Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial
Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial
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DOI：
10.1016/j.jvs.2010.04.027
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发表时间：
2010-10-01
影响因子：
4.3
通讯作者：
Dormandy, John
中科院分区：
文献类型：
--
作者：
Belch, Jill J. F.;Dormandy, John
目的：在急性冠脉综合征患者和接受经皮冠状动脉介入治疗的患者中，氯吡格雷联合乙酰水杨酸（阿萨）双重抗血小板治疗优于单用阿萨治疗的上级效果。我们试图确定在接受膝下旁路移植术的患者中，氯吡格雷联合阿萨是否比单独阿萨对肢体预后有益。接受单侧，在术后2 - 4天入组了20例接受膝下旁路移植术治疗动脉粥样硬化性外周动脉疾病（PAD）的患者，并随机分配至氯吡格雷75 mg/天+阿萨75 - 100 mg/天组。或安慰剂+阿萨75 - 100 mg/天，持续6 - 24个月。主要有效性终点为初次移植物闭塞或血运重建、患肢踝上截肢或死亡的复合终点。主要安全性终点为严重出血结果：在总体人群中，氯吡格雷组425例患者中有149例发生主要终点，安慰剂组426例患者中有151例发生主要终点（+阿萨）组（风险比[FIR]，0.98; 95%置信区间[CI]，0.78-1.23）。在预先设定的亚组分析中，氯吡格雷显著降低了人工血管移植患者的主要终点（HR，0.65; 95% CI，0.45-0.95; P = 0.025），但静脉移植患者的主要终点没有降低（HR，1.25; 95% CI，0.94-1.67，不显著[NS]）。观察到治疗效果和移植物类型之间存在显著的统计学相互作用（P-相互作用= 0.008）。虽然氯吡格雷组的总出血率更高，但氯吡格雷组和安慰剂组（加阿萨）的严重出血率无显著差异（2.1% vs 1.2%）。结论：氯吡格雷加阿萨联合用药并不能改善需要膝下旁路移植术的PAD患者的肢体或全身结局。亚组分析表明，氯吡格雷联合阿萨可使接受人工血管移植的患者获益，而不会显著增加大出血风险。（J Vase Surg 2010;52：825-33.）
Objective: Dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid (ASA) is superior to ASA alone in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention. We sought to determine whether clopidogrel plus ASA conferred benefit on limb outcomes over ASA alone in patients undergoing below-knee bypass grafting.Methods: Patients undergoing unilateral, below-knee bypass graft for atherosclerotic peripheral arterial disease (PAD) were enrolled 2 to 4 days after surgery and were randomly assigned to clopidogrel 75 mg/day plus ASA 75 to 100 mg/day or placebo plus ASA 75 to 100 mg/day for 6 to 24 months. The primary efficacy endpoint was a composite of index-graft occlusion or revascularization, above-ankle amputation of the affected limb, or death. The primary safety endpoint was severe bleeding (Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries [GUSTO] classification).Results: In the overall population, the primary endpoint occurred in 149 of 425 patients in the clopidogrel group vs 151 of 426 patients in the placebo (plus ASA) group (hazard ratio [FIR], 0.98; 95% confidence interval [CI], 0.78-1.23). In a prespecified subgroup analysis, the primary endpoint was significantly reduced by clopidogrel in prosthetic graft patients (HR, 0.65; 95% CI, 0.45-0.95; P = .025) but not in venous graft patients (HR, 1.25; 95% CI, 0.94-1.67, not significant [NS]). A significant statistical interaction between treatment effect and graft type was observed (P-interaction =.008). Although total bleeds were more frequent with clopidogrel, there was no significant difference between the rates of severe bleeding in the clopidogrel and placebo (plus ASA) groups (2.1% vs 1.2%).Conclusion: The combination of clopidogrel plus ASA did not improve limb or systemic outcomes in the overall population of PAD patients requiring below-knee bypass grafting. Subgroup analysis suggests that clopidogrel plus ASA confers benefit in patients receiving prosthetic grafts without significantly increasing major bleeding risk. (J Vase Surg 2010;52:825-33.)