A comparison of bivalirudin to heparin with protamine reversal in patients undergoing cardiac surgery with cardiopulmonary bypass: the EVOLUTION-ON study.
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.
Dyke
Cornelius M
CM
Carolina Cardiovascular and Thoracic Surgery Associates, Gaston Memorial Hospital, Gastonia, NC 28056, USA. dykec@gmh.org
Smedira
Nicholas G
NG
Koster
Andreas
A
Aronson
Solomon
S
McCarthy
Harry L
HL
Kirshner
Ronald
R
Lincoff
A Michael
AM
Spiess
Bruce D
BD
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
D000925:Anticoagulants; D006494:Heparin Antagonists; D006629:Hirudins; D010446:Peptide Fragments; D011479:Protamines; D011994:Recombinant Proteins; D006493:Heparin; C074619:bivalirudin