Effect of Antiplatelet Agents, Statins, and Other Drugs on Vascular Access Patency Rates

Abstract

The first randomized study investigating the effect of aspirin on access patency rates was published almost 4 decades ago. This study showed a beneficial effect of aspirin treatment on early access thrombosis. More recently, a nonrandomized population-based study, the Dialysis Outcomes and Practice Patterns Study (DOPPS), evaluated the effect of aspirin and other drugs on primary and secondary vascular access patency rates in patients with AV fistulae (n 1⁄4 900) or AV grafts (n 1⁄4 1944). Aspirin treatment was associated with a 30% improvement in secondary AV graft patency (relative risk [RR], 0.70; P < .001). A single-center, nonrandomized study verified the beneficial effect of aspirin and ticlopidine on dialysisassociated platelet deposition in polytetrafluoroethylene grafts. Finally, an independent double-blind randomized study reported a beneficial effect of clopidogrel (n 1⁄4 46 patients) on primary AV fistula failure rates compared with placebo (n 1⁄4 47 patients; 5.2% vs 21.6%, respectively; P 1⁄4 .03). A daily dosage of clopidogrel 75 mg beginning 7 to 10 days prior to AV fistula creation was recommended to prevent AV fistula thrombosis and failure without increasing the risk of bleeding episodes. A multicenter, randomized, double-blind, placebo-controlled trial involving 877 patients with AV fistula compared the effects of 300 mg loading dose followed by 75 mg/d clopidogrel (n 1⁄4 441) versus placebo (n 1⁄4 436) on AV fistula thrombosis rates at 6 weeks. This trial was prematurely stopped due to the apparent superiority of clopidogrel versus placebo on AV fistula thrombosis rates (12.2% vs 19.5%, respectively; RR, 0.63; 95% confidence interval [CI], 0.46-0.97; P1⁄4 .018). Similarly, a multicenter (n1⁄4 9) prospective, randomized study, the Swedish Fistula Study Group reported a 35% (although nonsignificant) risk reduction for early AV fistula occlusion by ticlopidine treatment compared with placebo (occlusion rate: 12% vs 19%, respectively). The US Renal Data System Dialysis Mortality and Morbidity Wave II Study reported contradictory results. Treatment with the antiplatelet agents ticlopidine and dipyridamole (hazard ratio [HR], 3.54; 95% CI, 1.07-11.76; P 1⁄4 .04), or aspirin (HR, 2.49; 95% CI, 1.31-4.73; P 1⁄4 .005) was associated with worse AV fistula patency rates compared with nonuse in this retrospective cohort study. Consistent antiplatelet use is mandatory to obtain optimal results. The DOPPS showed that consistent aspirin use over 1 year after AV fistula creation was associated with a 37% lower risk of final AV fistula failure (adjusted HR, 0.63; 95% CI, 0.42-0.95, P 1⁄4 .03). The presence of oxidative stress and inflammation accelerates neointima formation and thrombosis. Aspirin not only acts as an antiplatelet agent but also reduces oxidative stress and inflammation. Importantly double antiplatelet treatment with clopidogrel plus aspirin is not indicated due to an increased risk of bleeding. In cases when double antiplatelet treatment is required, combination of aspirin with dipyridamole may improve patency rates without increasing the bleeding episodes. A Cochrane systematic review evaluated the effect of antiplatelet treatment on vascular access patency rates. This review included 3 randomized trials with aspirin and another 3 with ticlopidine. Both aspirin and ticlopidine increased vascular access patency rates compared with placebo (odds ratio [OR], 0.42; 95% CI, 0.20-0.86; P 1⁄4 .02; and OR, 0.47; 95% CI, 0.26-0.85; P 1⁄4 .01, for aspirin and ticlopidine,