Effect of clopidogrel on early failure of arteriovenous fistulas for hemodialysis: a randomized controlled trial

JAMA. 2008 May 14;299(18):2164-71. doi: 10.1001/jama.299.18.2164.

Abstract

Context: The arteriovenous fistula is the preferred type of vascular access for hemodialysis because of lower thrombosis and infection rates and lower health care expenditures compared with synthetic grafts or central venous catheters. Early failure of fistulas due to thrombosis or inadequate maturation is a barrier to increasing the prevalence of fistulas among patients treated with hemodialysis. Small, inconclusive trials have suggested that antiplatelet agents may reduce thrombosis of new fistulas.

Objective: To determine whether clopidogrel reduces early failure of hemodialysis fistulas.

Design, setting, and participants: Randomized, double-blind, placebo-controlled trial conducted at 9 US centers composed of academic and community nephrology practices in 2003-2007. Eight hundred seventy-seven participants with end-stage renal disease or advanced chronic kidney disease were followed up until 150 to 180 days after fistula creation or 30 days after initiation of dialysis, whichever occurred later.

Intervention: Participants were randomly assigned to receive clopidogrel (300-mg loading dose followed by daily dose of 75 mg; n = 441) or placebo (n = 436) for 6 weeks starting within 1 day after fistula creation.

Main outcome measures: 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 was defined as use of the fistula at a dialysis machine blood pump rate of 300 mL/min or more during 8 of 12 dialysis sessions.

Results: Enrollment was stopped after 877 participants were randomized based on a stopping rule for intervention efficacy. Fistula thrombosis occurred in 53 (12.2%) participants assigned to clopidogrel compared with 84 (19.5%) participants assigned to placebo (relative risk, 0.63; 95% confidence interval, 0.46-0.97; P = .018). Failure to attain suitability for dialysis did not differ between the clopidogrel and placebo groups (61.8% vs 59.5%, respectively; relative risk, 1.05; 95% confidence interval, 0.94-1.17; P = .40).

Conclusion: Clopidogrel reduces the frequency of early thrombosis of new arteriovenous fistulas but does not increase the proportion of fistulas that become suitable for dialysis. Trial Registration clinicaltrials.gov Identifier: NCT00067119.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Arteriovenous Shunt, Surgical / adverse effects*
  • Clopidogrel
  • Double-Blind Method
  • Female
  • Graft Occlusion, Vascular / prevention & control*
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Renal Dialysis / methods*
  • Thrombosis / etiology*
  • Thrombosis / prevention & control*
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Vascular Patency

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine

Associated data

  • ClinicalTrials.gov/NCT00067119