Effect of Clopidogrel on Early Failure of Arterial Venous Fistula for Hemodialysis: A Randomized, Controlled Trial

Abstract

Conclusion: Clopidogrel reduces early thrombosis of new arteriovenous fistulas but does not increase the proportion of fistulas that ultimately become suitable for dialysis. Summary: Antiplatelet agents may reduce thrombosis of newly created arteriovenous fistulas. Fistula thrombosis is one of a number of barriers to achieving autogenous access in patients requiring hemodialysis. In this study the authors sought to determine whether clopidogrel could reduce early failure of new fistulas created for hemodialysis access. This was a randomized, double-blind, placebo-controlled trial conducted at nine United States centers that represented both academic and community practices. The study period was from 2003 through 2007, during which 877 participants with advanced chronic kidney disease or end-stage renal disease were followed up until 150 to 180 days after fistula creation, or until 30 days after initiation of dialysis, whichever occurred later. Participants were randomly assigned to receive clopidogrel or placebo. Clopidogrel-treated patients received a 300-mg loading dose, followed by a daily dose of 75 mg (n = 441). The drugs were administered for 6 weeks, starting ≤1 day after fistula creation. The primary outcome was fistula thrombosis determined by physical examination at 6 weeks. The secondary outcome was failure of the fistula to become suitable for dialysis. Suitability for dialysis was defined as the fistula providing 300 mL/min of flow during 8 of 12 dialysis sessions. Based on the stopping rule for intervention efficacy, enrollment in the study was stopped after 877 patients had been randomized. Fistula thrombosis occurred in 53 (12.3%) of those assigned to clopidogrel compared with 85 (19.5%) of those assigned to placebo (relative risk, 0.63; 95% confidence interval, 0.46-0.97, P = .018). There was, however, no difference in failure to attain suitability for dialysis in the clopidogrel and placebo groups, at 61.8% vs 59.5% respectively (relative risk, 1.05; 95% confidence interval, 0.94-1.17; P = .40). There was no increase in bleeding events with the use of clopidogrel. Comment: Obviously, early patency is necessary for fistula maturation. However, there are clearly other aspects of fistula maturation required for the fistula to ultimately be useful for dialysis. Distal stenoses in the draining vein and poor arterial inflow can limit successful fistula maturation despite the use of an antiplatelet agent to prevent early thrombosis. Another key to fistula maturation may be surgical judgment. This study will be limited in its effect by the high rate of fistula failure that was observed. The trial points out the need to identify other mechanisms for failure of fistula maturation and for improved criteria for selecting candidates for fistula creation.