Hirulog and Early Reperfusion or Occlusion Trial - HERO-2

Description:

A randomized, open-label trial comparing bivalirudin (a thrombin-specific anticoagulant) with heparin in patients undergoing fibrinolysis with streptokinase for acute MI.

Hypothesis:

Patients receiving hirulog would have a 15% mortality reduction relative to heparin at 30 days.

Study Design

Study Design:

Patients Enrolled: 17073
Mean Follow Up: 30 days
Mean Patient Age: any age
Female: 28

Patient Populations:

Presentation within 6 hours of the onset of chest discomfort lasting more than 30 min; At least 1 mm of ST elevation in 2 or more contiguous leads (or at least 2 mm of ST elevation in 2 contiguous precordial leads in V1-V3) or presumed new left bundle branch block.

Exclusions:

active bleeding or known hemorrhagic diathesis; previous stroke; transient ischaemic attack within 6 months; current warfarin therapy; major surgery or trauma within 6 weeks; recent non-compressible vascular puncture; blood pressure of more than 180/110 mm Hg; low-molecular-weight heparin therapy within 12 h; an APTT of at least 50 s in patients who had previously received heparin; and previous treatment with streptokinase.

Primary Endpoints:

30 day mortality

Secondary Endpoints:

reinfarction within 96 hours; in-hospital reinfarction; composite of death within 30 days or in-hospital reinfarction; death or disabling stroke; death within 24 hours; non-fatal reinfarction in hospital; stroke; intracerebral bleeding; bleeding events

Drug/Procedures Used:

All patients received 150-325 mg aspirin. Patients were randomized to either iv bivalirudin for 48 hours (0.25 mg/kg bolus, 0.5 mg/kg infusion for 12 hrs, 0.25 mg/kg for 36 hrs) or open-label unfractionated heparin for 48 hrs (5000 U bolus, infusion of 1000 U/h for pts >=80 kg or 800 U/h for pts <80kg). Streptokinase iv (1.5 million U over 30-60 min) after bivalirudin or UFH bolus.

Principal Findings:

The 30 day mortality rates were 10.8% with bivalirudin vs 10.9% with heparin, (O.R. 0.99, 95% CI 0.90-1.09, p=0.85). Bivalirudin was associated with a lower rate of adjudicated reinfarction within 96 hours than heparin (1.6% vs 2.3%, O.R. 0.70, 95% CI 0.56-0.87, p=0.001). The combined rate of death or adjudicated reinfarction was lower in the bivalirudin group than in the heparin group (adjusted rates 12.6% vs 13.6%, O.R. 0.92 95% C.I. 0.83-1.01, p=0.07). Severe bleeding occurred in 0.7% in the bivalirudin group vs 0.5% in the heparin group (p=0.07), and intracerebral bleeding occurred in 0.6% vs 0.4%, respectively (p=0.09). Moderate and mild bleeding were also significantly higher in the bivalirudin group than the heparin group.

Interpretation:

Bivalirudin, a thrombin-specific anticoagulant, did not significantly reduce mortality at 30 days compared with unfractionated heparin when used in conjunction with streptokinase. However, bivalirudin reduced the rate of adjudicated reinfarction and the combined endpoint of death or reinfarction. Despite these benefits, mild and moderate bleeding was increased in patients receiving bivalirudin. Bivalirudin is a new anticoagulant treatment option in patients with acute myocardial infarction treated with streptokinase.

References:

Lancet 2001;358:1855-1863. (main results) Am J Cardiol 1998 Oct 22;82(8B):57P-62P. (trial design)

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, EP Basic Science

Keywords: Hirudin Therapy, Myocardial Infarction, Streptokinase, Fibrinolysis, Heparin, Recombinant Proteins, Peptide Fragments, Bundle-Branch Block, Hirudins


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