UFH. METHODS: BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or cerebrovascular accidents (CVA). Net adverse cardiovascular events (NACE) were a composite of major bleeding or MACE. RESULTS: The total cohort included 119 patients with PAD. Vascular complications occurred significantly more frequently in patients with PAD both in-hospital (25.2 vs. 16.7%; OR 1.68) and at 30 days (29.4 vs. 17.3%; OR 1.99). No significant differences were observed regarding mortality, NACE, MACE, major bleeding or CVA with bivalirudin versus UFH among patients with or without PAD. In patients with PAD, bivalirudin was associated with an increased risk of minor vascular complications at 30 days. CONCLUSIONS: Patients with PAD undergoing transfemoral TAVR did not exhibit an increased risk of any major adverse events, according to the procedural anticoagulant randomization. However, patients treated with Bivalirudin had significantly higher rates of minor vascular complications.

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

Publication typeComparative StudyJournal ArticleMulticenter Study
Indexed MeSH termsAgedAged, 80 and overAnticoagulantsAntithrombinsAortic Valve StenosisCatheterization, PeripheralCerebrovascular DisordersEuropeFemaleFemoral ArteryHemorrhageHeparinHirudinsHospital MortalityHumansMaleMyocardial InfarctionNorth AmericaPeptide FragmentsPeripheral Arterial DiseasePuncturesRandomized Controlled Trials as TopicRecombinant ProteinsRetrospective StudiesRisk AssessmentRisk FactorsTime FactorsTranscatheter Aortic Valve ReplacementTreatment Outcome

Summary

BRAVO-3 subanalysis of 802 TAVR patients (119 with peripheral arterial disease) compared bivalirudin with heparin. PAD patients had more vascular complications overall, and among PAD patients bivalirudin increased minor vascular complications, with no differences in major adverse events by anticoagulant.

Why This Matters for Hirudotherapy

This randomized multicenter trial (BRAVO-3, n=802) compared bivalirudin versus unfractionated heparin as periprocedural anticoagulation during transfemoral transcatheter aortic valve replacement, analyzing outcomes in patients with and without peripheral artery disease. The abstract reports no significant differences in mortality, major adverse cardiovascular events, major bleeding, or cerebrovascular accidents between bivalirudin and heparin among patients with or without PAD, though bivalirudin was associated with higher rates of minor vascular complications in PAD patients. The abstract does not mention leeches, hirudin, leech saliva, or any leech-derived origin for bivalirudin, and does not describe the study as a secondary analysis. Bivalirudin (formerly Hirulog) is a synthetic peptide anticoagulant designed partly on the C-terminal sequence of hirudin, the anticoagulant of the medicinal leech (Maraganore et al., 1990); this paper studies the drug, not leech therapy.

Citation

Reference (Vancouver style)

Zilberszac R, Chandiramani R, Hengstenberg C, Sartori S, Cao D, Chandrasekhar J, et al. Clinical outcomes after TAVR with heparin or bivalirudin as periprocedural anticoagulation in patients with and without peripheral arterial disease: results from the BRAVO-3 randomized trial. Catheter Cardiovasc Interv. 2020;96(3):E377-E386. doi:10.1002/ccd.28642. PMID: 31808295

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

DOIPubMed

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

This website provides educational information and does not constitute medical advice, diagnosis, or treatment recommendations. Medicinal leech therapy carries clinically meaningful risks and should be performed only by qualified clinicians under institutionally approved protocols. FDA 510(k) clearance for medicinal leeches is limited to specific indications; investigational and off-label discussions are labeled accordingly. For patient-specific guidance, consult a qualified healthcare provider.