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

Lancet. 2011 Jun 25;377(9784):2193-204. doi: 10.1016/S0140-6736(11)60764-2. Epub 2011 Jun 12.

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.

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.

Funding: Boston Scientific and The Medicines Company.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angioplasty, Balloon / methods*
  • Angioplasty, Balloon / mortality
  • Combined Modality Therapy
  • Confidence Intervals
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Drug-Eluting Stents
  • Electrocardiography
  • Female
  • Follow-Up Studies
  • Heparin / administration & dosage*
  • Heparin / adverse effects
  • Hirudins / administration & dosage*
  • Hirudins / adverse effects
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / mortality
  • Myocardial Infarction / therapy*
  • Paclitaxel / pharmacology*
  • Peptide Fragments / administration & dosage*
  • Peptide Fragments / adverse effects
  • Platelet Glycoprotein GPIIb-IIIa Complex / administration & dosage
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Prospective Studies
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Stents
  • Survival Analysis
  • Time Factors
  • Treatment Outcome

Substances

  • Hirudins
  • Peptide Fragments
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Recombinant Proteins
  • Heparin
  • Paclitaxel
  • bivalirudin

Associated data

  • ClinicalTrials.gov/NCT00433966