Kaufman James S, O'Connor Theresa Z, Zhang Jane Hongyuan, Cronin Robert E, Fiore Louis D, Ganz Michael B, Goldfarb David S, Peduzzi Peter N
Department of Veterans Affairs Boston Healthcare System and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02130, USA.
J Am Soc Nephrol. 2003 Sep;14(9):2313-21. doi: 10.1097/01.asn.0000081661.10246.33.
Thrombosis of hemodialysis vascular access grafts represents a major medical and economic burden. Experimental and clinical models suggest a role for antiplatelet agents in the prevention of thrombosis. The study was designed to determine the efficacy of the combination of aspirin and clopidogrel in the prevention of graft thrombosis. The study was a randomized, double-blind trial conducted at 30 hemodialysis units at Veterans Affairs medical centers. Participants undergoing hemodialysis with a polytetrafluoroethylene graft in the arm were randomized to receive either double placebos or aspirin (325 mg) and clopidogrel (75 mg) daily. Participants were to be monitored while receiving study medications for a minimum of 2 yr. The study was stopped after randomization of 200 participants, as recommended by the Data Safety and Monitoring Board because of a significantly increased risk of bleeding among the participants receiving aspirin and clopidogrel therapy. The cumulative incidence of bleeding events was significantly greater for those participants, compared with participants receiving placebos [hazard ratio, 1.98; 95% confidence interval (CI), 1.19 to 3.28; P = 0.007]. Twenty-three participants in the placebo group and 44 participants in the active treatment group experienced a bleeding event (P = 0.006). There was no significant benefit of active treatment in the prevention of thrombosis (hazard ratio, 0.81; 95% CI, 0.47 to 1.40; P = 0.45), although there was a trend toward a benefit among participants who had not experienced previous graft thrombosis (hazard ratio, 0.52; 95% CI, 0.22 to 1.26; P = 0.14). In the hemodialysis population, therapy with aspirin and clopidogrel was associated with a significantly increased risk of bleeding and probably would not result in a reduced frequency of graft thrombosis.
血液透析血管通路移植物血栓形成是一项重大的医学和经济负担。实验和临床模型表明抗血小板药物在预防血栓形成中发挥作用。本研究旨在确定阿司匹林和氯吡格雷联合用药预防移植物血栓形成的疗效。该研究是一项在退伍军人事务医疗中心的30个血液透析单位进行的随机双盲试验。接受上肢聚四氟乙烯移植物血液透析的参与者被随机分配，每天接受双安慰剂或阿司匹林（325毫克）和氯吡格雷（75毫克）治疗。参与者在接受研究药物治疗期间至少要监测2年。在随机分配了200名参与者后，该研究按照数据安全监测委员会的建议停止，因为接受阿司匹林和氯吡格雷治疗的参与者出血风险显著增加。与接受安慰剂的参与者相比，这些参与者出血事件的累积发生率显著更高[风险比，1.98；95%置信区间（CI），1.19至3.28；P = 0.007]。安慰剂组有23名参与者，活性治疗组有44名参与者发生了出血事件（P = 0.006）。活性治疗在预防血栓形成方面没有显著益处（风险比，0.81；95%CI，0.47至1.40；P = 0.45），尽管在既往未发生移植物血栓形成的参与者中有获益趋势（风险比，0.52；95%CI，0.22至1.26；P = 0.14）。在血液透析人群中，阿司匹林和氯吡格雷治疗与出血风险显著增加相关，可能不会降低移植物血栓形成的发生率。
