Efficacy and safety of heparinase I versus protamine in patients undergoing coronary artery bypass grafting withl and without cardiopulmonary bypass

Background: Hemodynamic protamine reactions with heparin reversal during cardiac surgery are common and associated with adverse outcomes. As an alternative to protamine, the authors examined heparinase I reversal of heparin after aorto-coronary bypass graft surgery. Methods: In a randomized, double-blind, double-dummy trial, 167 on- and off-pump aorto-coronary bypass graft surgery patients received either heparinase I (maximum 35 mu g/kg) or protamine (maximum 650 mg) for heparin reversal, monitored by activated clotting time values and clinical assessment. Hemodynamic parameters were recorded electronically; safety evaluation was to 30 days postoperatively. Noninferiority was pre-defined as 400 ml or less median 12-h chest tube drainage from intensive care unit arrival for heparinase I patients, after risk adjustment. Hemodynamic instability was defined as systemic hypotension (>= 30 mmHg decrease) and/or pulmonary hypertension (>= 40 mmHg with an increase 2 10mmHg) within 30 min of heparin reversal initiation. Results: Patient enrollment was terminated on advisement of the Data Safety Monitoring Board. Although heparinase I was noninferior for 12-h chest tube drainage, protamine had a superior safety profile. Overall, heparinase I subjects had longer hospital stays (P = 0.04), were more likely to experience a serious adverse event (P = 0.01), and were less likely to avoid transfusion (P = 0.006). A composite morbidity score was not different (P = 0.24), and similar rates of hemodynamic instability were observed between groups. Findings were consistent in analyses stratified by on- and off-pump surgery. Conclusions: Heparinase I reverses heparin anticoagulation after aortocoronary bypass graft surgery but is not equivalent to protamine because of its inferior safety profile.