title: Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial.
abstract: BACKGROUND
  Bivalirudin, with selective use of glycoprotein (GP) IIb/IIIa inhibitor agents, is an accepted standard of care in primary percutaneous coronary intervention (PPCI). We aimed to compare antithrombotic therapy with bivalirudin or unfractionated heparin during this procedure.
  
  
  METHODS
  In our open-label, randomised controlled trial, we enrolled consecutive adults scheduled for angiography in the context of a PPCI presentation at Liverpool Heart and Chest Hospital (Liverpool, UK) with a strategy of delayed consent. Before angiography, we randomly allocated patients (1:1; stratified by age [<75 years vs ≥75 years] and presence of cardiogenic shock [yes vs no]) to heparin (70 U/kg) or bivalirudin (bolus 0·75 mg/kg; infusion 1·75 mg/kg per h). Patients were followed up for 28 days. The primary efficacy outcome was a composite of all-cause mortality, cerebrovascular accident, reinfarction, or unplanned target lesion revascularisation. The primary safety outcome was incidence of major bleeding (type 3-5 as per Bleeding Academic Research Consortium definitions). This study is registered with ClinicalTrials.gov, number NCT01519518.
  
  
  RESULTS
  Between Feb 7, 2012, and Nov 20, 2013, 1829 of 1917 patients undergoing emergency angiography at our centre (representing 97% of trial-naive presentations) were randomly allocated treatment, with 1812 included in the final analyses. 751 (83%) of 905 patients in the bivalirudin group and 740 (82%) of 907 patients in the heparin group had a percutaneous coronary intervention. The rate of GP IIb/IIIa inhibitor use was much the same between groups (122 patients [13%] in the bivalirudin group and 140 patients [15%] in the heparin group). The primary efficacy outcome occurred in 79 (8·7%) of 905 patients in the bivalirudin group and 52 (5·7%) of 907 patients in the heparin group (absolute risk difference 3·0%; relative risk [RR] 1·52, 95% CI 1·09-2·13, p=0·01). The primary safety outcome occurred in 32 (3·5%) of 905 patients in the bivalirudin group and 28 (3·1%) of 907 patients in the heparin group (0·4%; 1·15, 0·70-1·89, p=0·59).
  
  
  CONCLUSIONS
  Compared with bivalirudin, heparin reduces the incidence of major adverse ischaemic events in the setting of PPCI, with no increase in bleeding complications. Systematic use of heparin rather than bivalirudin would reduce drug costs substantially.
  
  
  BACKGROUND
  Liverpool Heart and Chest Hospital, UK National Institute of Health Research, The Medicines Company, AstraZeneca, The Bentley Drivers Club (UK).
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: Adeel
authors.initials: A
authors.lastname: Shahzad
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Kemp
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: Christine
authors.initials: C
authors.lastname: Mars
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: Keith
authors.initials: K
authors.lastname: Wilson
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Roome
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: Rob
authors.initials: R
authors.lastname: Cooper
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Andron
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: Clare
authors.initials: C
authors.lastname: Appleby
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Fisher
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: Aleem
authors.initials: A
authors.lastname: Khand
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: Babu
authors.initials: B
authors.lastname: Kunadian
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Mills
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: John L
authors.initials: JL
authors.lastname: Morris
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: William L
authors.initials: WL
authors.lastname: Morrison
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: Shahzad
authors.initials: S
authors.lastname: Munir
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: Nick D
authors.initials: ND
authors.lastname: Palmer
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: Raphael A
authors.initials: RA
authors.lastname: Perry
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Ramsdale
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
authors.forename: Periaswamy
authors.initials: P
authors.lastname: Velavan
authors.affiliation: Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK. Electronic address: rod.stables@lhch.nhs.uk.
authors.forename: Rod H
authors.initials: RH
authors.lastname: Stables
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary / Q000379:methods* / Q000401:mortality; D017023:Coronary Angiography / Q000379:methods; D023921:Coronary Stenosis / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006493:Heparin / Q000627:therapeutic use*; D006629:Hirudins; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012720:Severity of Illness Index; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D006493:Heparin; C074619:bivalirudin