{
  "abstract": "Objective The impact of off-label underdosing of direct oral anticoagulants (DOACs) on clinical outcomes in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) remains unclear.Methods The EPIC-CAD trial (Edoxaban vs Edoxaban with antiPlatelet agent In patients with atrial fibrillation and Chronic stable Coronary Artery Disease) randomised patients with AF and stable CAD to receive either edoxaban monotherapy or dual antithrombotic therapy (edoxaban plus single antiplatelet agent). Off-label underdosing was defined as low-dose edoxaban (30 mg once daily) without standard criteria for dose reduction. The primary outcome was a composite of death, myocardial infarction, stroke, systemic embolism, unplanned revascularisation and major or clinically relevant non-major bleeding at 12 months.Results Among the 1040 randomised patients, 694 patients (66.7%) without dose-reduction criteria were included; of whom, 121 patients (17.4%) received edoxaban underdosing. At 12 months, the incidence of primary outcome was similar between standard-dose and under-dose edoxaban groups (10.5% vs 9.2%, adjusted HR 0.77, 95% CI 0.39 to 1.54). There was no significant difference in major ischaemic events (1.4% vs 1.7%, HR 1.14, 95% CI 0.22 to 5.91) and major or clinically relevant non-major bleeding (9.0% vs 8.4%, HR 0.87, 95% CI 0.42 to 1.78). Regardless of edoxaban underdosing, edoxaban monotherapy was associated with lower risk of primary net-clinical outcomes and bleeding compared with dual antithrombotic therapy.Conclusions In patients with AF and stable CAD, there was no significant difference in the rate of primary outcome between off-label underdose and standard-dose edoxaban. The benefit of edoxaban monotherapy over dual antithrombotic therapy was consistent regardless of edoxaban underdosing. However, given the analyses were underpowered and the CI was wide, the results cannot be considered clinically directive.Trial registration number URL: https://www.clinicaltrials.gov; unique identifiers: NCT03718559.",
  "authors": [
    {
      "affiliations": [
        "Heart Institute, Asan Medical Center, Seoul, Korea (the Republic of)"
      ],
      "name": "Min Soo Cho"
    },
    {
      "affiliations": [
        "Asan Medical Center, Seoul, Korea (the Republic of)"
      ],
      "name": "Do-Yoon Kang"
    },
    {
      "affiliations": [
        "Asan Medical Center, Seoul, Korea (the Republic of)"
      ],
      "name": "Jung-Bok Lee"
    },
    {
      "affiliations": [
        "The Catholic University of Korea Seoul St Mary’s Hospital, Seoul, Korea (the Republic of)"
      ],
      "name": "Yong-Seog Oh"
    },
    {
      "affiliations": [
        "Veterans Health Service Medical Centre, Seoul, Korea (the Republic of)"
      ],
      "name": "Chang Hoon Lee"
    },
    {
      "affiliations": [
        "Seoul National University Hospital, Seoul, Korea (the Republic of)"
      ],
      "name": "Eue-Keun Choi"
    },
    {
      "affiliations": [
        "Cardiology, Bundang Seoul National University Hospital Department of Internal Medicine, Seongnam, Korea (the Republic of)"
      ],
      "name": "Ji Hyun Lee"
    },
    {
      "affiliations": [
        "Cardiology, Konkuk University Medical Center, Seoul, Korea (the Republic of)"
      ],
      "name": "Chang Hee Kwon"
    },
    {
      "affiliations": [
        "Cardiology, Ulsan University Hospital, Ulsan, Korea (the Republic of)"
      ],
      "name": "Gyung-Min Park"
    },
    {
      "affiliations": [
        "Cardiology, Soonchunhyang University Hospital, Bucheon, Korea (the Republic of)"
      ],
      "name": "Hyung Oh Choi"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Cardiology, Hallym University Medical Center, Anyang, Korea (the Republic of)"
      ],
      "name": "Kyoung-Ha Park"
    },
    {
      "affiliations": [
        "Department of Medicine, Samsung Medical Center, Seoul, Korea (the Republic of)"
      ],
      "name": "Kyoung-Min Park"
    },
    {
      "affiliations": [
        "Keimyung University Dongsan Hospital, Daegu, Korea (the Republic of)"
      ],
      "name": "Jongmin Hwang"
    },
    {
      "affiliations": [
        "Internal Medicine, Catholic University of Korea Saint Vincent’s Hospital, Suwon, Korea (the Republic of)"
      ],
      "name": "Ki-Dong Yoo"
    },
    {
      "affiliations": [
        "Dong-A University Medical Center, Dong-A University College of Medicine, Busan, Korea (the Republic of)"
      ],
      "name": "Young Rak Cho"
    },
    {
      "affiliations": [
        "Internal medicine, Dongguk University Ilsan Hospital, Goyang, Korea (the Republic of)"
      ],
      "name": "Ji-Hyun Kim"
    },
    {
      "affiliations": [
        "Pusan National University Yangsan Hospital, Yangsan, Korea (the Republic of)"
      ],
      "name": "Ki Won Hwang"
    },
    {
      "affiliations": [
        "Kyung Hee University Gangdong Hospital, Seoul, Korea (the Republic of)"
      ],
      "name": "Eun Sun Jin"
    },
    {
      "affiliations": [
        "Cardiology, The Catholic University of Korea Eunpyeong St Mary’s Hospital, Seoul, Korea (the Republic of)"
      ],
      "name": "Osung Kwon"
    },
    {
      "affiliations": [
        "Haeundae Paik Hospital, Busan, Korea (the Republic of)"
      ],
      "name": "Ki-Hun Kim"
    },
    {
      "affiliations": [
        "Department of Cardiology, University of Ulsan College of Medicine, Seoul, Korea (the Republic of)"
      ],
      "name": "Duk-Woo Park"
    },
    {
      "affiliations": [
        "Department of Cardiology, University of Ulsan College of Medicine, Seoul, Korea (the Republic of)"
      ],
      "name": "Gi-Byoung Nam"
    },
    {
      "affiliations": [],
      "name": "on the behalf of the EPIC-CAD Investigators"
    }
  ],
  "title": "Off-label underdosing of edoxaban antithrombotic therapy for patients with atrial fibrillation and stable coronary artery disease: findings from the EPIC-CAD trial",
  "uid": "c8e2e885-eb21-5967-b30a-eda7fca5f7e7"
}