Greenbaum Adam B, Ohman E Magnus, Gibson C Michael, Borzak Steven, Stebbins Amanda L, Lu Mei, Le May Michel R, Stankowski Jill E, Emanuelsson Hakan, Weaver W Douglas
Henry Ford Heart and Vascular Institute, Detroit, MI, USA.
Am Heart J. 2007 Oct;154(4):702-9. doi: 10.1016/j.ahj.2007.06.001.
Fibrinolytic therapy for acute myocardial infarction (AMI) results in normal flow in only about half of patients. Adjunctive treatment with potent antiplatelet and antithrombin agents increases arterial patency but is associated with excessive bleeding. Cangrelor (formerly AR-C69931MX) is a rapidly acting, specific antagonist of platelet aggregation via binding to the adenosine diphosphate P2Y12 receptor subtype. The aim of this study was to assess the safety and coronary artery patency of cangrelor as an adjunct to alteplase (tissue plasminogen activator [t-PA]).
Patients with AMI received aspirin, heparin, and an intravenous infusion of either cangrelor alone, full-dose t-PA alone, or 1 of 3 doses of cangrelor along with half-dose t-PA. The primary end point was Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow at 60 minutes. Secondary end points included TIMI frame count, TIMI myocardial perfusion grade, extent of ST-segment resolution, composite clinical events, and bleeding.
Ninety-two of planned 180 patients were enrolled. The combination of cangrelor and half-dose t-PA resulted in similar 60-minute patency as full-dose t-PA alone (55% vs 50%, P = not significant) and greater patency than with cangrelor alone (55% vs 18%, P < .05). The percentage of patients achieving >70% ST-segment resolution at 60 minutes tended to be greater with combination therapy than with either cangrelor or t-PA alone (28% vs 13%, P = .13 and 28% vs 14%, P = .30, respectively). Bleeding and adverse clinical events were comparable among the groups.
This first experience with the intravenous P2Y12 receptor inhibitor, cangrelor, suggests the potential of this compound as an adjunct to fibrinolysis during treatment of AMI.
急性心肌梗死（AMI）的纤溶治疗仅使约一半患者的血流恢复正常。联合使用强效抗血小板和抗凝血酶药物可提高动脉通畅率，但会增加出血风险。坎格雷洛（原AR-C69931MX）是一种通过与二磷酸腺苷P2Y12受体亚型结合而快速起效的特异性血小板聚集拮抗剂。本研究旨在评估坎格雷洛作为阿替普酶（组织纤溶酶原激活剂[t-PA]）辅助药物的安全性和冠状动脉通畅情况。
AMI患者接受阿司匹林、肝素治疗，并静脉输注单独的坎格雷洛、单独的全剂量t-PA或三种剂量的坎格雷洛之一与半剂量t-PA。主要终点是60分钟时心肌梗死溶栓（TIMI）3级血流。次要终点包括TIMI帧计数、TIMI心肌灌注分级、ST段分辨率程度、综合临床事件和出血情况。
计划纳入的180例患者中有92例入组。坎格雷洛与半剂量t-PA联合使用导致60分钟时的通畅率与单独使用全剂量t-PA相似（55%对50%，P无统计学意义），且通畅率高于单独使用坎格雷洛（55%对18%，P<.05）。联合治疗组在60分钟时ST段分辨率>70%的患者百分比倾向于高于单独使用坎格雷洛或t-PA组（分别为28%对13%，P=.13；28%对14%，P=.30）。各组之间的出血和不良临床事件相当。
静脉注射P2Y12受体抑制剂坎格雷洛的首次经验表明，该化合物在AMI治疗期间作为纤溶辅助药物具有潜力。
