Dipyridamole, Aspirin Drug Aid Hemodialysis Treatment
A new study, led by a University of Iowa researcher, shows for the first time that the anti-clotting drug dipyridamole combined with aspirin delays the initial failure of arteriovenous vascular access grafts used in hemodialysis for patients with end-stage kidney disease.
A functioning vascular access allows blood to be removed for cleansing. Grafts typically fail due to blood vessel narrowing (stenosis) at the graft site, leading to clotting, which in turn blocks blood flow. A blocked graft cannot be used and is a major cause of worsening health for patients on dialysis.
The study was part of the Dialysis Access Consortium and funded by the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health. The study found that drug therapy with extended-release dipyridamole plus aspirin was safe and decreased by 5 percent the rate of arteriovenous vascular access grafts that had a first failure within one year.
"Access failure is the Achilles' heel of hemodialysis," said Brad Dixon, M.D., the study's principal investigator and associate professor of internal medicine at the UI Roy J. and Lucille A. Carver College of Medicine. "Although the benefit was modest, the investigation is the first study to date to show that a drug can reduce narrowing within arteriovenous grafts. Depending on cost-analysis, it might be worthwhile to use this treatment approach preventively."
More than 300,000 Americans with end-stage kidney disease receive hemodialysis several times a week. Each year, approximately one in three patients has a vascular access problem that requires hospitalization. Costs associated with vascular access maintenance are estimated to exceed $1 billion annually in the United States.
The preferred access method is the fistula, which is a direct connection between artery and vein, because it has the fewest complications. The second preferred method is the arteriovenous graft, which is a surgically inserted piece of tubing connecting an artery and a vein. The least preferred type is the catheter.
"A fistula does not work for some patients. A graft is the next best option, but they frequently clot. We wanted to try to find a drug-based, rather than a procedure-based, approach to prevent that from occurring," said Dixon, who also is a staff physician and researcher with the Iowa City Veterans Affairs Medical Center.
In 1995, a small, single-site study showed that dipyridamole, used with or without aspirin, prevents clotting in new grafts. The current multicenter study included 649 patients at 13 centers involving more than 45 community-based and university dialysis units nationwide. In addition to the UI, nearby participating sites included the Iowa City VA Medical Center, the Renal Care Group in Peoria, Ill., and Covenant Hospital in Waterloo.
Approximately 71 percent of participants were black, the average age was 58 and just over 60 percent were female. The study included individuals at higher risk for vascular access failure since lower-risk patients tend to receive a fistula. Participants already could be on aspirin, but the study was limited to patients with a lower risk of bleeding.
Nearly half of the 649 participants received a capsule containing 200 milligrams of extended-release dipyridamole plus 25 milligrams of aspirin, and half received placebo twice a day for up to four-and-half years. After one year, 72 percent of the active treatment group and 77 percent of the placebo group had suffered at least one thrombosis or access intervention, and in contrast to earlier studies of anti-clotting drugs, no excess risk of bleeding was seen.
"The overall high rate of failure in both groups is daunting. Procedures needed to correct these graft failures contribute to the high costs of dialysis treatment for grafts," Dixon said. "This study represents an important step towards understanding and treating the problem. The next step is to examine new treatments and combination therapy for hemodialysis vascular stenosis."
The cost of treating a patient for one year with this therapy would be between $500 and $2,200. Additional study is needed to determine whether treatment costs outweigh benefits for most patients.
The study included support from Boehringer Ingelheim Pharmaceuticals, which also provided the study drugs and matched placebo at no cost. The company was not involved in the study design, data analysis or manuscript preparation. Among the study co-authors (none at the UI), one received consulting fees, one received a grant and one received lecture fees from the pharmaceutical company.