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).
RCT Entities:
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).
Authors: Matthew E Harinstein; Javed Butler; Stephen J Greene; Gregg C Fonarow; Norman L Stockbridge; Christopher M O'Connor; Marc A Pfeffer; Mandeep R Mehra; Scott D Solomon; Clyde W Yancy; Mona Fiuzat; Robert J Mentz; Sean P Collins; John J V McMurray; Muthiah Vaduganathan; Preston M Dunnmon; Giuseppe M C Rosano; Wilfried Dinh; Frank Misselwitz; Robert O Bonow; Mihai Gheorghiade Journal: Heart Fail Rev Date: 2015-07 Impact factor: 4.214
Authors: Neal W Dickert; David Wendler; Chandan M Devireddy; Sara F Goldkind; Yi-An Ko; Candace D Speight; Scott Yh Kim Journal: Clin Trials Date: 2018-10-03 Impact factor: 2.486