MDCO-2010 is a novel synthetic agent that actively inhibits plasmin, plasma kallikrein, and coagulation factors Xa and XIa. In 2009, Dietrich et al. reported that the main advantage of this drug, with a similar pharmacologic profile than aprotinin, comes from its potential to inhibit both excessive fibrinolysis and thrombin generation during cardiopulmonary bypass (CPB) (Anesthesiology 2009;110:123-30).
In this article, Englberger et al. report the results of the first study where MDCO-2010 was administered in patients who underwent coronary artery bypass graft surgery with CPB. The primary endpoints were plasma levels and safety parameters, while secondary endpoints were the clinical effects on coagulation, chest tube drainage and transfusion requirements. The authors only evaluated 32 patients: 8 controls and 24 patients randomised to receive different doses of MDCO-2010 (initial loading dosages of 0.005, 0.011, 0.027, 0.047 or 0.094 mg/kg, followed by continuous infusion of 0.0125, 0.025, 0.0625, 0.109, or 0.219 mg/kg/h, respectively). In addition, 0.02, 0.04, 0.09, 0.15, and 0.31 mg were added to the pump prime fluid. The authors found predictable plasma concentrations, with a reduction of blood loss in the three highest dose groups compared to control and a lower incidence of allogeneic blood product transfusions.
Unfortunately, a subsequent multicentre study (ClinicalTrials.gov NCT01530399) was recently stopped in response to unexpected patient safety issues encountered during the trial. Further information is needed before we can judge whether this new molecule could be of potential interest for the reduction of blood loss and transfusion requirements in patients undergoing cardiac surgery with CPB.
– David Faraoni
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