Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial

Lancet. 2014 Nov 22;384(9957):1849-1858. doi: 10.1016/S0140-6736(14)60924-7. Epub 2014 Jul 4.

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.

Findings: 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).

Interpretation: 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.

Funding: Liverpool Heart and Chest Hospital, UK National Institute of Health Research, The Medicines Company, AstraZeneca, The Bentley Drivers Club (UK).

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angioplasty, Balloon, Coronary / methods*
  • Angioplasty, Balloon, Coronary / mortality
  • Coronary Angiography / methods
  • Coronary Stenosis / diagnostic imaging*
  • Coronary Stenosis / drug therapy*
  • Coronary Stenosis / mortality
  • Coronary Stenosis / therapy
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Heparin / therapeutic use*
  • Hirudins
  • Humans
  • Infusions, Intravenous
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Peptide Fragments / therapeutic use*
  • Recombinant Proteins / therapeutic use
  • Severity of Illness Index
  • Survival Rate
  • Time Factors
  • Treatment Outcome
  • United Kingdom

Substances

  • Hirudins
  • Peptide Fragments
  • Recombinant Proteins
  • Heparin
  • bivalirudin

Associated data

  • ClinicalTrials.gov/NCT01519518