Evaluation of 2 doses of rivaroxaban (10 and 15 mg) compared to dual anti platelet therapy (aspirin+clopidogrel) after left atrial appendage closure. The patients will be assessed at 10 and 90 days: central laboratory hemostasis analysis and clinical events assessment.
Data on antithrombotic therapy after Left Atrial Appendage Closure (LAAC) are scarce and no randomized evaluation has been performed to demonstrate what is the best antithrombotic strategy following LAAC. LAAC is classically associated with a 6-week period of anticoagulation with warfarin + aspirin followed by once daily clopidogrel (75 mg) + aspirin (81-325 mg) until the 6 months visit, then aspirin alone is continued indefinitely, as tested in patients without contraindication for anticoagulation in the pivotal Watchman trials. LAAC is mostly used in Europe as an alternative to warfarin anticoagulation when patients have a contraindication to or are unsuitable for warfarin anticoagulation. The classic regimen is not applicable and believed to be too risky in such frail patients. These patients usually receive a regimen of daily clopidogrel + aspirin followed by single antiplatelet therapy (most frequently used treatment). Some patients receive oral anticoagulation without aspirin, including NOAC anticoagulation. Rivaroxaban is a tempting strategy for anticoagulation following LAAC in atrial fibrillation (AF) patients. The dose needs first to be carefully evaluated the trial propose a dose ranging study in patients who have undergone successful LAAC.
The study will evaluate two different Rivaroxaban regimen (10 or 15 mg a day) in comparison to dual antiplatelet therapy (DAPT) (aspirin+clopidogrel : control arm representing standard of care) after successful LAAC. The aim is to investigate whether rivaroxaban could provide correct anticoagulation levels and adequately suppress coagulation activation after LAAC.
The patient will be enrolled after left atrial appendage closure before discharge. The randomization is 1/1/1 between the 3 groups : rivaroxaban 10mg a day, rivaroxaban 15 mg a day and aspirin 75mg + clopidogrel 75 mg a day. At 10 and 90 days, the patients will be sampled for biological assessment : Prothrombin fragments 1+2, Factor Xa inhibitory activity, Russel Viper venom enzyme assay, thrombin anti-thrombin (TAT) complex, D-Dimers, Prothrombin time (Neoplastin) and plasma von Willebrand factor (vWf) Ag level
After 90 days, the patient will end his/her participation in the trial. Clinical endpoints (death, MI, Stroke, TIA, systemic embolism, extracranial major bleeding or clinically relevant non major bleeding) at 90 days will be assessed by a clinical endpoint committee. Central echographic laboratory will review all 90 days transesophageal echocardiography (TEE) to detect the presence of thrombus or peri-device leak.
The study is open-label. Central laboratory, clinical endpoint committee and echographic core laboratory is blinded to randomization arm.
- Rivaroxaban 10 mg qd Drug
Intervention Desc: 10mg qd ARM 1: Kind: Experimental Label: 1: Rivaroxaban 10 mg qd Description: Rivaroxaban 10 mg, 1 tablet a day, from randomization to Day 90 should be taken between 8 and 10 AM
- Rivaroxaban 15 mg qd Drug
Intervention Desc: 15mg qd ARM 1: Kind: Experimental Label: 2: Rivaroxaban 15 mg qd Description: Rivaroxaban 15 mg, 1 tablet a day, from randomization to Day 90 should be taken between 8 and 10 AM
- DAPT Drug
Intervention Desc: Aspirin 75 mg qd + Clopidogrel 75 mg qd ARM 1: Kind: Experimental Label: 3: DAPT Description: Aspirin 75 mg, 1 a day Clopidogrel 75 mg, 1 tablet a day from randomization to Day 90 should be taken between 8 and 10 AM
|Type||Measure||Time Frame||Safety Issue|
|Primary||Measure of prothrombin fragment 1 + 2||at Day 10|
|Secondary||Factor Xa inhibitory activity||at Day 10|
|Secondary||Russel Viper venom enzyme assay||at Day 90|
|Secondary||TAT complex||at Day 10|
|Secondary||D-Dimers||at Day 10|
|Secondary||Prothrombin time (Neoplastin)||at Day 10|
|Secondary||Plasma vWf Ag level||at Day 10|
|Secondary||Haemorrhagic stroke and bleeding will be safety outcomes TEE with central core lab reading: presence of thrombus, peri-device leak||at Day 90|
|Secondary||Composite clinical endpoint combining all clinical outcomes : Death, MI, stroke, TIA,||at Day 90|
|Secondary||Death (any cause)||at Day 90|
|Secondary||Myocardial infarction (MI)||at Day 90|
|Secondary||Stroke (ischaemic stroke, haemorrhagic stroke)||at Day 90|
|Secondary||Transient Ischemic Attack (TIA)||at Day 90|
|Secondary||Systemic embolism||at Day 90|
|Secondary||Extracranial major bleeding or clinically relevant non major bleeding (ISTH definition)||at Day 90|