title: A review of antithrombotic therapy and the rationale and design of the randomized edoxaban in patients with peripheral artery disease (ePAD) trial adding edoxaban or clopidogrel to aspirin after femoropopliteal endovascular intervention.
abstract: Compared with the coronary setting, knowledge about antithrombotic therapies after endovascular treatment (EVT) is inadequate in patients with peripheral artery disease (PAD). Based on a review of trials and guidelines, which is summarized in this article, there is scant evidence that antithrombotic drugs improve outcome after peripheral EVT. To address this knowledge gap, the randomized, open-label, multinational edoxaban in patients with Peripheral Artery Disease (ePAD) study (ClinicalTrials.gov identifier NCT01802775) was designed to explore the safety and efficacy of a combined regimen of antiplatelet therapy with clopidogrel and anticoagulation with edoxaban, a selective and direct factor Xa inhibitor, both combined with aspirin. As of July 2014, 203 patients (144 men; mean age 67 years) from 7 countries have been enrolled. These patients have been allocated to once-daily edoxaban [60 mg for 3 months (or 30 mg in the presence of factors associated with increased exposure)] or clopidogrel (75 mg/d for 3 months). All patients received aspirin (100 mg/d) for the 6-month duration of the study. The primary safety endpoint is major or clinically relevant nonmajor bleeding; the primary efficacy endpoint is restenosis or reocclusion at the treated segment(s) measured at 1, 3, and 6 months using duplex ultrasound scanning. All outcomes will be assessed and adjudicated centrally in a masked fashion. The ePAD study is the first of its kind to investigate a combined regimen of antiplatelet therapy and anticoagulation through factor Xa inhibition with edoxaban.
authors: University Medical Center Utrecht, the Netherlands m.tangelder@umcutrecht.nl.
authors: Marco J D
authors: MJ
authors: Tangelder
authors: Daiichi Sankyo Pharma Development, Edison, NJ, USA.
authors: Chuke E
authors: CE
authors: Nwachuku
authors: Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors: Michael
authors: M
authors: Jaff
authors: Swiss Cardiovascular Center, University Hospital Bern, Switzerland.
authors: Iris
authors: I
authors: Baumgartner
authors: Daiichi Sankyo Pharma Development, Edison, NJ, USA.
authors: Anil
authors: A
authors: Duggal
authors: Rex Healthcare, University of North Carolina Health Systems, Raleigh, NC, USA.
authors: George
authors: G
authors: Adams
authors: Riverside Methodist Hospital, Columbus, OH, USA.
authors: Gary
authors: G
authors: Ansel
authors: Daiichi Sankyo Pharma Development, Edison, NJ, USA.
authors: Michael
authors: M
authors: Grosso
authors: Daiichi Sankyo Pharma Development, Edison, NJ, USA.
authors: Michele
authors: M
authors: Mercuri
authors: Daiichi Sankyo Pharma Development, Edison, NJ, USA.
authors: Minggao
authors: M
authors: Shi
authors: Vienna General Hospital, Medical University of Vienna, Austria.
authors: Erich
authors: E
authors: Minar
authors: University Medical Center Utrecht, the Netherlands.
authors: Frans L
authors: FL
authors: Moll
mesh_terms: D000368:Aged; D017130:Angioplasty / Q000009:adverse effects / Q000295:instrumentation; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005060:Europe; D065427:Factor Xa Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005263:Femoral Artery / Q000503:physiopathology; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007557:Israel; D008297:Male; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011150:Popliteal Artery / Q000503:physiopathology; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D012107:Research Design; D012307:Risk Factors; D015607:Stents; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D013844:Thiazoles; D000077144:Clopidogrel; C552171:edoxaban; D013988:Ticlopidine; D001241:Aspirin
keywords: angioplasty; antiplatelet therapy; antithrombotic therapy; aspirin; bleeding; clopidogrel; edoxaban; endovascular therapy; factor Xa inhibitor; femoropopliteal segment; peripheral artery disease; randomized controlled trial; restenosis; stent