Heparin plus a glycoprotein IIb/IIIa inhibitor versus bivalirudin monotherapy and paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction (HORIZONS-AMI): final 3-year results from a multicentre, randomised controlled trial

Background Primary results of the HORIZONS-AMI trial have been previously reported. In this final report, we aimed to assess 3-year outcomes. Methods HORIZONS-AMI was a prospective, open-label, randomised trial undertaken at 123 institutions in 11 countries. Patients aged 18 years or older were eligible for enrolment if they had ST-segment elevation myocardial infarction (STEM!), presented within 12 h after onset of symptoms, and were undergoing primary percutaneous coronary intervention. By use of a computerised interactive voice response system, we randomly allocated patients 1:1 to receive bivalirudin or heparin plus a glycoprotein IIb/IIIa inhibitor (GPI; pharmacological randomisation; stratified by previous and expected drug use and study site) and, if eligible, randomly allocated 3:1 to receive a paclitaxel-eluting stent or a bare metal stent (stent randomisation; stratified by pharmacological group assignment, diabetes mellitus status, lesion length, and study site). We produced Kaplan-Meier estimates of major adverse cardiovascular events at 3 years by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00433966. Findings Compared with 1802 patients allocated to receive heparin plus a GPI, 1800 patients allocated to bivalirudin monotherapy had lower rates of all-cause mortality (5.9% vs 7.7%, difference -1.9% [-3.5 to 0.2], HR 0.75 [0.58-0.97]; p=0.03), cardiac mortality (2.9% vs 5.1%, -2.2% [-3.5 to -0.9], 0.56 [0.40-0.80]; p=0.001), reinfarction (6.2% vs 8.2%, 1.9% [-3.7 to -0.2], 0.76 [0.59-0.99]; p=0.04), and major bleeding not related to bypass graft surgery (6.9% vs 10.5%, -3.6% [-5.5 to -1.7], 0.64 [0.51-0.80]; p=0.0001) at 3 years, with no significant differences in ischaemia-driven target vessel revascularisation, stent thrombosis, or composite adverse events. Compared with 749 patients who received a bare-metal stent, 2257 patients who received a paclitaxel-eluting stent had lower rates of ischaemia-driven target lesion revascularisation (9.4% vs 15.1%, -5.7% [-8.6 to -2.7], 0.60 [0.48-0.76]; p<0.0001) after 3 years, with no significant differences in the rates of death, reinfarction, stroke or stent thrombosis. Stent thrombosis was high (>= 4.5%) in both groups. Interpretation The effectiveness and safety of bivalirudin monotherapy and paclitaxel-eluting stenting are sustained at 3 years for patients with STEMI undergoing primary percutaneous coronary intervention.