Short-Term Anticoagulation Versus Antiplatelet Therapy for Preventing Device Thrombosis Following Left Atrial Appendage Closure

Study Overview
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Brief Summary
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The objective of the study is to compare short-term (8 weeks) anticoagulation therapy (DOAC) vs. antiplatelet therapy for the prevention of device thrombosis following transcatheter LAAC.

Detailed Description
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Transcatheter left atrial appendage closure (LAAC) has emerged as an alternative to anticoagulation for preventing thromboembolic events in patients with atrial fibrillation. Whereas most complications associated with LAAC have decreased over time, the occurrence of device thrombosis remains a concern, with an incidence of 1 to 17%. Antithrombotic therapy for preventing device thrombosis following LAAC has evolved empirically, with antiplatelet therapy being the most commonly prescribed treatment. However, the rates of device thrombosis post-LAAC remain relatively high and have not decreased over time despite of increasing operator/center experience and the arrival of newer generation devices. This is of particular concern if we consider that LAAC is a preventive treatment. Experimental and mechanistic studies have suggested enhanced thrombin generation (and not platelet activation) within the days-weeks following the procedure as the most important mechanism involved in device thrombosis and appropriate short-term anticoagulation therapy with DOAC should translate into a significant reduction in the rate of device thrombosis post-LAAC. Therefore, the objective of the study is to compare short-term (60 days) anticoagulation therapy (DOAC) vs. antiplatelet therapy for the prevention of device thrombosis following transcatheter LAAC. It is estimated that 350 patients will take part in the study. Update: A blinded interim analysis was performed with the analysis of clinical and TEE (central echo core lab) data from the initial 155 patients included in the study. Based on the results of the interim analysis, and considering the total number of events and the high rate (20%) of patients with either early cessation of the allocated treatment (before the 60-day TEE examination) or missing TEE at 60 days, it was decided to increase the sample size by 160 patients up to a total of 510 patients. This would ensure to include at least 350 patients with a TEE examination performed while receiving the allocated antithrombotic treatment.

Official Title
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Short-Term Anticoagulation Versus Antiplatelet Therapy for Preventing Device Thrombosis Following Left Atrial Appendage Closure. The ANDES Trial

Conditions
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Thrombosis, Left Atrial Appendage Closure, Stroke, TIA, Bleeding

Intervention / Treatment
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* Drug: Rivaroxaban, dabigatran, apixaban, or edoxaban
* Drug: Clopidogrel -75 mg/day
* Drug: Low dose aspirin -80 to 125 mg/day-


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Successful transcatheter LAAC with any approved device Age≥18 years old Exclusion Criteria: Absolute contraindications for anticoagulation therapy Absolute contraindications for antiplatelet therapy End-stage renal disease (CrCl <15 ml/min) Recent percutaneous revascularization with drug-eluting stents requiring dual antiplatelet therapy Prior intracranial hemorrhage Contraindications for TEE Severe pericardial effusion within the first 24 hrs following LAAC Major/life-threatening bleeding event within the month prior to LAAC Multiple bleeding events (minor or major) within the month prior to LAAC Major/life-threatening bleeding within the first 24 hrs following LAAC

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Anticoagulation therapy<br>Direct oral anticoagulants (rivaroxaban, dabigatran, apixaban, or edoxaban; with dosage according to guideline recommendations) for 60 days. | Drug: Rivaroxaban, dabigatran, apixaban, or edoxaban<br>* Duration of treatment: 60 days<br>|
| Active Comparator: Antiplatelet therapy<br>Dual antiplatelet therapy with clopidogrel -75 mg/day- and low dose aspirin -80 to 125 mg/day for 60 days. | Drug: Clopidogrel -75 mg/day<br>* Duration of treatment: 60 days<br>Drug: Low dose aspirin -80 to 125 mg/day-<br>* Duration of treatment: 60 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device thrombosis (efficacy outcome) | Evaluated by TEE | 60 days after LAAC | 
| Combined outcome of all-cause mortality, bleeding, stroke, or Device thrombosis (Safety outcome) | Clinically evaluated and diagnosed by the center investigators and determining a treatment change. | 60 days after LAAC | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device thrombosis | Evaluated by TEE or computed tomography | 12 months after LAAC | 
| Ischemic events | Stroke, TIA | 60 days, 12-month, 2-year, 3-year, 4-year and 5-year follow-up | 
| Bleeding events |  | 60 days and 12-month, 2-year, 3-year, 4-year and 5-year follow-up | 
| Major or Life-threatening bleeding events |  | 60 days and 12-month, 2-year, 3-year, 4-year and 5-year follow-up | 
| Mortality | All cause mortality | 60 days and 12-month, 2-year, 3-year, 4-year and 5-year follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Left Atrial Appendage Closure, Anticoagulation therapy, Antiplatelet therapy