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.