Bivalirudin in patients undergoing primary angioplasty for acute myocardial infarction (HORIZONS-AMI): 1-year results of a randomised controlled trial

R Mehran, AJ Lansky, B Witzenbichler, G Guagliumi… - The Lancet, 2009 - thelancet.com
R Mehran, AJ Lansky, B Witzenbichler, G Guagliumi, JZ Peruga, BR Brodie, D Dudek…
The Lancet, 2009thelancet.com
Summary Background In the HORIZONS-AMI trial, patients with acute ST-segment elevation
myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) who
were treated with the thrombin inhibitor bivalirudin had substantially lower 30-day rates of
major haemorrhagic complications and net adverse clinical events than did patients
assigned to heparin plus a glycoprotein IIb/IIIa inhibitor (GPI). Here, we assess whether
these initial benefits were maintained at 1 year of follow-up. Methods Patients aged 18 years …
Background
In the HORIZONS-AMI trial, patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) who were treated with the thrombin inhibitor bivalirudin had substantially lower 30-day rates of major haemorrhagic complications and net adverse clinical events than did patients assigned to heparin plus a glycoprotein IIb/IIIa inhibitor (GPI). Here, we assess whether these initial benefits were maintained at 1 year of follow-up.
Methods
Patients aged 18 years or older were eligible for enrolment in this multicentre, open-label, randomised controlled trial if they had STEMI, presented within 12 h after the onset of symptoms, and were undergoing primary PCI. 3602 eligible patients were randomly assigned by interactive voice response system in a 1:1 ratio to receive bivalirudin (0ˇ75 mg/kg intravenous bolus followed by 1ˇ75 mg/kg per h infusion; n=1800) or heparin plus a GPI (control; 60 IU/kg intravenous bolus followed by boluses with target activated clotting time 200–250 s; n=1802). The two primary trial endpoints were major bleeding and net adverse clinical events (NACE; consisting of major bleeding or composite major adverse cardiovascular events [MACE; death, reinfarction, target vessel revascularisation for ischaemia, or stroke]). This prespecified analysis reports data for the 1-year follow-up. Analysis was by intention to treat. Patients with missing data were censored at the time of withdrawal from the study or at last follow-up. This trial is registered with ClinicalTrials.gov, number NCT00433966.
Findings
1-year data were available for 1696 patients in the bivalirudin group and 1702 patients in the control group. Reasons for participant dropout were loss to follow-up and withdrawal of consent. The rate of NACE was lower in the bivalirudin group than in the control group (15ˇ6% vs 18ˇ3%, hazard ratio [HR] 0ˇ83, 95% CI 0ˇ71–0ˇ97, p=0ˇ022), as a result of a lower rate of major bleeding in the bivalirudin group (5ˇ8% vs 9ˇ2%, HR 0ˇ61, 0ˇ48–0ˇ78, p<0ˇ0001). The rate of MACE was similar between groups (11ˇ9% vs 11ˇ9%, HR 1ˇ00, 0ˇ82–1ˇ21, p=0ˇ98). The 1-year rates of cardiac mortality (2ˇ1% vs 3ˇ8%, HR 0ˇ57, 0ˇ38–0ˇ84, p=0ˇ005) and all-cause mortality (3ˇ5% vs 4ˇ8%, HR 0ˇ71, 0ˇ51–0ˇ98, p=0ˇ037) were lower in the bivalirudin group than in the control group.
Interpretation
In patients with STEMI undergoing primary PCI, anticoagulation with bivalirudin reduced the rates of net adverse clinical events and major bleeding at 1 year compared with treatment with heparin plus a GPI. This finding has important clinical implications for the selection of optimum treatment strategies for patients with STEMI.
Funding
Cardiovascular Research Foundation, with unrestricted grant support from Boston Scientific Corporation and The Medicines Company.
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