Kamath Sridhar, Blann Andrew D, Chin Bernard S P, Lip Gregory Y H
Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, United Kingdom.
J Am Coll Cardiol. 2002 Aug 7;40(3):484-90. doi: 10.1016/s0735-1097(02)01984-8.
This study was designed to investigate whether or not combination aspirin-clopidogrel therapy would reduce markers of thrombogenesis and platelet activation in atrial fibrillation (AF), in a manner similar to warfarin.
Dose-adjusted warfarin is beneficial as thromboprophylaxis in AF, but potentially serious side effects and regular monitoring leave room for alternative therapies. METHODS; We randomized 70 patients with nonvalvular AF who were not on any antithrombotic therapy to either dose-adjusted warfarin (international normalized ratio 2 to 3) (Group I) or combination therapy with aspirin 75 mg and clopidogrel 75 mg (Group II). Plasma indices of thrombogenesis (fibrin D-dimer, prothrombin fragment 1+2) and platelet activation (beta-thromboglobulin [TG] and soluble P-selectin) were quantified, along with platelet aggregation responses to standard agonists, at baseline (pretreatment) and at six weeks posttreatment. RESULTS; Pretreatment levels of fibrin D-dimer (p = 0.001), beta-TG (p = 0.01) and soluble P-selectin (p = 0.03) were raised in patients with AF, whereas plasma prothrombin fragment 1+2 levels and platelet aggregation were not significantly different compared with controls. Dose-adjusted warfarin reduced plasma levels of fibrin D-dimer, prothrombin fragment 1+2 and beta-thromboglobulin levels at six weeks (all p < 0.001), enhanced plasma levels of soluble P-selectin (p < 0.001) and had no significant effect on platelet aggregation. Aspirin-clopidogrel combination therapy made no difference to the plasma markers of thrombogenesis or platelet activation (all p = NS), but the platelet aggregation responses to adenosine diphosphate (p < 0.001) and epinephrine (p = 0.02) were decreased.
Aspirin-clopidogrel combination therapy failed to reduce plasma indices of thrombogenesis and platelet activation in AF, although some aspects of ex vivo platelet aggregation were altered. Anticoagulation with warfarin may be superior to combination aspirin-clopidogrel therapy as thromboprophylaxis in AF.
本研究旨在调查阿司匹林 - 氯吡格雷联合治疗是否会以类似于华法林的方式降低房颤（AF）患者的血栓形成和血小板活化标志物。
剂量调整后的华法林对房颤患者的血栓预防有益，但潜在的严重副作用和定期监测为替代疗法留下了空间。方法：我们将70例未接受任何抗血栓治疗的非瓣膜性房颤患者随机分为两组，一组接受剂量调整后的华法林治疗（国际标准化比值为2至3）（第一组），另一组接受阿司匹林75毫克和氯吡格雷75毫克的联合治疗（第二组）。在基线（治疗前）和治疗后六周，对血栓形成的血浆指标（纤维蛋白D - 二聚体、凝血酶原片段1 + 2）和血小板活化指标（β - 血小板球蛋白[TG]和可溶性P - 选择素）进行定量，并检测血小板对标准激动剂的聚集反应。结果：房颤患者治疗前纤维蛋白D - 二聚体（p = 0.001）、β - TG（p = 0.01）和可溶性P - 选择素（p = 0.03）水平升高，而血浆凝血酶原片段1 + 2水平和血小板聚集与对照组相比无显著差异。剂量调整后的华法林在六周时降低了血浆纤维蛋白D - 二聚体、凝血酶原片段1 + 2和β - 血小板球蛋白水平（均p < 0.001），提高了血浆可溶性P - 选择素水平（p < 0.001），对血小板聚集无显著影响。阿司匹林 - 氯吡格雷联合治疗对血栓形成或血小板活化的血浆标志物无影响（均p = 无显著性差异），但血小板对二磷酸腺苷（p < 0.001）和肾上腺素（p = 0.02）的聚集反应降低。
阿司匹林 - 氯吡格雷联合治疗未能降低房颤患者血栓形成和血小板活化的血浆指标，尽管体外血小板聚集的某些方面发生了改变。在房颤血栓预防方面，华法林抗凝可能优于阿司匹林 - 氯吡格雷联合治疗。
