Clinical trial NCT04436978: What is the Optimal Antithrombotic Strategy in Patients With Atrial Fibrillation Undergoing PCI?
Official title: What is the Optimal Antithrombotic Strategy in Patients With Atrial Fibrillation Having Acute Coronary Syndrome or Undergoing Percutaneous Coronary Intervention?
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: 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
Keywords: 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
Lead sponsor: St. Antonius Hospital
Sponsor class: OTHER
Collaborators: name: Daiichi Sankyo
First posted: 2020-06-18
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

* 30 days DAPT (asprin + P2Y12 inhibitor), followed by guideline-directed therapy (edoxaban + P2Y12 inhibitor)
* Standard guideline-directed therapy (edoxaban + P2Y12 inhibitor, aspirin limited to in-hospital use or up to 30 days in selected high-risk patients)
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Primary safety endpoint
timeFrame: 6 weeks
measure: Primary efficacy endpoint
timeFrame: 6 weeks
Secondary outcomes:
measure: Bleeding complications
timeFrame: 6 months
measure: Thrombotic complications
timeFrame: 6 months
measure: Net clinical benefit
timeFrame: 6 weeks, 3 months, 6 months
measure: Clinical symptom severity
timeFrame: 6 weeks, 3 months, 6 months
measure: All-cause death
timeFrame: 6 weeks, 3 months, 6 months
measure: Myocardial infarction
timeFrame: 6 weeks, 3 months, 6 months
measure: Stroke
timeFrame: 6 weeks, 3 months, 6 months
measure: Systemic embolism
timeFrame: 6 weeks, 3 months, 6 months
measure: Stent thrombosis
timeFrame: 6 weeks, 3 months, 6 months
measure: Major bleeding
timeFrame: 6 weeks, 3 months, 6 months
measure: Clinically relevant non-major bleeding
timeFrame: 6 weeks, 3 months, 6 months
Other outcomes:
measure: Quality of life as assessed by the EuroQol-5D-5L questionnaire
timeFrame: 6 weeks, 3 months, 6 months
Locations:
city: Aalst
country: Belgium
facility: ASZ Aalst
city: Antwerpen
country: Belgium
facility: UZ Antwerpen
city: Bonheiden
country: Belgium
facility: Imelda Ziekenhuis
city: Brussel
country: Belgium
facility: UZ Brussel
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
city: Gent
country: Belgium
facility: AZ Maria Middelares Gent
city: Ieper
country: Belgium
facility: Jan Yperman
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven
city: Roeselare
country: Belgium
facility: AZ Delta
city: Alkmaar
country: Netherlands
facility: Noordwest Ziekenhuisgroep
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Amsterdam
country: Netherlands
facility: OLVG
city: Den Haag
country: Netherlands
facility: Hagaziekenhuis
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Emmen
country: Netherlands
facility: Treant Zorggroep
city: Heerlen
country: Netherlands
facility: Zuyderland Ziekenhuis
city: Hilversum
country: Netherlands
facility: Tergooi MC
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
city: Tilburg
country: Netherlands
facility: Elisabeth Tweesteden Ziekenhuis
Study officials:
affiliation: St. Antonius Hospital
name: Jurriën M ten Berg, Prof, MD
role: PRINCIPAL_INVESTIGATOR
References: