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

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 (0·75 mg/kg intravenous bolus followed by 1·75 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 (15·6% vs 18·3%, hazard ratio [HR] 0·83, 95% CI 0·71-0·97, p=0·022), as a result of a lower rate of major bleeding in the bivalirudin group (5·8% vs 9·2%, HR 0·61, 0·48-0·78, p<0·0001). The rate of MACE was similar between groups (11·9% vs 11·9%, HR 1·00, 0·82-1·21, p=0·98). The 1-year rates of cardiac mortality (2·1% vs 3·8%, HR 0·57, 0·38-0·84, p=0·005) and all-cause mortality (3·5% vs 4·8%, HR 0·71, 0·51-0·98, p=0·037) 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.