title: A comparison of bivalirudin to heparin with protamine reversal in patients undergoing cardiac surgery with cardiopulmonary bypass: the EVOLUTION-ON study.
abstract: OBJECTIVE
  Unfractionated heparin and its antidote, protamine sulfate, allow for rapid and reversible anticoagulation during cardiac surgery with cardiopulmonary bypass, yet limitations exist, including a variable dose-response, dependence on a cofactor for anticoagulant effect, and antigenic potential. This trial was performed to evaluate the safety and efficacy of bivalirudin as an alternative to heparin with protamine reversal in on-pump cardiac surgery.
  
  
  METHODS
  We conducted a randomized, open-label, multicenter trial comparing heparin with protamine reversal to bivalirudin in patients undergoing cardiac surgery with cardiopulmonary bypass. The primary objective was to demonstrate comparable rates of in-hospital procedural success defined as freedom from death, Q-wave myocardial infarction, stroke, or repeat revascularization. Twenty-one institutions enrolled 101 patients randomized to bivalirudin and 49 patients to heparin treatment.
  
  
  RESULTS
  The primary end point of procedural success was not significantly different between the bivalirudin arm and the heparin/protamine arms at 7 days, 30 days, or 12 weeks' follow-up. Adequate anticoagulation was achieved in all patients. Secondary end points including mortality, 24-hour blood loss, overall incidence of transfusions, and duration of surgery were similar between the two arms.
  
  
  CONCLUSIONS
  Bivalirudin is a safe and effective anticoagulant for patients undergoing a wide range of cardiac surgical procedures with cardiopulmonary bypass. Procedural success rates with bivalirudin were similar to rates in patients receiving heparin anticoagulation, with no difference in mortality. Avoidance of blood stasis and attention to the intraoperative medical management of patients is critical for successful use of bivalirudin during cardiopulmonary bypass.
authors.affiliation: Carolina Cardiovascular and Thoracic Surgery Associates, Gaston Memorial Hospital, Gastonia, NC 28056, USA. dykec@gmh.org
authors.forename: Cornelius M
authors.initials: CM
authors.lastname: Dyke
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Smedira
authors.forename: Andreas
authors.initials: A
authors.lastname: Koster
authors.forename: Solomon
authors.initials: S
authors.lastname: Aronson
authors.forename: Harry L
authors.initials: HL
authors.lastname: McCarthy
authors.forename: Ronald
authors.initials: R
authors.lastname: Kirshner
authors.forename: A Michael
authors.initials: AM
authors.lastname: Lincoff
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Spiess
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass; D005260:Female; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D006494:Heparin Antagonists / Q000627:therapeutic use*; D006629:Hirudins; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000139:chemically induced / Q000517:prevention & control; D011479:Protamines / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control; D013927:Thrombosis / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D000925:Anticoagulants; D006494:Heparin Antagonists; D006629:Hirudins; D010446:Peptide Fragments; D011479:Protamines; D011994:Recombinant Proteins; D006493:Heparin; C074619:bivalirudin