Potential mechanism of acute stent thrombosis with bivalirudin following percutaneous coronary intervention in acute coronary syndromes
Randomized controlled trial published in International journal of cardiology (2016)
Abstract
BACKGROUND: Clinical trials have demonstrated an excess of acute stent thrombosis (AST) in acute coronary syndromes patients (ACS) undergoing percutaneous coronary intervention (PCI) with bivalirudin compared to heparin. We aimed to investigate the potential mechanisms responsible for thrombus formation under bivalirudin. METHODS: We compared heparin and bivalirudin during PCI for ACS in a prospective monocentre randomized study. Twenty patients were included after coronary angiography and received a loading dose (LD) of 180mg of ticagrelor at the time of PCI. They were randomly assigned to heparin (70UI/kg) intra-venous (IV) bolus or bivalirudin IV bolus of 0.75mg/kg followed by an infusion of 1.75mg/kg/h until the end of the PCI. The VASP index and thrombin generation test were used to assess the course of platelet reactivity (PR) and thrombin generation. RESULTS: Thrombin generation and PR were identical in both groups at baseline. There was no difference in the course of PR following the LD over time. An optimal PR inhibition was reached 4h after the LD of ticagrelor. Heparin and bivalirudin infusion effectively inhibited thrombin generation during PCI. However, 4h after the end of bivalirudin infusion, thrombin generation had returned to its baseline value whereas in the heparin group it remained significantly inhibited compared to baseline and to the bivalirudin group 4h after the end of the infusion (p<0.01 and p<0.02 respectively). CONCLUSIONS: The present study suggests that the short half-life of bivalirudin and the quick restoration of thrombin activity at a time when optimal PR is not reached may be responsible for acute stent thrombosis. Clinicaltrial.gov: NCT02428725.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Clinical trials have demonstrated an excess of acute stent thrombosis (AST) in acute coronary syndromes patients (ACS) undergoing percutaneous coronary intervention (PCI) with bivalirudin compared to heparin.
Why This Matters for Hirudotherapy
This small prospective randomized study (20 ACS patients undergoing PCI on ticagrelor) compared bivalirudin with heparin to probe why bivalirudin has been linked to excess acute stent thrombosis; the abstract reports that both drugs effectively suppressed thrombin generation during PCI, but four hours after the end of bivalirudin infusion thrombin generation had returned to baseline while it remained significantly inhibited in the heparin group, suggesting bivalirudin's short half-life restores thrombin activity before optimal platelet inhibition is reached. This matters to ASH because bivalirudin is a synthetic analog of hirudin, the prototypical direct thrombin inhibitor isolated from the medicinal leech, so its real-world pharmacodynamics are part of the clinical-evidence story for the leech-derived DTI lineage. Caveat: this is a single, mechanistic randomized trial with only 20 patients examining a surrogate (thrombin generation) rather than clinical outcomes, so the proposed mechanism is preliminary and hypothesis-generating, not a definitive explanation.
Citation
Potential mechanism of acute stent thrombosis with bivalirudin following percutaneous coronary intervention in acute coronary syndromes
Laine M et al. · International journal of cardiology, 2016
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