McKellar Stephen H, Thompson Jess L, Garcia-Rinaldi Raul F, Macdonald Ryan J, Sundt Thoralf M, Schaff Hartzell V
Division of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota 55905, USA.
J Thorac Cardiovasc Surg. 2008 Oct;136(4):908-14. doi: 10.1016/j.jtcvs.2008.01.045. Epub 2008 Jun 30.
In the interest of exploring alternatives to warfarin, we tested the hypothesis that clopidogrel combined with aspirin is effective for thromboprophylaxis of mechanical valves using a swine model.
Adult swine underwent heterotopic implantation of a modified bileaflet mechanical valved conduit bypassing the ligated, native descending thoracic aorta. Animals were randomized to no anticoagulation (n = 7), 175 U/kg dalteparin administered subcutaneously twice daily (n = 9), 325 mg of aspirin (n = 6), 75 mg of clopidogrel (n = 6), or 325 mg of aspirin and 75 mg of clopidogrel daily (n = 6) and survived for 30 days. Additionally, 11 animals were randomized to no anticoagulation (n = 5) or 325 mg of oral aspirin and 75 mg of clopidogrel daily (n = 6) and survived for 150 days.
At 30 days, we observed 216 +/- 270 mg of thrombus for the no anticoagulation group, 53 +/- 91 mg for the dalteparin group, 33 +/- 23 mg for the aspirin group, 25 +/- 10 mg for the clopidogrel group, and 17 +/- 9 mg for the combined aspirin and clopidogrel group, respectively (P < .01 for clopidogrel and aspirin vs no anticoagulation). At 150 days, we observed 223 +/- 200 mg of thrombus for the no anticoagulation group and 4 +/- 4 mg for the aspirin and clopidogrel group (P = .02). Mean platelet deposition on the valve was 4.1 x 10(9) +/- 3.6 x 10(9) for the no anticoagulation and 6.81 x 10(7) +/- 1.4 x 10(8) for the combined aspirin and clopidogrel groups, respectively (P = .03). No major hemorrhagic events were observed.
Effective short- and long-term thromboprophylaxis of mechanical valves can be achieved by using dual-antiplatelet therapy in this porcine model. Prospective human trials should be conducted with combination aspirin and clopidogrel as an alternative to warfarin in patients with bileaflet mechanical aortic valves.
为了探索华法林的替代药物，我们采用猪模型检验了氯吡格雷联合阿司匹林对机械瓣膜进行血栓预防有效的假设。
成年猪接受改良双叶机械瓣膜导管的异位植入，绕过结扎的天然降胸主动脉。动物被随机分为不进行抗凝治疗组（n = 7）、每天两次皮下注射175 U/kg达肝素组（n = 9）、325 mg阿司匹林组（n = 6）、75 mg氯吡格雷组（n = 6）或每天325 mg阿司匹林加75 mg氯吡格雷组（n = 6），并存活30天。此外，11只动物被随机分为不进行抗凝治疗组（n = 5）或每天口服325 mg阿司匹林加75 mg氯吡格雷组（n = 6），并存活150天。
在30天时，我们观察到不进行抗凝治疗组的血栓为216±270 mg，达肝素组为53±91 mg，阿司匹林组为33±23 mg，氯吡格雷组为25±10 mg，阿司匹林与氯吡格雷联合组为17±9 mg（氯吡格雷和阿司匹林联合组与不进行抗凝治疗组相比，P <.01）。在150天时，我们观察到不进行抗凝治疗组的血栓为223±200 mg，阿司匹林与氯吡格雷联合组为4±4 mg（P =.02）。不进行抗凝治疗组瓣膜上的平均血小板沉积为4.1×10⁹±3.6×10⁹，阿司匹林与氯吡格雷联合组为6.81×10⁷±1.4×10⁸（P =.03）。未观察到重大出血事件。
在该猪模型中，使用双联抗血小板治疗可实现机械瓣膜有效的短期和长期血栓预防。对于双叶机械主动脉瓣患者，应进行阿司匹林和氯吡格雷联合用药作为华法林替代药物的前瞻性人体试验。
