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NCT Number: NCT04436978

What is the Optimal Antithrombotic Strategy in Patients With Atrial Fibrillation Undergoing PCI?

The optimal antithrombotic management in patients with coronary artery disease (CAD) and concomitant atrial fibrillation (AF) is unknown. AF patients are treated with oral anticoagulation (OAC) to prevent ischemic stroke and systemic embolism and patients undergoing percutaneous coronary intervention (PCI) are treated with dual antiplatelet therapy (DAPT), i.e. aspirin plus P2Y12 inhibitor, to prevent stent thrombosis (ST) and myocardial infarction (MI). Patients with AF undergoing PCI were traditionally treated with triple antithrombotic therapy (TAT, i.e. OAC plus aspirin and P2Y12 inhibitor) to prevent ischemic complications. However, TAT doubles or even triples the risk of major bleeding complications. More recently, several clinical studies demonstrated that omitting aspirin, a strategy known as dual antithrombotic therapy (DAT) is safer compared to TAT with comparable efficacy.

However, pooled evidence from recent meta-analyses suggests that patients treated with DAT are at increased risk of MI and ST. Insights from the AUGUSTUS trial showed that aspirin added to OAC and clopidogrel for 30 days, but not thereafter, resulted in fewer severe ischemic events. This finding emphasizes the relevance of early aspirin administration on ischemic benefit, also reflected in the current ESC guideline. However, because we consider the bleeding risk of TAT unacceptably high, we propose to use a short course of DAPT (omitting OAC for 1 month). There is evidence from the BRIDGE study that a short period of omitting OAC is safe in patients with AF. In this study, these patients are treated with DAPT, which also prevents stroke, albeit not as effective as OAC. This temporary interruption of OAC will allow aspirin treatment in the first month post-PCI where the risk of both bleeding and stent thrombosis is greatest.

The WOEST 3 trial is a multicentre, open-label, randomised controlled trial investigating the safety and efficacy of one month DAPT compared to guideline-directed therapy consisting of OAC and P2Y12 inhibitor combined with aspirin up to 30 days. We hypothesise that the use of short course DAPT is superior in bleeding and non-inferior in preventing ischemic events. The primary safety endpoint is major or clinically relevant non-major bleeding as defined by the ISTH at 6 weeks after PCI. The primary efficacy endpoint is a composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis at 6 weeks after PCI.

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Key information

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients ≥ 18 years
  • Undergoing successful PCI (either ACS or elective PCI)
  • History of or newly diagnosed (<72 hours after PCI/ACS) atrial fibrillation or flutter with a long-term (≥ 1 year) indication for OAC

Exclusion criteria

  • Contra indication to edoxaban, aspirin or all P2Y12 inhibitors
  • Current indication for OAC besides atrial fibrillation/flutter (e.g. venous thromboembolism)
  • <12 months after any stroke
  • CHADSVASc score ≥7
  • Moderate to severe mitral valve stenosis (AVA ≤1.5 cm2)
  • Mechanical heart valve prosthesis
  • Intracardiac thrombus or apical aneurysm requiring OAC
  • Poor LV function (LVEF <30%) with proven slow-flow
  • History of intracranial haemorrhage
  • Active bleeding on randomization
  • History of intraocular, spinal, retroperitoneal, or traumatic intra-articular bleeding, unless the causative factor has been permanently resolved
  • Recent (<1 month) gastrointestinal haemorrhage, unless the causative factor has been permanently resolved.
  • Known coagulopathy
  • Severe anaemia requiring blood transfusion or thrombocytopenia <50 × 109/L
  • BMI >40 or bariatric surgery
  • Kidney failure (eGFR <15)
  • Active liver disease (ALT, ASP, AP >3x ULN or active hepatitis A, B or C)
  • Active malignancy excluding non-melanoma skin cancer
  • Life expectancy <1 year
  • Pregnancy or breast-feeding women

Treatment and study plan

30-day DAPT

Drug

DAPT (aspirin + P2Y12 inhibitor) during the first 30 days following PCI. After 30 days, all patients will be treated with edoxaban and a P2Y12 inhibitor.

Guideline-directed therapy

Drug

Guideline-directed therapy (edoxaban + P2Y12 inhibitor, aspirin limited to in-hospital use or up to 30 days in selected high-risk patients)

Primary outcomes

  1. Primary safety endpoint

    Time frame: 6 weeks

    Major or clinically relevant non-major bleeding as defined by the International Society of Thrombosis and Haemostasis

  2. Primary efficacy endpoint

    Time frame: 6 weeks

    Composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis

Secondary outcomes

  1. Bleeding complications

    Time frame: 6 months

    Major or clinically relevant non-major bleeding as defined by the International Society of Thrombosis and Haemostasis

  2. Thrombotic complications

    Time frame: 6 months

    Composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis

  3. Net clinical benefit

    Time frame: 6 weeks, 3 months, 6 months

    Composite of major bleeding, myocardial infarction, stroke, systemic embolism all-cause death and stent thrombosis

  4. Clinical symptom severity

    Time frame: 6 weeks, 3 months, 6 months

    CCS grade

  5. All-cause death

    Time frame: 6 weeks, 3 months, 6 months

    All-cause death as defined by ARC-2 and SCTI

  6. Myocardial infarction

    Time frame: 6 weeks, 3 months, 6 months

    Myocardial infarction as defined by the 4th Universal Definition of Myocardial Infarction

  7. Stroke

    Time frame: 6 weeks, 3 months, 6 months

    Stroke as defined by VARC-2 definitions

  8. Systemic embolism

    Time frame: 6 weeks, 3 months, 6 months

    Systemic embolism according to ENTRUST-AF PCI definition

  9. Stent thrombosis

    Time frame: 6 weeks, 3 months, 6 months

    Stent thrombosis as defined by ARC-2

  10. Major bleeding

    Time frame: 6 weeks, 3 months, 6 months

    Major bleeding as defined by BARC 3 or 5

  11. Clinically relevant non-major bleeding

    Time frame: 6 weeks, 3 months, 6 months

    CRNM as defined by BARC 2

Other outcomes

  1. Quality of life as assessed by the EuroQol-5D-5L questionnaire

    Time frame: 6 weeks, 3 months, 6 months

    EuroQol-5D-5L questionnaire

Study contacts

Contact information is provided by the study sponsor or research team.

Ashley Verburg, MD

CONTACT

[email protected]

+31 (0)88 320 0925

Sponsors and collaborators

Lead sponsor

St. Antonius Hospital

Other

Collaborators

  • Daiichi Sankyo

Registry information

Official study title

What is the Optimal Antithrombotic Strategy in Patients With Atrial Fibrillation Having Acute Coronary Syndrome or Undergoing Percutaneous Coronary Intervention?

Acronym: WOEST-3

Important dates

Study start
2023
Primary completion
2027
Study completion
2027
First posted
Jun 18, 2020
Registry last updated
Dec 15, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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