LAAO Versus NOAC in Patients with AF and PCI

Not Applicable

Recruiting

• Conditions: Atrial Fibrillation; Percutaneous Coronary Intervention
• Interventions: Device: The WATCHMAN/WATCHMAN FLX device; Drug: Rivaroxaban + Clopidogre; Drug: Aspirin + Clopidogrel

• Registration Number: NCT05353140
• Lead Sponsor: Xijing Hospital

Brief Summary

Atrial fibrillation (AF) coincides with coronary artery disease (CAD) shared common risk factors and pathophysiologic pathways. CAD affects approximately 25% of AF patient according to the trial Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM), while in the Global Registry of Acute Coronary Events (GRACE) atrial fibrillation affected about 9% of patients with CAD. It is reported that approximately 5-8% of the patients who underwent PCI had concomitated atrial fibrillation.

For AF patients who underwent PCI, both antiplatelet and antithrombotic medications are required for preventing stent thrombosis and ischemic stroke, leading to an increased risk of bleeding. Finding a safe and effective balance between the risk of ischaemic events and bleeding complications is challenged by the shared risk factors for either event such as advanced age, congestive heart failure, hypertension, diabetes, previous stroke, etc..

Previous pivotal trials have shown that in patients with atrial fibrillation and requiring antiplatelet treatment, a NOAC plus clopidogrel regimen was associated with a lower incidence of bleeding events as compared with a warfarin-based triple antithrombotic strategy. Therefore, the current expert opinions and consensus of North American Societies recommend a NOAC plus a P2Y12 inhibitor in patients with AF and PCI. However, the NOAC plus clopidogrel strategy still led to 16.8% of clinically significant bleeding (PIONEER AF-PCI). Consequently, the compliance of OAC/NOAC is commonly suboptimal among PCI patients who require an antithrombotic strategy for AF.

Percutaneous left atrial appendage occlusion (LAAO) is a non-pharmacological strategy for stroke prevention in patients with AF. Both randomized data and registries have confirmed it can be an alternative to oral anticoagulation in patients with nonvalvular AF. Current guidelines recommend LAAO for patients with NVAF who have contraindications or are unsuitable for long-term OAC.

Considering the unique high risk of AF patients with PCI, LAAO may be an attractive treatment option by obviating the need for combined oral anticoagulation and antiplatelet therapy. However, so far there is no data from neither randomized cohorts nor real-world registries showing if LAAO can be a safe and effective alternative strategy compared to VKA/NOAC for stroke prevention in AF patients who underwent PCI. The PROTECT AF and PREVAIL studies showed that the percutaneous LAAO was non-inferior to warfarin therapy, and the PRAGUE-17 trial showed non-inferior to direct oral anticoagulants, however, the small sample size of these trials limited further subgroup analyses of the PCI sub-population. In the NCDR registry, which is the largest cohort of LAAO up to now, 20.3% of the LAAO patients had a prior myocardial infarction. However, the proportion of stent implantation was not reported. Among previous trials, the proportion of patients with coronary artery disease ranged from 28.5% to 47.5%. The large number of AF patients with CAD warrant the optimal stroke prevention strategy to be assessed in this population.

The primary goal of the proposed study is to investigate if the non-inferiority would be met for the LAAO when compared to NOACs in NVAF patients with PCI in terms of a composite endpoint of any death, any stroke, any myocardial infarction, systemic embolism at 12 months. In addition, the powered key secondary will also have 80% of power to show superiority for the LAAO when compared to NOACs in terms of BARC type 2, 3, or 5 bleeding events at 36 months.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-04-22
• Study First Submitted QC: 2022-04-28
• Study First Posted: 2022-04-29
• Study Start: 2022-09-01
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-04
• Last Update Posted: 2025-03-07
• Primary Completion: 2028-09-20
• Study Completion: 2029-09-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1386

Inclusion Criteria

1. Successful PCI for unstable angina or CCS
2. Non-valvular atrial fibrillation
3. Concomitant at least one of the following conditions: congestive heart failure, hypertension, ≥65yrs, diabetes, previous stroke, TIA or thromboembolism
4. Eligible for long-term novel oral anti-coagulation (NOAC) therapy
5. Able to understand and provide informed consent and comply with all study procedures/medications

Exclusion Criteria

Patients who meet any of the following criteria will be disqualified from participation in the study:

Clinical exclusion criteria:

1. Under the age of 18
2. Unable to give informed consent or currently participating in another trial and not yet at its primary endpoint
3. Patient is a woman who is pregnant or nursing (a pregnancy test must be performed within 7 days prior to the index procedure in women of child-bearing potential according to local practice)
4. Concurrent medical condition with a life expectancy of less than 3 years
5. Haemodynamical unstable
6. Known contraindication to medications such as heparin, antiplatelet or anticoagulation drugs, or contrast
7. PCI for ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI), or experienced a peri-procedural myocardial infarction (MI) caused by PCI
8. Known contraindication to LAAO or LAAO is not required
9. Comorbidities other than atrial fibrillation that required long term use of anticoagulation (such as implanted a mechanical valve)
10. The patient had or is planning to have any cardiac (excluding the current PCI procedure) or non-cardiac interventional or surgical procedure within 30 days prior to or 60 days after the WATCHMAN device implant (e.g., cardioversion, ablation, cataract surgery)
11. Ongoing overt bleeding
12. Previous stroke/TIA within 30 days of enrolment
13. Symptomatic carotid artery disease
14. Severe renal insufficiency (CrCl≤30ml/min)

Imaging Exclusion Criteria:

1. Left atrial appendage (LAA) thrombus
2. High risk patent foramen ovale or atrial septal defect requiring invasive treatment
3. Anatomical unsuitable for LAAO
4. Rheumatic heart valve disease, mitral valve stenosis (valve area <1.5cm2)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Percutaneous left atrial appendage occlusion (LAAO)	Rivaroxaban + Clopidogre	Device: The WATCHMAN/WATCHMAN FLX device Drug: Rivaroxaban 15 mg QD + Clopidogrel 75mg QD for 45 days, followed by Aspirin 100mg QD + Clopidogrel 75mg QD for 10.5 months after LAAO
Novel oral anti-coagulation (NOAC)-based anti-thrombotic therapy	Rivaroxaban + Clopidogre	Drug: Rivaroxaban 15 mg QD + Clopidogrel 75mg QD for 12 months
Percutaneous left atrial appendage occlusion (LAAO)	The WATCHMAN/WATCHMAN FLX device	Device: The WATCHMAN/WATCHMAN FLX device Drug: Rivaroxaban 15 mg QD + Clopidogrel 75mg QD for 45 days, followed by Aspirin 100mg QD + Clopidogrel 75mg QD for 10.5 months after LAAO
Percutaneous left atrial appendage occlusion (LAAO)	Aspirin + Clopidogrel	Device: The WATCHMAN/WATCHMAN FLX device Drug: Rivaroxaban 15 mg QD + Clopidogrel 75mg QD for 45 days, followed by Aspirin 100mg QD + Clopidogrel 75mg QD for 10.5 months after LAAO

Primary Outcome Measures

Name	Time	Method
Major adverse cardiac and cerebrovascular events (MACCE)	12 months	MACCE define as a composite endpoint of any death, any stroke, any myocardial infarction (MI), and systemic embolism (SE).

Secondary Outcome Measures

Name	Time	Method
BARC type 2, 3 or 5 bleeding events	36 months	Powered Key secondary endpoint, Bleeding Academic Research Consortium (BARC) defined type 2, 3, 5 bleeding events

Trial Locations

Locations (1)

Ling Tao; 🇨🇳 Xi'an, Shannxi, China