The long-term objective of this proposal is to establish whether or not the use of dipyridamole is efficacious in improving the function of expanded polytetrafluoroethylene (ePTFE) grafts used for dialysis access in patients with end stage renal disease on chronic hemodialysis therapy. Currently, there are over 170,000 patients in the US on chronic hemodialysis therapy. For these patients, problems with vascular access patency have been called the """"""""Achilles Heel"""""""" of the dialysis procedure. Furthermore, the development of ePTFE graft stenosis and thrombosis reduces the quality of delivered dialysis therapy and increases the infection risk for patients on dialysis. Maintaining vascular access patency costs approximately $7,871 per hemodialysis patient per year at risk with an estimated annual global cost of more than one billion dollars. Recent evidence suggests that in almost all cases, ePTFE graft thrombosis occurs only after the development of a stenosis either at the graft vein anastomosis or more distally in the vein. These venous stenoses occur because of a pathological process known as intimal hyperplasia. Recent evidence from a small, single-center, prospective, randomized, placebo-controlled clinical trial has suggested that dipyridamole may reduce the rate of ePTFE graft thrombosis in chronic hemodialysis patients. The mechanism of dipyridamole efficacy may be by inhibiting vascular smooth muscle cell proliferation and thereby reducing the development of intimal hyperplasia and associated venous stenoses.
The specific aims of this proposal are: l) To investigate the efficacy of dipyridamole in preventing the development of anastomotic and venous stenoses in patients on chronic hemodialysis with ePTFE grafts; and 2) To investigate the efficacy of dipyridamole in preventing the development of thrombosis in patients on chronic hemodialysis with new ePTFE grafts. In order to answer the Specific Aims, the proposed study design is a randomized, prospective, double-blind, placebo-controlled, parallel group clinical trial. Patients on chronic hemodialysis therapy who require a new prosthetic ePTFE graft will be randomized to receive either dipyridamole or placebo for a period of 12 months after enrollment or until ePTFE graft failure. Enrolled patients will undergo serial monitoring of vascular access blood flow, known to be a physiologic predictor of impending vascular access failure, with clinically indicated interventions to prevent vascular access failure. The study design will test the null hypothesis that dipyridamole does not affect the development of either venous stenosis or thrombosis in new ePTFE grafts in hemodialysis patients.
