cangrelor and Acute-Disease

Platelet aggregation is the central process in the pathophysiology of acute coronary syndromes. ADP contributes to thrombosis by activating platelets, and AR-C69931MX is a specific antagonist of this process acting at the P2T receptor. At 5 hospitals, 39 patients with unstable angina or non-Q wave myocardial infarction, who were receiving aspirin and heparin, were administered intravenous AR-C69931MX with stepped dose increments over 3 h to a plateau of either 2 microg/kg/min for 21 h (Part 1; n = 12) or up to 69 h (Part 2; n = 13) or 4 microg/kg/min for up to 69 h (Part 3: n = 14). Safety parameters, platelet aggregation (PA) induced by ADP 3 micromol/L (impedance aggregometry), bleeding time (BT) and plasma concentrations of AR-C69931XX were assessed. AR-C69931MX was well tolerated. 33 patients completed the study. There were no deaths at 30 days and no serious adverse events attributed to AR-C69931MX. Trivial bleeding (56%) was common. At 24 h, mean inhibition of PA was 96.0 +/- 8.6, 94.9 +/- 14.4 and 98.7 +/- 2.1% and BT was 9.5 +/- 8.4, 14.0 +/- 9.7 and 16.0 +/- 11.1 min for Parts 1, 2 and 3 respectively. At 1 h post-infusion, mean inhibition of PA was 36.2 +/- 39.2, 20.7 +/- 25.9 and 40.7 +/- 36.7% respectively. 90% patients had a plasma half-life for AR-C69931XX of <9 min. In conclusion, AR-C69931MX is a potent, short-acting platelet ADP receptor antagonist suitable for further studies as an antithrombotic agent.

Topics: Acute Disease; Adenosine Monophosphate; Adult; Aged; Angina, Unstable; Aspirin; Blood Coagulation Tests; Consumer Product Safety; Coronary Disease; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electrocardiography; Female; Heparin; Humans; Male; Membrane Proteins; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2Y12

Optimal anticoagulation strategy for cardiopulmonary bypass (CPB) in end-stage heart failure patients with heparin-induced thrombocytopenia (HIT) requiring left ventricular assist device (LVAD) implantation remains uncertain. Presently, there are no large-scale randomized studies comparing outcomes of alternative anticoagulation strategies for CPB in this patient population. A novel antiplatelet agent - cangrelor, which is a potent P2Y12 inhibitor with robust antiplatelet efficacy, rapid reversibility, and measurable drug effect, has become available since 2015. Intraoperative anticoagulation for CPB using cangrelor with heparin has not been reported before.. We report the case of a 47-year-old male with ischemic cardiomyopathy and acute HIT, who underwent an urgent LVAD implantation using cangrelor with heparin for anticoagulation on CPB. This novel strategy resulted in satisfactory anticoagulation for CPB without perioperative thromboembolic events or major bleeding requiring reoperation.. Cangrelor with heparin was an effective anticoagulation strategy for CPB in this critically ill patient with acute HIT requiring an urgent LVAD implantation. Further studies are warranted to evaluate its efficacy and replicability in other patients with acute or subacute HIT who require urgent cardiac surgery.

Topics: Acute Disease; Adenosine Monophosphate; Anticoagulants; Blood Coagulation Disorders; Cardiopulmonary Bypass; Drug Therapy, Combination; Heart-Assist Devices; Heparin; Humans; Intraoperative Complications; Male; Middle Aged; Platelet Aggregation Inhibitors; Prosthesis Implantation; Thrombocytopenia