title: 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.
abstract: 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 (STEMI), 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Boston Scientific and The Medicines Company.
authors.affiliation: New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY 10022, USA. gs2184@columbia.edu
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
authors.forename: Bernhard
authors.initials: B
authors.lastname: Witzenbichler
authors.forename: Giulio
authors.initials: G
authors.lastname: Guagliumi
authors.forename: Jan Z
authors.initials: JZ
authors.lastname: Peruga
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Brodie
authors.forename: Dariusz
authors.initials: D
authors.lastname: Dudek
authors.forename: Ran
authors.initials: R
authors.lastname: Kornowski
authors.forename: Franz
authors.initials: F
authors.lastname: Hartmann
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Gersh
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Pocock
authors.forename: George
authors.initials: G
authors.lastname: Dangas
authors.forename: S Chiu
authors.initials: SC
authors.lastname: Wong
authors.forename: Martin
authors.initials: M
authors.lastname: Fahy
authors.forename: Helen
authors.initials: H
authors.lastname: Parise
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
mesh_terms: D000800:Angioplasty, Balloon / Q000379:methods* / Q000401:mortality; D003131:Combined Modality Therapy; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects; D006629:Hirudins / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009203:Myocardial Infarction / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D017239:Paclitaxel / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D015607:Stents; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D006629:Hirudins; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D006493:Heparin; D017239:Paclitaxel; C074619:bivalirudin