Randomized Controlled Trial of Clopidogrel plus Aspirin to Prevent Hemodialysis Access Graft Thrombosis

Abstract

ABSTRACT. 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. E-mail: james.kaufman@med.va.gov

Thrombophilia and Arteriovenous Fistula Survival in ESRD

“…These patients with hypercoagulable states or combined thrombophilia should be preoperatively identified to tailor antithrombotic therapy and intensify surveillance, especially during the first, most vulnerable months after surgery. However, the optimal prophylaxis for access thrombosis and stenosis is not settled despite extensive efforts (29)(30)(31)(32)(33)(34)(35).…”

Thrombophilia and the Risk for Hemodialysis Vascular Access Thrombosis

“…Because this was an observational study on risk factor identification, our data can provide no direct guidance on the prevention or treatment of access thrombosis. However, two recent randomized trials failed to show any benefit of low-intensity warfarin (46) or the combination of aspirin plus clopidogrel (47) in preventing access thrombosis. However, neither of these studies evaluated patients for thrombophilia.…”

Hemodialysis Vascular Access Dysfunction

“…There is no information on the placement of drug-eluting stents in patients with dialysis grafts and fistulae, although a recent study in a pig model of arteriovenous graft stenosis demonstrated an improvement in luminal stenosis at 28 d when sirolimus-eluting stents, as compared with bare-metal stents, were placed at the time of surgery (95). One potential disadvantage of drug-eluting stents in the hemodialysis population could be an increased risk for bleeding if both aspirin and clopidogrel are required after stent placement (96).…”