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


METHODS
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.


METHODS
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.


METHODS
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).


CONCLUSIONS
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.
Dember
Laura M
LM
Boston University, School of Medicine, Renal Section, EBRC 504, 650 Albany St, Boston, Massachusetts 02118, USA. ldember@bu.edu
Beck
Gerald J
GJ
Allon
Michael
M
Delmez
James A
JA
Dixon
Bradley S
BS
Greenberg
Arthur
A
Himmelfarb
Jonathan
J
Vazquez
Miguel A
MA
Gassman
Jennifer J
JJ
Greene
Tom
T
Radeva
Milena K
MK
Braden
Gregory L
GL
Ikizler
T Alp
TA
Rocco
Michael V
MV
Davidson
Ingemar J
IJ
Kaufman
James S
JS
Meyers
Catherine M
CM
Kusek
John W
JW
Feldman
Harold I
HI
D000328:Adult; D000368:Aged; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D000077144:Clopidogrel; D004311:Double-Blind Method; D005260:Female; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D006435:Renal Dialysis / Q000379:methods*; D013927:Thrombosis / Q000209:etiology* / Q000517:prevention & control*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014654:Vascular Patency
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine