Apixaban vs Dual Antiplatet Therapy Study After Left Atrial Appendage Occlosure (ADALA)
Status:
Completed
Trial end date:
2022-10-30
Target enrollment:
Participant gender:
Summary
Objective: To demonstrate superiority of a strategy of anticoagulation with apixaban
5mg/2.5mg bid as compared with the current standard of care (dual antiplatelet therapy) after
occlusion of the left atrial appendage (LAAC) in patients with atrial fibrillation (AF).
Rationale: Data on antithrombotic therapy after LAAC are scarce and no randomized evaluation
has been performed to demonstrate what is the best antithrombotic strategy. LAAO in patients
without contraindication to chronic anticoagulants (PROTECT-AF regimen) is a 6-week period of
anticoagulation with warfarin associated with aspirin, followed by once daily clopidogrel (75
mg) and aspirin (81-325 mg) until the 6 months visit, then aspirin alone is continued
indefinitely, as tested in the pivotal trials. LAAO is also being used as an alternative to
warfarin anticoagulation when patients have a contraindication or are unsuitable to warfarin.
These patients usually receive a regimen of daily clopidogrel and aspirin (DAPT) for 3
months. Some may receive a shorter duration of DAPT or even only single antiplatelet therapy
(SAPT) in case of excess bleeding risk. This antiplatelet regimen has never been compared
with any anticoagulation regimen after LAAC. The Investigators propose to evaluate a unique
antithrombotic strategy after LAAC for atrial fibrillation, whatever the indication of LAAC,
including patients not suitable for long term warfarin anticoagulation. This strategy uses
apixaban 5mg (with dose adjustment when necessary) which will be compared to the standard of
care based on antiplatelet therapy and which may vary according to the risk profile of the
patient. Apixaban, has demonstrated a mortality benefit associated with significant
reductions in stroke, systemic embolism and major bleeding versus VKA. In addition, apixaban
is the only NOAC which has demonstrated superiority over aspirin alone, in AF patients not
suitable for chronic warfarin anticoagulation, to prevent cardio-embolic events with a safety
profile similar to aspirin.The Investigators therefore formulate the hypothesis that apixaban
is superior to standard of care (APT) to prevent cardiovascular events and bleeding
complications after LAAO.
Population: Inclusion criteria: AF patients who have undergone a successful LAAO procedure.
Exclusion criteria include any indication for triple antithrombotic treatment, mechanical
heart valve, use of prasugrel or ticagrelor, serious renal failure defined as a creatinine
clearance <15mL/min, contraindication to any form of anticoagulation or antiplatelet therapy.
Randomization will occur always before hospital discharge as soon as the patient is stable or
stabilized after the procedure.
Randomization: Apixaban vs. APT, both for 3 months. Groups: 1/Apixaban 5mg or 2.5mg bid (if
dose adjustment needed). 2/ DAPT using low-dose ASA (75-100mg) and clopidogrel (75mg); or in
patients with a history of intracranial hemorrhage (ICH) SAPT (aspirin or clopidogrel) will
be used instead of DAPT from the time of randomization.
Follow-up: 12 months from randomization Primary endpoint: combined enpoint of death, MI,
stroke, thromboembolic complications, major or significant bleeding at 3 months follow-up.
Sample size: In order to find a 16% difference in the event rates among the two treatment
strategies, using a logrank test with a 5% two-sided significance level, we will need 76
patients in each group (152 in total). However, to compensate patient drop out, a total of
160 patients will be included in the study.
Recruitment : 24 months Centers: 3 centers in Spain.