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.

Use of localised intracoronary beta radiation in treatment of in-stent restenosis: the INHIBIT randomised controlled trial.

BACKGROUND: In-stent restenosis is a major limitation of intracoronary stenting. Ionising gamma radiation has been shown to reduce recurrence of restenosis after stent placement. We aimed to compare the effects of intracoronary beta radiation treatment with those of placebo for clinical and angiographic outcomes of patients with diffuse in-stent restenosis. METHODS: 332 patients with in-stent restenosis underwent successful coronary intervention, and were then randomly allocated to intracoronary beta radiation with a phosphorus-32 source (n=166) or placebo (166) delivered into a centreing balloon catheter through an automatic afterloader. Longer lesions (>22 mm of dilated length) were treated with tandem positioning of the study wire. The primary safety endpoint was major adverse cardiac events, defined as death, myocardial infarction, and repeat target-lesion revascularisation at 9 months. The primary efficacy endpoint was binary angiographic restenosis rate in the analysis segment during 9-months' follow-up. Analysis was by intention to treat. FINDINGS: Procedural success, and in-hospital and 30-day complications were similar among the two groups. 24 (15%) patients in the radiated group had the primary safety endpoint of death, myocardial infarction, or repeat target-lesion revascularisation over 290 days compared with 51 [corrected] (31%) in the placebo group (difference 16% [95% CI 7-25], p = 0.0006). Binary angiographic restenosis rate was lower in the radiated group than the placebo group for the entire analysed segment (difference 25% [14--37], p < 0.0001). INTERPRETATION: Vascular brachytherapy using pure beta-emitter 32P delivered into a centreing catheter via an automatic afterloader can be used to reduce overall revascularisation in patients undergoing treatment for diffuse in-stent restenosis.