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

Phase 4

Recruiting

• Conditions: Atrial Fibrillation; Atrial Flutter; Stent Thrombosis; Acute Coronary Syndrome; Embolism; Myocardial Infarction; NSTEMI - Non-ST Segment Elevation MI; STEMI - ST Elevation Myocardial Infarction; Bleeding; Stroke
• Interventions: Drug: 30-day DAPT; Drug: Guideline-directed therapy

• Registration Number: NCT04436978
• Lead Sponsor: St. Antonius Hospital

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-06-16
• Study First Submitted QC: 2020-06-16
• Study First Posted: 2020-06-18
• Study Start: 2023-01-11
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-14
• Last Update Posted: 2023-12-15
• Primary Completion: 2027-10-01
• Study Completion: 2027-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 2000

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
First month DAPT	30-day 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.
Guideline-directed therapy	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.

Primary Outcome Measures

Name	Time	Method
Primary efficacy endpoint	6 weeks	Composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis
Primary safety endpoint	6 weeks	Major or clinically relevant non-major bleeding as defined by the International Society of Thrombosis and Haemostasis

Secondary Outcome Measures

Name	Time	Method
Clinical symptom severity	6 weeks, 3 months, 6 months	CCS grade
Bleeding complications	6 months	Major or clinically relevant non-major bleeding as defined by the International Society of Thrombosis and Haemostasis
Thrombotic complications	6 months	Composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis
Net clinical benefit	6 weeks, 3 months, 6 months	Composite of major bleeding, myocardial infarction, stroke, systemic embolism all-cause death and stent thrombosis
All-cause death	6 weeks, 3 months, 6 months	All-cause death as defined by ARC-2 and SCTI
Myocardial infarction	6 weeks, 3 months, 6 months	Myocardial infarction as defined by the 4th Universal Definition of Myocardial Infarction
Stroke	6 weeks, 3 months, 6 months	Stroke as defined by VARC-2 definitions
Systemic embolism	6 weeks, 3 months, 6 months	Systemic embolism according to ENTRUST-AF PCI definition
Stent thrombosis	6 weeks, 3 months, 6 months	Stent thrombosis as defined by ARC-2
Major bleeding	6 weeks, 3 months, 6 months	Major bleeding as defined by BARC 3 or 5
Clinically relevant non-major bleeding	6 weeks, 3 months, 6 months	CRNM as defined by BARC 2

Trial Locations

Locations (20)

Catharina Ziekenhuis; 🇳🇱 Eindhoven, Netherlands

Imelda Ziekenhuis; 🇧🇪 Bonheiden, Belgium

Hagaziekenhuis; 🇳🇱 Den Haag, Netherlands

Ziekenhuis Oost-Limburg; 🇧🇪 Genk, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium

Noordwest Ziekenhuisgroep; 🇳🇱 Alkmaar, Netherlands

AZ Maria Middelares Gent; 🇧🇪 Gent, Belgium

AZ Groeninge; 🇧🇪 Kortrijk, Belgium

ASZ Aalst; 🇧🇪 Aalst, Belgium

UZ Antwerpen; 🇧🇪 Antwerpen, Belgium

Jan Yperman; 🇧🇪 Ieper, Belgium

AZ Delta; 🇧🇪 Roeselare, Belgium

Amsterdam UMC; 🇳🇱 Amsterdam, Netherlands

OLVG; 🇳🇱 Amsterdam, Netherlands

Treant Zorggroep; 🇳🇱 Emmen, Netherlands

Zuyderland Ziekenhuis; 🇳🇱 Heerlen, Netherlands

UZ Brussel; 🇧🇪 Brussel, Belgium

Tergooi MC; 🇳🇱 Hilversum, Netherlands

St. Antonius Hospital; 🇳🇱 Nieuwegein, Netherlands

Elisabeth Tweesteden Ziekenhuis; 🇳🇱 Tilburg, Netherlands