BivaliRudin with prolonged full-dose Infusion during primary PCI versus Heparin Trial - BRIGHT-4

Nov 06, 2022
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, FACC, MBA
Trial Sponsor:
Chinese Society of Cardiology Foundation; Jiangsu Hengrui Pharmaceuticals
Date Presented:
11/06/2022
Date Published:
11/06/2022
Original Posted Date:
11/06/2022
References

Contribution To Literature:

The BRIGHT-4 trial showed that bivalirudin is superior to UFH monotherapy in reducing bleeding and ischemic events at 30 days among patients with STEMI undergoing primary PCI.

Description:

The goal of the trial was to evaluate the safety and efficacy of a high-dose infusion of bivalirudin after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) compared with unfractionated heparin (UFH).

Study Design

Patients were randomized in an open-label 1:1 fashion to either bivalirudin (n = 3,009) or UFH (n = 3,007). Bivalirudin was given as a bolus of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/hr during the PCI procedure and for 2-4 hours afterwards. An additional bolus of 0.3 mg/kg was given if the activated clotting time measured 5 minutes after the initial bolus, was <225 seconds. The infusion dose was reduced to 1.0 mg/kg/hr in patients with an estimated glomerular filtration rate (eGFR) <30 mL/min, and to 0.25 mg/kg/hr in patients on dialysis. In the heparin group, an initial bolus dose of 70 U/kg was administered. Additional heparin was administered if the 5-minute post-bolus activated clotting time was <225 seconds. Provisional glycoprotein IIb/IIIa inhibition (GPI) with tirofiban was allowed in both groups only for thrombotic complications during the PCI procedure.

  • Total randomized: 6,016
  • Duration of follow-up: 30 days
  • Mean patient age: 60.5 years
  • Percentage female: 22%

Inclusion criteria:

  • STEMI within 48 hours undergoing primary PCI

Exclusion criteria:

  • Thrombolytic therapy
  • Anticoagulant or GPI use within 48 hours prior
  • Mechanical complication of MI

Other salient features/characteristics:

  • Mean body mass index: 25 mg/k2
  • Killip class III/IV: 10.5%
  • Transradial access: 93%
  • Use of ticagrelor: 66%
  • Average duration of bivalirudin infusion post-PCI: 3 hours
  • GPI use for bivalirudin vs. UFH: 11.5% vs. 13.7% (p = 0.01)

Principal Findings:

The primary outcome, all-cause bleeding or BARC 3-5 bleeding at 30 days, for bivalirudin vs. UFH, was: 3.1% vs. 4.4% (hazard ratio 0.69, 95% confidence interval 0.53-0.91, p = 0.007).

Secondary outcomes for bivalirudin vs. UFH:

  • All-cause mortality: 3.0% vs. 3.6% (p = 0.04)
  • BARC 3-5 bleeding: 0.2% vs. 0.8% (p = 0.0014)
  • Reinfarction: 0.6% vs. 0.8% (p = 0.22)
  • Stent thrombosis: 0.4% vs. 1.1% (p = 0.0015)

Interpretation:

The results of this trial show that bivalirudin is superior to UFH monotherapy in reducing bleeding and ischemic events at 30 days among patients with STEMI undergoing primary PCI. A major difference compared with prior trials is the routine continuation of full-dose bivalirudin infusion for 2-4 hours (mean 3 hours) post-PCI. Nearly two-thirds of these patients received ticagrelor and the majority were done via transradial access.

The use of bivalirudin during PCI has been a subject of much debate. While most of the earlier trials compared bivalirudin therapy to UFH + GPI and suggested a benefit primarily in terms of bleeding, the HEAT-PPCI trial suggested that bivalirudin use during primary PCI was not associated with bleeding improvements compared with heparin monotherapy, but had a higher stent thrombosis risk. This was embellished in the results of a large meta-analysis. In contrast, the BRIGHT trial (also performed in China) suggested that bivalirudin monotherapy is superior to UFH among STEMI patients for bleeding, with no difference in stent thrombosis rates. Also, in the MATRIX trial, prolonged bivalirudin infusion post-PCI did not improve outcomes, but a post hoc analysis suggested that full-dose bivalirudin post-PCI had the lowest ischemic risk. The 2017 European Society of Cardiology STEMI guidelines downgraded bivalirudin use for primary PCI to a Class IIa recommendation; in contrast, UFH has a Class I recommendation. It is unclear if the current trial with inherent design limitations (open-label, Chinese patients only) will influence future guidelines; other trials on this topic are also ongoing.

References:

Li Y, Liang Z, Qin L, et al. Bivalirudin plus a high-dose infusion versus heparin monotherapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a randomized trial. Lancet 2022;Nov 6:[Epub ahead of print].

Presented by Dr. Yaling Han at the American Heart Association Resuscitation Science Symposium, Chicago, IL, November 6, 2022.

Clinical Topics: Anticoagulation Management, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Vascular Medicine, Interventions and Vascular Medicine, Chronic Angina

Keywords: AHA Annual Scientific Sessions, AHA22, Anticoagulants, Antithrombins, Glomerular Filtration Rate, Glycoproteins, Hemorrhage, Heparin, Percutaneous Coronary Intervention, Myocardial Infarction, Myocardial Ischemia, ST Elevation Myocardial Infarction, Stents, Thrombosis


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