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Randomized Controlled Trial
. 2024 Sep 27;22(1):410.
doi: 10.1186/s12916-024-03579-6.

Bivalirudin versus heparin in patients with or without bail-out GPI use: a pre-specified subgroup analysis from the BRIGHT-4 trial

Jia Liao  1   2 , Miaohan Qiu  1 , Xiaojian Feng  3 , Kui Chen  4 , Dingbao Zhang  5 , Yuncheng Zou  6 , Xiaohui Zheng  7 , Gang Zhao  8 , Nailiang Tian  9 , Zeqi Zheng  10 , Xiaoping Peng  10 , Qing Yang  11 , Zhenyang Liang  1 , Yi Li  12 , Yaling Han  13 , Gregg W Stone  14
Affiliations
Randomized Controlled Trial

Bivalirudin versus heparin in patients with or without bail-out GPI use: a pre-specified subgroup analysis from the BRIGHT-4 trial

Jia Liao et al. BMC Med. .

Abstract

Background: Conflicting results comparing bivalirudin versus heparin anticoagulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), in part due to the confounding effect of glycoprotein IIb/IIIa inhibitors (GPI). The aim of the study was to compare the safety and effectiveness of bivalirudin plus a post-PCI high-dose infusion vs heparin with or without bail-out GPI use.

Methods: We conducted a pre-specified subgroup analysis from the BRIGHT-4 trial that randomized 6016 STEMI patients who underwent primary PCI to receive either bivalirudin plus a post-PCI high-dose infusion for 2-4 h or heparin monotherapy. GPI use was only reserved as bail-out therapy for procedural thrombotic complications. The primary outcome was a composite of all-cause death or Bleeding Academic Research Consortium (BARC) types 3-5 bleeding at 30 days.

Results: A total of 5250 (87.4%) patients received treatment without GPI while 758 (12.6%) received bail-out GPI. Bail-out GPI use was associated with an increased risk of the primary outcome compared to non-GPI use (5.28% vs. 3.41%; adjusted hazard ratio (aHR), 1.62; 95% confidence interval (CI), 1.13-2.33; P = 0.009) and all-cause death (5.01% vs. 3.12%; aHR, 1.74; 95% CI, 1.20-2.52; P = 0.004) but not in the risk of BARC types 3-5 bleeding (0.53% vs. 0.48%; aHR, 0.90; 95% CI, 0.31-2.66; P = 0.85). Among patients without GPI use, bivalirudin was associated with lower rates of the primary outcome (2.63% vs. 4.21%; aHR, 0.55; 95% CI, 0.39-0.77; P = 0.0005), all-cause death (2.52% vs. 3.74%; aHR, 0.58; 95% CI, 0.41-0.83; P = 0.003), and BARC types 3-5 bleeding (0.15% vs. 0.81%; aHR, 0.19; 95% CI, 0.06-0.57; P = 0.003) compared with heparin. However, among patients requiring bail-out GPI, there were no significant differences observed in the rates of the primary outcome (5.76% vs. 4.87%; aHR, 0.77; 95% CI, 0.36-1.66; P = 0.50; Pinteraction = 0.07) or its individual components between bivalirudin and heparin groups.

Conclusions: Bivalirudin plus a post-PCI high-dose infusion was associated with significantly reduced 30-day composite rate of all-cause death or BARC types 3-5 bleeding compared with heparin monotherapy in STEMI patients undergoing primary PCI without GPI use. However, these benefits might be less pronounced in patients requiring bail-out GPI due to thrombotic complications during primary PCI.

Trial registration: ClinicalTrials.gov NCT03822975.

Keywords: BRIGHT-4; Bivalirudin plus high-dose infusion; Glycoprotein IIb/IIIa inhibitors; Heparin; Procedural thrombotic complications.

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Conflict of interest statement

Dr. Stone has received speaker honoraria from Medtronic, Pulnovo, Abiomed, Amgen, Boehringer Ingelheim; has served as a consultant to Abbott, Daiichi Sankyo, Ablative Solutions, CorFlow, Cardiomech, Robocath, Miracor, Vectorious, Apollo Therapeutics, Elucid Bio, Cardiac Success, Valfix, TherOx, HeartFlow, Neovasc, Ancora, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, Oxitope, HighLife, Elixir, Remote Cardiac Enablement, Aria; and has equity/options from Cardiac Success, Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Valfix, Xenter. Dr. Stone’s employer, Mount Sinai Hospital, receives research grants from Shockwave, Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Vascular Dynamics, Pulnovo, V-wave and PCORI (via Weill Cornell Medical Center). The other authors declare that they have no potential competing interests.

Figures

Fig. 1
Fig. 1
Kaplan–Meier curves for the 30-day primary endpoint of all-cause death or BARC types 3–5 bleeding. Cumulative incidences during follow-up in patients treated with bivalirudin plus a post-PCI high-dose infusion vs heparin, each with or without bail-out GPI use, for (A) the primary outcome (the composite of all-cause death or BARC types 3–5 bleeding); B all-cause death; and (C) BARC types 3–5 bleeding. * Unadjusted HR for bivalirudin without GPI versus heparin without GPI. ** Unadjusted HR for bivalirudin with GPI versus heparin with GPI. BARC, Bleeding Academic Research Consortium; GPI, glycoprotein IIb/IIIa inhibitors; HR, hazard ratio; CI, confidence interval
Central illustration.
Central illustration.
Thirty-day outcomes of bivalirudin plus a post-PCI high-dose infusion for 2-4 hours compared with heparin in patients with and without bail-out GPI use. The primary outcome was a composite of all-cause death or BARC types 3-5 bleeding at 30 days. *All HR (95% CI) were adjusted for potential confounding factors, except for BARC types 3-5 bleeding in patients with bail-out GPI use, which could not be adjusted due to the low number of events. BARC, Bleeding Academic Research Consortium; GPI, glycoprotein IIb/IIIa inhibitors; CI, confidence interval.
See this image and copyright information in PMC

References

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