The study, supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health, will be published in the May 21, 2009, New England Journal of Medicine.
Artery-vein access grafts, called arteriovenous (AV) grafts, fail most often due to narrowing of blood vessels (stenosis) at the graft site and subsequent clotting, which block the flow of blood. A blocked graft cannot be used for dialysis and is a major cause of worsening health in dialysis patients.
The DAC trial found that the combination treatment decreased the rate of loss of primary unassisted graft patency - the useful life of a graft before it becomes blocked the first time - by 18% and the rate of developing significant stenosis by 28%, compared to placebo. Previous smaller clinical trials of anti-clotting therapies failed to show that these drugs improve AV graft patency or that they could be used safely in dialysis patients.
"This drug combination provides a modest but important new therapy to keep AV grafts in good working order so patients can get the dialysis they need," said NIDDK Director Griffin P. Rodgers, M.D. "But clearly more research is needed to extend the useful life of AV grafts."
A total of 649 participants with new AV grafts were recruited for the trial at 13 clinical sites in the United States and were randomly assigned to treatment with dipyridamole plus aspirin or to a placebo. The trial took place over a period of five years.
"Our trial results show that we now have a drug therapy that significantly prolongs the viability of AV grafts," said Bradley S. Dixon, M.D., of the University of Iowa College of Medicine, Iowa City, and lead author of the study. "This is an important step forward as we proceed to develop therapies to improve dialysis patients" quality of life."
According to the 2008 U.S. Renal Data System Annual Data Report, more than half a million patients have kidney failure, 70% of whom are on dialysis. Costs for kidney failure are more than US$30 billion. Annual costs of vascular access-related procedures in the United States have been estimated to exceed US$1 billion. For more information on vascular access, visit: http://kidney.niddk.nih.gov/kudiseases/pubs/vascularaccess/index.htm.
For more information on this DAC study, go to www.clinicaltrials.gov/ct2/search and type NCT00067119 in the search window.
Boehringer Ingelheim Pharmaceuticals, Inc. provided the study drugs and placebo at no cost and provided additional funding as well. The company was not involved in the design of the study, the analysis of data, or the preparation of the manuscript.
The NIDDK established the multi-centre Dialysis Access Consortium in September 2000 to design and implement a series of randomized, controlled, clinical trials over a five-year period to identify effective therapies to reduce the rate of graft and fistula failure in dialysis patients. Participating institutions are Boston University, University of Iowa, Duke University, Maine Medical Centre, University of Alabama, University of Texas Southwestern Medical School, Washington University, and Cleveland Clinic Foundation.
