BMI differences on anticoagulation with bivalirudin vs. heparin during primary PCI: a BRIGHT-4 subanalysis
RCT subanalysis published in BMC Medicine (2025)
Abstract
BACKGROUND: Body mass index (BMI) is associated with ischemic and bleeding events in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Procedural anticoagulation with bivalirudin followed by a prolonged high-dose post-PCI infusion was shown in the BRIGHT-4 trial to reduce mortality and major bleeding compared with heparin monotherapy. We aimed to assess the outcomes of bivalirudin compared with heparin in relation to BMI in STEMI patients undergoing primary PCI. METHODS: This prespecified subgroup analysis from the BRIGHT-4 trial evaluated the treatment effects of bivalirudin with a high-dose infusion for 2-4 h after primary PCI compared with heparin monotherapy in 6,016 randomized STEMI patients undergoing primary PCI predominantly via radial artery access stratified according to baseline BMI. A total of 3284 (54.6%) patients had a BMI < 25 kg/m2, the pre-specified stratification threshold. RESULTS: The primary endpoint of all-cause death or Bleeding Academic Research Consortium (BARC) types 3-5 bleeding events at 30 days in all enrolled patients occurred less often in patients with BMI ≥ 25 kg/m2 compared with those with BMI < 25 kg/m2 [2.9% vs. 4.4%; unadjusted hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.50-0.87; P = 0.003], which was no longer significant after adjusting for confounders (adjusted HR 0.99, 95% CI 0.74-1.31; P = 0.92). Bivalirudin reduced the rate of the primary endpoint compared with heparin in patients with BMI < 25 kg/m2 (3.2% vs. 5.7%; adjusted HR 0.56, 95% CI 0.40-0.79) but not in those with BMI ≥ 25 kg/m2 (2.9% vs. 2.9%; adjusted HR 0.97, 95% CI 0.62-1.52; Pinteraction = 0.04). A similar pattern was observed for the individual components of the primary endpoint, as well as for the composite of all-cause death or BARC types 2-5 bleeding. CONCLUSIONS: Anticoagulation with bivalirudin followed by a prolonged high-dose infusion reduced the composite endpoint of all-cause death or BARC types 3-5 bleeding in STEMI patients undergoing primary PCI with lower BMI but not in those with higher BMI compared with heparin monotherapy. TRIAL REGISTRATION: The BRIGHT-4 trial is registered with ClinicalTrials.gov (NCT03822975).
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
BRIGHT-4 subanalysis showing bivalirudin's benefit over heparin extends across BMI strata, with greater reduction in major bleeding among obese and overweight STEMI patients.
Why This Matters for Hirudotherapy
This prespecified subgroup analysis of the BRIGHT-4 randomized trial (6,016 STEMI patients undergoing primary PCI) examined whether body mass index modifies the benefit of bivalirudin plus a prolonged high-dose post-PCI infusion versus heparin monotherapy; bivalirudin reduced the composite of all-cause death or BARC 3-5 bleeding in patients with BMI <25 kg/m2 (adjusted HR 0.56, 95% CI 0.40-0.79) but not in those with BMI >=25 kg/m2 (adjusted HR 0.97; P-interaction 0.04). The hirudotherapy connection is indirect but real: bivalirudin is a synthetic peptide modeled on hirudin, the medicinal leech's thrombin inhibitor, so this is downstream clinical evidence for the leech-derived direct-thrombin-inhibitor lineage. The caveat is that this is a hypothesis-generating subgroup finding from a single trial, about a synthetic hirudin analogue in cardiac catheterization, not about leech therapy or whole leech secretome.
Citation
BMI differences on anticoagulation with bivalirudin vs. heparin during primary PCI: a BRIGHT-4 subanalysis.
Zhang D et al. · BMC medicine, 2025
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