Effect of dipyridamole plus aspirin on hemodialysis graft patency.
BACKGROUND
Arteriovenous graft stenosis leading to thrombosis is a major cause of complications in patients undergoing hemodialysis. Procedural interventions may restore patency but are costly. Although there is no proven pharmacologic therapy, dipyridamole may be promising because of its known vascular antiproliferative activity.


METHODS
We conducted a randomized, double-blind, placebo-controlled trial of extended-release dipyridamole, at a dose of 200 mg, and aspirin, at a dose of 25 mg, given twice daily after the placement of a new arteriovenous graft until the primary outcome, loss of primary unassisted patency (i.e., patency without thrombosis or requirement for intervention), was reached. Secondary outcomes were cumulative graft failure and death. Primary and secondary outcomes were analyzed with the use of a Cox proportional-hazards regression with adjustment for prespecified covariates.


RESULTS
At 13 centers in the United States, 649 patients were randomly assigned to receive dipyridamole plus aspirin (321 patients) or placebo (328 patients) over a period of 4.5 years, with 6 additional months of follow-up. The incidence of primary unassisted patency at 1 year was 23% (95% confidence interval [CI], 18 to 28) in the placebo group and 28% (95% CI, 23 to 34) in the dipyridamole-aspirin group, an absolute difference of 5 percentage points. Treatment with dipyridamole plus aspirin significantly prolonged the duration of primary unassisted patency (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P=0.03) and inhibited stenosis. The incidences of cumulative graft failure, death, the composite of graft failure or death, and serious adverse events (including bleeding) did not differ significantly between study groups.


CONCLUSIONS
Treatment with dipyridamole plus aspirin had a significant but modest effect in reducing the risk of stenosis and improving the duration of primary unassisted patency of newly created grafts. (ClinicalTrials.gov number, NCT00067119.)
Dixon
Bradley S
BS
University of Iowa College of Medicine and the Veterans Affairs Medical Center, Iowa City, IA 52242-1081, USA. bradley-dixon@uiowa.edu
Beck
Gerald J
GJ
Vazquez
Miguel A
MA
Greenberg
Arthur
A
Delmez
James A
JA
Allon
Michael
M
Dember
Laura M
LM
Himmelfarb
Jonathan
J
Gassman
Jennifer J
JJ
Greene
Tom
T
Radeva
Milena K
MK
Davidson
Ingemar J
IJ
Ikizler
T Alp
TA
Braden
Gregory L
GL
Fenves
Andrew Z
AZ
Kaufman
James S
JS
Cotton
James R
JR
Martin
Kevin J
KJ
McNeil
James W
JW
Rahman
Asif
A
Lawson
Jeffery H
JH
Whiting
James F
JF
Hu
Bo
B
Meyers
Catherine M
CM
Kusek
John W
JW
Feldman
Harold I
HI
D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004176:Dipyridamole / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006083:Graft Occlusion, Vascular / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D006435:Renal Dialysis / Q000009:adverse effects; D013927:Thrombosis / Q000453:epidemiology / Q000517:prevention & control*
D003692:Delayed-Action Preparations; D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D001241:Aspirin