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RECRUITINGPhase 4INTERVENTIONAL

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

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

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Patients ≥ 18 years 2. Undergoing successful PCI (either ACS or elective PCI) 3. History of or newly diagnosed (\<72 hours after PCI/ACS) atrial fibrillation or flutter with a long-term (≥ 1 year) indication for OAC Who Should NOT Join This Trial: 1. Contra indication to edoxaban, aspirin or all P2Y12 inhibitors 2. Current indication for OAC besides atrial fibrillation/flutter (e.g. venous thromboembolism) 3. \<12 months after any stroke 4. CHADSVASc score ≥7 5. Moderate to severe mitral valve stenosis (AVA ≤1.5 cm2) 6. Mechanical heart valve prosthesis 7. Intracardiac thrombus or apical aneurysm requiring OAC 8. Poor LV function (LVEF \<30%) with proven slow-flow 9. History of intracranial haemorrhage 10. Active bleeding on randomization 11. History of intraocular, spinal, retroperitoneal, or traumatic intra-articular bleeding, unless the causative factor has been permanently resolved 12. Recent (\<1 month) gastrointestinal haemorrhage, unless the causative factor has been permanently resolved. 13. Known coagulopathy 14. Severe anaemia requiring blood transfusion or thrombocytopenia \<50 × 109/L 15. BMI \>40 or bariatric surgery 16. Kidney failure (eGFR \<15) 17. Active liver disease (ALT, ASP, AP \>3x ULN or active hepatitis A, B or C) 18. Active malignancy excluding non-melanoma skin cancer 19. Life expectancy \<1 year 20. Pregnancy or breast-feeding women Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: 1. Patients ≥ 18 years 2. Undergoing successful PCI (either ACS or elective PCI) 3. 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: 1. Contra indication to edoxaban, aspirin or all P2Y12 inhibitors 2. Current indication for OAC besides atrial fibrillation/flutter (e.g. venous thromboembolism) 3. \<12 months after any stroke 4. CHADSVASc score ≥7 5. Moderate to severe mitral valve stenosis (AVA ≤1.5 cm2) 6. Mechanical heart valve prosthesis 7. Intracardiac thrombus or apical aneurysm requiring OAC 8. Poor LV function (LVEF \<30%) with proven slow-flow 9. History of intracranial haemorrhage 10. Active bleeding on randomization 11. History of intraocular, spinal, retroperitoneal, or traumatic intra-articular bleeding, unless the causative factor has been permanently resolved 12. Recent (\<1 month) gastrointestinal haemorrhage, unless the causative factor has been permanently resolved. 13. Known coagulopathy 14. Severe anaemia requiring blood transfusion or thrombocytopenia \<50 × 109/L 15. BMI \>40 or bariatric surgery 16. Kidney failure (eGFR \<15) 17. Active liver disease (ALT, ASP, AP \>3x ULN or active hepatitis A, B or C) 18. Active malignancy excluding non-melanoma skin cancer 19. Life expectancy \<1 year 20. Pregnancy or breast-feeding women

Treatments Being Tested

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.

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)

Locations (20)

ASZ Aalst
Aalst, Belgium
UZ Antwerpen
Antwerp, Belgium
Imelda Ziekenhuis
Bonheiden, Belgium
UZ Brussel
Brussels, Belgium
Ziekenhuis Oost-Limburg
Genk, Belgium
AZ Maria Middelares Gent
Ghent, Belgium
Jan Yperman
Ieper, Belgium
AZ Groeninge
Kortrijk, Belgium
UZ Leuven
Leuven, Belgium
AZ Delta
Roeselare, Belgium
Noordwest Ziekenhuisgroep
Alkmaar, Netherlands
Amsterdam UMC
Amsterdam, Netherlands
OLVG
Amsterdam, Netherlands
Catharina Ziekenhuis
Eindhoven, Netherlands
Treant Zorggroep
Emmen, Netherlands
Zuyderland Ziekenhuis
Heerlen, Netherlands
Tergooi MC
Hilversum, Netherlands
St. Antonius Hospital
Nieuwegein, Netherlands
Hagaziekenhuis
The Hague, Netherlands
Elisabeth Tweesteden Ziekenhuis
Tilburg, Netherlands