The risks for major bleeding and restenosis or reocclusion were similar with edoxaban plus aspirin compared with clopidogrel plus aspirin in patients who underwent endovascular therapy, according to data from the ePAD trial.
From 2012 to 2014, researchers randomly assigned 203 patients with symptomatic peripheral artery disease who underwent femoropopliteal endovascular therapy to aspirin plus edoxaban (Savaysa, Daiichi Sankyo; n = 101; mean age, 68 years; 67 men) or aspirin plus clopidogrel (n = 102; mean age, 66.7 years; 78 men).
The primary safety endpoint was bleeding as defined by TIMI and International Society on Thrombosis and Haemostasis (ISTH) criteria. According to TIMI criteria, there were no major or life-threatening bleeding events and five bleeding events classified as “any” in the edoxaban study arm compared with two major and two life-threatening bleeding events and nine bleeding events classified as “any” in the clopidogrel study arm. However, the difference in event rates did not reach statistical significance.
According to ISTH criteria, 11 major or clinically nonrelevant major bleeding events occurred in the edoxaban arm vs. eight in the clopidogrel arm — a difference that was also not statistically significant (RR = 1.39; 95% CI, 0.58-3.31) and remained nonsignificant after exclusion of vascular access bleeding.
In terms of major or life-threatening bleeding events only, two occurred in the edoxaban arm vs. seven in the clopidogrel arm (RR = 0.2; 95% CI, 0.02-1.7), with no significant change after exclusion of vascular access bleeding.
After 6 months, the incidence of the efficacy endpoint of restenosis or reocclusion was lower among patients treated with edoxaban vs. clopidogrel (30.9% vs. 34.7%; RR = 0.89; 95% CI, 0.59-2.34), as was the composite of restenosis or reocclusion and target lesion revascularization (33.7% vs. 41.2%; RR = 0.82; 95% CI, 0.53-1.18). Incidence of events after inclusion of MACE — nonfatal MI, nonfatal stroke and CV death — in the composite remained lower in the edoxaban arm vs. the clopidogrel arm (33.7% vs. 42.3%; RR = 0.8; 95% CI, 0.55-1.15). All differences, however, were not statistically significant, the researchers noted.
Ankle-brachial index after endovascular therapy was similar between groups. There were also no important changes in Rutherford category in either treatment arm.
At baseline, the mean lesion lengths were about 12 cm in both groups and 92% of the index lesions were in the femoral segment. More patients in the edoxaban arm than in the clopidogrel arm interrupted the study drug (27 vs. 15 patients) and more discontinued treatment permanently (22 vs. 7 patients). The edoxaban study arm also had fewer cumulative patient-years of treatment compared with the clopidogrel arm (21.7 vs. 23.9 years).
Study limitations included its open-label design and its small sample size, the researchers noted.
Although the results suggest that a combination of a novel oral anticoagulant, such as edoxaban, and aspirin could be beneficial after endovascular therapy in this patient population, an adequately powered, randomized trial is necessary before drawing firm conclusions, they wrote. – by Melissa Foster
Disclosures: The study was supported by Daiichi Sankyo. Four authors report they are employees of Daiichi Sankyo Pharma Development.