LAAO Versus NOAC in Patients with AF and PCI

Official title

Left Atrial Appendage Occlusion Versus Novel Oral Anti-coagulation in Patients with Atrial Fibrillation and Percutaneous Coronary Intervention: a Randomized, Multicentre, Open-label, Non-inferiority Trial

Overview

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.

Interventions

• Device The WATCHMAN/WATCHMAN FLX device
  Watchman device was an umbrella-shaped, self-expanding, nitinol structure with a porous partial polyethylene terephthalate membrane (160 um mesh) and 10 struts. The membrane portion of the structure faces into the body of the left atrial to block embolization of thrombus and provide scaffolding on which endothelialization can occur. The On July 21st, 2020, the FDA approved the next generation LAAO device, named Watchman FLX. This newiteration of the Watchman LAAO platform offers full capability
• Drug Rivaroxaban + Clopidogre
  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. In the present study, Rivaroxaban + Clopidogre are required for 45 days in LAAO
• Drug Aspirin + Clopidogrel
  Aspirin + Clopidogrel are required from 46 days to 12 months after LAAO.

Primary outcome measures

• Major adverse cardiac and cerebrovascular events (MACCE) [Time frame: 12 months]

Secondary outcome measures (1)

• BARC type 2, 3 or 5 bleeding events [Time frame: 36 months]

Eligibility criteria

Inclusion criteria

• Successful PCI for unstable angina or CCS
• Non-valvular atrial fibrillation
• Concomitant at least one of the following conditions: congestive heart failure, hypertension, ≥65yrs, diabetes, previous stroke, TIA or thromboembolism
• Eligible for long-term novel oral anti-coagulation (NOAC) therapy
• 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:

• Under the age of 18
• Unable to give informed consent or currently participating in another trial and not yet at its primary endpoint
• 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)
• Concurrent medical condition with a life expectancy of less than 3 years
• Haemodynamical unstable
• Known contraindication to medications such as heparin, antiplatelet or anticoagulation drugs, or contrast
• 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
• Known contraindication to LAAO or LAAO is not required
• Comorbidities other than atrial fibrillation that required long term use of anticoagulation (such as implanted a mechanical valve)
• 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)
• Ongoing overt bleeding
• Previous stroke/TIA within 30 days of enrolment
• Symptomatic carotid artery disease
• Severe renal insufficiency (CrCl≤30ml/min)

Imaging Exclusion Criteria:

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

China · 1 center

• Ling Tao — Xi'an

Identifiers

NCT: NCT05353140 · RECORD II

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗