Bleeding, Left Atrial Appendage Closure, Stroke, Thrombosis, TIA
Conditions
Keywords
Left Atrial Appendage Closure, Anticoagulation therapy, Antiplatelet therapy
Brief summary
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
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.
Interventions
DRUGRivaroxaban, dabigatran, apixaban, or edoxaban
Duration of treatment: 60 days
DRUGClopidogrel -75 mg/day
Duration of treatment: 60 days
DRUGLow dose aspirin -80 to 125 mg/day-
Duration of treatment: 60 days
Sponsors
Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Device thrombosis (efficacy outcome) | 60 days after LAAC | Evaluated by TEE |
| Combined outcome of all-cause mortality, bleeding, stroke, or Device thrombosis (Safety outcome) | 60 days after LAAC | Clinically evaluated and diagnosed by the center investigators and determining a treatment change. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Device thrombosis | 12 months after LAAC | Evaluated by TEE or computed tomography |
| Ischemic events | 60 days, 12-month, 2-year, 3-year, 4-year and 5-year follow-up | Stroke, TIA |
| 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 | 60 days and 12-month, 2-year, 3-year, 4-year and 5-year follow-up | All cause mortality |
Countries
Canada
Outcome results
None listed