Low-dose NOAC Versus GDMT After LAAO

Official title

Low-dose Rivaroxaban Monotherapy Versus Guideline Determined Medication Therapy After Left Atrial Appendage Occlusion: a Randomized, Open-label, Multicentre, Superiority Trial

Overview

The increased risk of Atrial fibrillation (AF) regarding thromboembolic stroke is predominantly due to the formation and embolization of clots from within the left atrial appendage (LAA). Percutaneous left atrial appendage occlusion (LAAO) is a nonpharmacological strategy for stroke prevention in patients with AF. Data from randomized trials, including PROTECT-AF, PREVAIL, and Prague-17, have suggested that LAAO has comparable efficacy to warfarin or NOACs. Considering these results, LAAO was recommended by the American College of Cardiology (ACC) and European Society of Cardiology (ESC) guidelines as a non-pharmacological stroke prevention strategy for patients with NVAF who have contraindications or are unsuitable for OAC. The PROTECT-AF and PREVAIL trials stipulated the use of standardized antithrombotic medications which were designed to minimize the risk of stroke, systemic embolism, or device-related thrombosis. This antithrombotic strategy was subsequently endorsed by the guidelines, briefly, patients with LAAO were discharged on warfarin and aspirin for 45 days post-LAAO, if there was no leak or a leak ≤5 mm under transesophageal echocardiography (TEE) at 45-day follow-up, antithrombotic strategies shall switch to dual antiplatelet therapy (DAPT) until 6 months post-LAAO, and then aspirin thereafter. Although LAAO was recommended by medical societies, previous patient-level meta-analyses have implied that compared with oral anticoagulation, LAAO had significantly more ischemic strokes, suggesting the inability of LAAO to prevent an ischemic stroke from sources beyond LAA. Will a combined strategy of LAAO and OAC further reduce the risk of stroke? The investigators hypothesized that a long-term low dose-Rivaroxaban (10mg daily) post-LAAO might be a potent supplement to the residue risk of ischemic stroke.

Interventions

• Drug Rivaroxaban 15mg
  QD
• Drug Aspirin 100mg
  QD
• Drug Clopidogrel 75mg
  QD
• Drug Rivaroxaban 10mg
  QD
• Drug Rivaroxaban 2.5mg
  B.I.D

Primary outcome measures

• Rate of the composite endpoint of any death, any stroke, systemic embolism, and The Bleeding Academic Research Consortium (BARC)-defined 3 or 5 bleeding events [Time frame: 24 months post randomization]

Secondary outcome measures (12)

• Rate of the composite endpoint of any death, any stroke, systemic embolism, and BARC defined 3 or 5 bleeding events [Time frame: 45 days, 6, 12 months (Time-to-event)]
• Rate of the composite endpoint of any death, any stroke, systemic embolism [Time frame: 45 days, 6, 12, 24 months (Time-to-event)]
• Rate of the BARC type 3 or 5 bleeding events [Time frame: 45 days, 6, 12, 24 months (Time-to-event)]
• Rate of the composite endpoint of any death, any stroke, systemic embolism, myocardial infarction (MI) [Time frame: 45 days, 6, 12, 24 months (Time-to-event)]
• Rate of any death [Time frame: 45 days, 6, 12, 24 months (Time-to-event)]
• Rate of any stroke [Time frame: 45 days, 6, 12, 24 months (Time-to-event)]
• Rate of systemic embolism [Time frame: 45 days, 6, 12, 24 months (Time-to-event)]
• Rate of myocardial infarction (MI) [Time frame: 45 days, 6, 12, 24 months (Time-to-event)]
• Rate of BARC type 2, 3 or 5 bleeding events [Time frame: 45 days, 6, 12, 24 months (Time-to-event)]
• Rate of BARC type 2 bleeding events [Time frame: 45 days, 6, 12, 24 months (Time-to-event)]
• Rate of BARC type 3 bleeding events [Time frame: 45 days, 6, 12, 24 months (Time-to-event)]
• Rate of BARC type 5 bleeding events [Time frame: 45 days, 6, 12, 24 months (Time-to-event)]

Eligibility criteria

Inclusion criteria

• Non-valvular atrial fibrillation (NVAF) patients with successful left atrial appendage occlusion (LAAO)
• Eligible for guideline-directed anti-thrombotic therapy
• Able to understand and provide informed consent and comply with all study medications

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 two years
• Haemodynamical unstable
• Known contraindication to medications such as heparin, antiplatelet or anticoagulation drugs, or contrast
• Peridevice leak > 5mm as assessed immediately after LAAO or any other procedure-related complications
• Comorbidities other than atrial fibrillation that required long term use of anticoagulation (such as implanted mechanical valve)
• Percutaneous coronary intervention (PCI) within 1 year.
• The patient had or is planning to have any cardiac or non-cardiac interventional or surgical procedure within 30 days prior to or 60 days after the WATCHMAN device implant (e.g., PCI, cardioversion, cardiac surgery)
• Ongoing overt bleeding
• Previous stroke/TIA within 30 days of enrolment
• Symptomatic carotid artery disease
• Severe renal insufficiency (CrCl≤30ml/min/1.73m2)

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

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Ling Tao — Xi'an

Identifiers

NCT: NCT05960721 · RECORD-III

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗