Bivalirudin vs heparin with or without tirofiban during primary percutaneous coronary intervention in acute myocardial infarction: the BRIGHT randomized clinical trial

JAMA. 2015 Apr 7;313(13):1336-46. doi: 10.1001/jama.2015.2323.

Abstract

Importance: The safety and efficacy of bivalirudin compared with heparin with or without glycoprotein IIb/IIIa inhibitors in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are uncertain.

Objective: To determine if bivalirudin is superior to heparin alone and to heparin plus tirofiban during primary PCI.

Design, setting, and participants: Multicenter, open-label trial involving 2194 patients with AMI undergoing primary PCI at 82 centers in China between August 2012 and June 2013.

Interventions: Patients were randomly assigned to receive bivalirudin with a post-PCI infusion (n = 735), heparin alone (n = 729), or heparin plus tirofiban with a post-PCI infusion (n = 730). Among patients treated with bivalirudin, a postprocedure 1.75 mg/kg/h infusion was administered for a median of 180 minutes (IQR, 148-240 minutes).

Main outcomes and measures: The primary end point was 30-day net adverse clinical events, a composite of major adverse cardiac or cerebral events (all-cause death, reinfarction, ischemia-driven target vessel revascularization, or stroke) or bleeding. Additional prespecified safety end points included the rates of acquired thrombocytopenia at 30 days, and stent thrombosis at 30 days and 1 year.

Results: Net adverse clinical events at 30 days occurred in 65 patients (8.8%) of 735 who were treated with bivalirudin compared with 96 patients (13.2%) of 729 treated with heparin (relative risk [RR], 0.67; 95% CI, 0.50-0.90; difference, -4.3%, 95% CI, -7.5% to -1.1%; P = .008); and 124 patients (17.0%) of 730 treated with heparin plus tirofiban (RR for bivalirudin vs heparin plus tirofiban, 0.52; 95% CI, 0.39-0.69; difference, -8.1%, 95% CI, -11.6% to -4.7%; P < .001). The 30-day bleeding rate was 4.1% for bivalirudin, 7.5% for heparin, and 12.3% for heparin plus tirofiban (P < .001). There were no statistically significant differences between treatments in the 30-day rates of major adverse cardiac or cerebral events (5.0% for bivalirudin, 5.8% for heparin, and 4.9% for heparin plus tirofiban, P = .74), stent thrombosis (0.6% vs 0.9% vs 0.7%, respectively, P = .77), acquired thrombocytopenia (0.1% vs 0.7% vs 1.1%; P = .07), or in acute (<24-hour) stent thrombosis (0.3% in each group). At the 1-year follow-up, the results remained similar.

Conclusions and relevance: Among patients with AMI undergoing primary PCI, the use of bivalirudin with a median 3-hour postprocedure PCI-dose infusion resulted in a decrease in net adverse clinical events compared with both heparin alone and heparin plus tirofiban. This finding was primarily due to a reduction in bleeding events with bivalirudin, without significant differences in major adverse cardiac or cerebral events or stent thrombosis.

Trial registration: clinicaltrials.gov Identifier: NCT01696110.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antithrombins / adverse effects
  • Antithrombins / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use*
  • Hemorrhage / chemically induced
  • Heparin / adverse effects
  • Heparin / therapeutic use*
  • Hirudins / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / therapy*
  • Peptide Fragments / adverse effects
  • Peptide Fragments / therapeutic use*
  • Percutaneous Coronary Intervention*
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Tirofiban
  • Tyrosine / adverse effects
  • Tyrosine / analogs & derivatives*
  • Tyrosine / therapeutic use

Substances

  • Antithrombins
  • Fibrinolytic Agents
  • Hirudins
  • Peptide Fragments
  • Recombinant Proteins
  • Tyrosine
  • Heparin
  • Tirofiban
  • bivalirudin

Associated data

  • ClinicalTrials.gov/NCT01696110