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

Stroke Clinical Trial

— WOEST-3  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04436978
• Other study ID #: NL81102.100.22
• Secondary ID: 2022-001298-30
• Status: Recruiting
• Phase: Phase 4
• Start date: January 11, 2023
• Est. completion date: December 1, 2027

Study information

• Verified date: December 2023
• Source: St. Antonius Hospital
• Contact: Ashley Verburg, MD
• Phone: +31 (0)88 320 0925
• Email: as.verburg[@]antoniusziekenhuis.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: December 1, 2027
• Est. primary completion date: October 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Atrial Fibrillation
• Atrial Flutter
• Bleeding
• Coronary Artery Disease
• Coronary Disease
• Embolism
• Infarction
• Myocardial Infarction
• Myocardial Ischemia
• NSTEMI - Non-ST Segment Elevation MI
• ST Elevation Myocardial Infarction
• STEMI - ST Elevation Myocardial Infarction
• Stent Thrombosis
• Stroke
• Syndrome
• Thrombosis

Intervention

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.
• 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

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

Sponsors (2)

Lead Sponsor	Collaborator
St. Antonius Hospital	Daiichi Sankyo, Inc.

Countries where clinical trial is conducted

Belgium,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Quality of life as assessed by the EuroQol-5D-5L questionnaire	EuroQol-5D-5L questionnaire	6 weeks, 3 months, 6 months
Primary	Primary safety endpoint	Major or clinically relevant non-major bleeding as defined by the International Society of Thrombosis and Haemostasis	6 weeks
Primary	Primary efficacy endpoint	Composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis	6 weeks
Secondary	Bleeding complications	Major or clinically relevant non-major bleeding as defined by the International Society of Thrombosis and Haemostasis	6 months
Secondary	Thrombotic complications	Composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis	6 months
Secondary	Net clinical benefit	Composite of major bleeding, myocardial infarction, stroke, systemic embolism all-cause death and stent thrombosis	6 weeks, 3 months, 6 months
Secondary	Clinical symptom severity	CCS grade	6 weeks, 3 months, 6 months
Secondary	All-cause death	All-cause death as defined by ARC-2 and SCTI	6 weeks, 3 months, 6 months
Secondary	Myocardial infarction	Myocardial infarction as defined by the 4th Universal Definition of Myocardial Infarction	6 weeks, 3 months, 6 months
Secondary	Stroke	Stroke as defined by VARC-2 definitions	6 weeks, 3 months, 6 months
Secondary	Systemic embolism	Systemic embolism according to ENTRUST-AF PCI definition	6 weeks, 3 months, 6 months
Secondary	Stent thrombosis	Stent thrombosis as defined by ARC-2	6 weeks, 3 months, 6 months
Secondary	Major bleeding	Major bleeding as defined by BARC 3 or 5	6 weeks, 3 months, 6 months
Secondary	Clinically relevant non-major bleeding	CRNM as defined by BARC 2	6 weeks, 3 months, 6 months