RecruitingPhase 4NCT04436978

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?


Sponsor

St. Antonius Hospital

Enrollment

2,000 participants

Start Date

Jan 11, 2023

Study Type

INTERVENTIONAL

Conditions

Summary

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.


Eligibility

Min Age: 18 Years

Inclusion Criteria3

  • 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 Criteria20

  • 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

Interventions

DRUG30-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.

DRUGGuideline-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)

AZ Delta

Roeselare, Belgium

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

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

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