What is the Optimal Antithrombotic Strategy in Patients With Atrial Fibrillation Undergoing PCI? (WOEST-3)
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| ClinicalTrials.gov Identifier: NCT04436978 |
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Recruitment Status :
Recruiting
First Posted : June 18, 2020
Last Update Posted : December 15, 2023
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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.
| Condition or disease | Intervention/treatment | Phase |
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| Acute Coronary Syndrome Myocardial Infarction Atrial Fibrillation Atrial Flutter STEMI - ST Elevation Myocardial Infarction NSTEMI - Non-ST Segment Elevation MI Bleeding Stroke Stent Thrombosis Embolism Coronary Artery Disease | Drug: 30-day DAPT Drug: Guideline-directed therapy | Phase 4 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 2000 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | The study is designed as a multicentre open label randomized controlled superiority trial with regards to safety and non-inferiority trial with regards to efficacy. Participating study centres will enrol patients undergoing PCI who have previously or newly diagnosed AF and indication for NOAC. As soon as possible, but within 72 hours after PCI, patients will be randomized 1:1 to either
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| Masking: | Single (Outcomes Assessor) |
| Primary Purpose: | Prevention |
| Official Title: | What is the Optimal Antithrombotic Strategy in Patients With Atrial Fibrillation Having Acute Coronary Syndrome or Undergoing Percutaneous Coronary Intervention? |
| Actual Study Start Date : | January 11, 2023 |
| Estimated Primary Completion Date : | October 1, 2027 |
| Estimated Study Completion Date : | December 1, 2027 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: First month DAPT
30-day DAPT (aspirin + P2Y12 inhibitor). After 30 days all patients will be treated with edoxaban and P2Y12 inhibitor. Selection of P2Y12 inhibitor is at the discretion of the treating physician, depending on both bleeding and ischemic risk. Dosage of aspirin and P2Y12 inhibitor is according to local guidelines. NOAC of choice will be edoxaban. Patients will be treated with the recommended dose of 60mg once daily or the reduced dose of 30mg once daily. |
Drug: 30-day DAPT
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. |
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Active Comparator: Guideline-directed therapy
Standard guideline-directed therapy (edoxaban + P2Y12 inhibitor, aspirin limited to in-hospital use or up to 30 days in selected high-risk patients). After 30 days all patients will be treated with edoxaban and P2Y12 inhibitor. Selection of P2Y12 inhibitor is at the discretion of the treating physician, depending on both bleeding and ischemic risk. Dosage of aspirin and P2Y12 inhibitor is according to local guidelines. NOAC of choice will be edoxaban. Patients will be treated with the recommended dose of 60mg once daily or the reduced dose of 30mg once daily. |
Drug: Guideline-directed therapy
Guideline-directed therapy (edoxaban + P2Y12 inhibitor, aspirin limited to in-hospital use or up to 30 days in selected high-risk patients) |
- Primary safety endpoint [ Time Frame: 6 weeks ]Major or clinically relevant non-major bleeding as defined by the International Society of Thrombosis and Haemostasis
- Primary efficacy endpoint [ Time Frame: 6 weeks ]Composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis
- Bleeding complications [ Time Frame: 6 months ]Major or clinically relevant non-major bleeding as defined by the International Society of Thrombosis and Haemostasis
- Thrombotic complications [ Time Frame: 6 months ]Composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis
- 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
- Clinical symptom severity [ Time Frame: 6 weeks, 3 months, 6 months ]CCS grade
- All-cause death [ Time Frame: 6 weeks, 3 months, 6 months ]All-cause death as defined by ARC-2 and SCTI
- Myocardial infarction [ Time Frame: 6 weeks, 3 months, 6 months ]Myocardial infarction as defined by the 4th Universal Definition of Myocardial Infarction
- Stroke [ Time Frame: 6 weeks, 3 months, 6 months ]Stroke as defined by VARC-2 definitions
- Systemic embolism [ Time Frame: 6 weeks, 3 months, 6 months ]Systemic embolism according to ENTRUST-AF PCI definition
- Stent thrombosis [ Time Frame: 6 weeks, 3 months, 6 months ]Stent thrombosis as defined by ARC-2
- Major bleeding [ Time Frame: 6 weeks, 3 months, 6 months ]Major bleeding as defined by BARC 3 or 5
- Clinically relevant non-major bleeding [ Time Frame: 6 weeks, 3 months, 6 months ]CRNM as defined by BARC 2
- Quality of life as assessed by the EuroQol-5D-5L questionnaire [ Time Frame: 6 weeks, 3 months, 6 months ]EuroQol-5D-5L questionnaire
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04436978
| Contact: Ashley Verburg, MD | +31 (0)88 320 0925 | as.verburg@antoniusziekenhuis.nl |
Show 20 study locations
| Principal Investigator: | Jurriën M ten Berg, Prof, MD | St. Antonius Hospital |
| Responsible Party: | Jurriën M. ten Berg, MD, PhD, Professor dr., St. Antonius Hospital |
| ClinicalTrials.gov Identifier: | NCT04436978 |
| Other Study ID Numbers: |
NL81102.100.22 2022-001298-30 ( EudraCT Number ) |
| First Posted: | June 18, 2020 Key Record Dates |
| Last Update Posted: | December 15, 2023 |
| Last Verified: | December 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Will individual participant data be available? Yes What data in particular will be shared? Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices). What other documents will be available? Study Protocol, informed consent form, clinical study report When will data be available (start and end dates)? Within 1 year following article publication. End date to be determined. With whom? Researchers who provide a methodologically sound proposal. For what types of analyses? To achieve aims in the approved proposal. By what mechanism will data be made available? Proposals should be directed to as.verburg@antoniusziekenhuis.nl. To gain access, data requestors will need to sign a data access agreement. |
| Supporting Materials: |
Study Protocol Informed Consent Form (ICF) Clinical Study Report (CSR) |
| Time Frame: | Within 1 year following article publication. End date to be determined. |
| Access Criteria: | Researchers who provide a methodologically sound proposal. |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Acute Coronary Syndrome Myocardial Infarction Atrial Fibrillation Atrial Flutter STEMI - ST Elevation Myocardial Infarction NSTEMI - Non-ST Segment Elevation MI Oral Anticoagulant NOAC - Novel Oral Anticoagulant DOAC - Direct Oral Anticoagulant DAPT - Dual Antiplatelet Therapy |
Antithrombotic Therapy Dual Therapy Triple Therapy Bleeding Thrombosis Stroke Stent Thrombosis Systemic Embolism Percutaneous coronary intervention Coronary artery disease |
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Atrial Fibrillation Coronary Artery Disease Myocardial Ischemia Coronary Disease Myocardial Infarction Thrombosis Acute Coronary Syndrome Embolism ST Elevation Myocardial Infarction Atrial Flutter Syndrome Infarction |
Disease Pathologic Processes Vascular Diseases Cardiovascular Diseases Arrhythmias, Cardiac Heart Diseases Ischemia Necrosis Arteriosclerosis Arterial Occlusive Diseases Embolism and Thrombosis |