Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2024 Oct 1;9(10):922-926.
doi: 10.1001/jamacardio.2024.2335.

Low-Dose Direct Oral Anticoagulation vs Dual Antiplatelet Therapy After Left Atrial Appendage Occlusion: The ADALA Randomized Clinical Trial

Xavier Freixa  1 , Ignacio Cruz-González  2 , Pedro Cepas-Guillén  1 , Xavi Millán  3 , Pablo Antúnez-Muiños  1 , Eduardo Flores-Umanzor  1 , Lluís Asmarats  3 , Ander Regueiro  1 , Sergio López-Tejero  1 , Chi-Hion Pedro Li  3 , Laura Sanchis  1 , Josep Rodés-Cabau  1   4 , Dabit Arzamendi  3
Affiliations
Randomized Controlled Trial

Low-Dose Direct Oral Anticoagulation vs Dual Antiplatelet Therapy After Left Atrial Appendage Occlusion: The ADALA Randomized Clinical Trial

Xavier Freixa et al. JAMA Cardiol. .

Abstract

Importance: Optimal antithrombotic therapy after percutaneous left atrial appendage occlusion (LAAO) is not well established as no randomized evaluation has been performed to date.

Objective: To compare the efficacy and safety of low-dose direct oral anticoagulation (low-dose DOAC) vs dual antiplatelet therapy (DAPT) for 3 months after LAAO.

Design, setting, and participants: The ADALA (Low-Dose Direct Oral Anticoagulation vs Dual Antiplatelet Therapy After Left Atrial Appendage Occlusion) study was an investigator-initiated, multicenter, prospective, open-label, randomized clinical trial enrolling participants from June 12, 2019, to August 28, 2022 from 3 European sites. Patients who underwent successful LAAO were randomly assigned 1:1 to low-dose DOAC vs DAPT for 3 months after LAAO. The study was prematurely terminated when only 60% of the estimated sample size had been included due to lower recruitment rate than anticipated due to the COVID-19 pandemic.

Interventions: The low-dose DOAC group received apixaban, 2.5 mg every 12 hours, and the DAPT group received aspirin, 100 mg per day, plus clopidogrel, 75 mg per day, for the first 3 months after LAAO.

Main outcomes and measures: The primary end point was a composite of safety (major bleeding) and efficacy (thromboembolic events including stroke, systemic embolism, and device-related thrombosis [DRT]) within the first 3 months after successful LAAO. Secondary end points included individual components of the primary outcome and all-bleeding events.

Results: A total of 90 patients (mean [SD] age, 76.6 [8.1] years; 60 male [66.7%]; mean [SD] CHADS-VASc score, 4.0 [1.5]) were included in the analysis (44 and 46 patients in the low-dose DOAC and DAPT groups, respectively). A total of 53 patients (58.8%) presented with previous major bleeding events (60 gastrointestinal [66.7%] and 16 intracranial [17.8%]). At 3 months, low-dose DOAC was associated with a reduction of the primary end point compared with DAPT (2 [4.5%] vs 10 [21.7%]; hazard ratio, 0.19; 95% CI, 0.04-0.88; P = .02). Patients in the low-dose DOAC group exhibited a lower rate of DRT (0% vs 6 [8.7%]; P = .04) and tended to have a lower incidence of major bleeding events (2 [4.6%] vs 6 [13.0%]; P = .17), with no differences in thromboembolic events such as stroke and systemic embolism between groups (none in the overall population).

Conclusions and relevance: This was a small, randomized clinical trial comparing different antithrombotic strategies after LAAO. Results show that use of low-dose DOAC for 3 months after LAAO was associated with a better balance between efficacy and safety compared with DAPT. However, the results of the study should be interpreted with caution due to the limited sample size and will need to be confirmed in future larger randomized trials.

Trial registration: ClinicalTrials.gov Identifier: NCT05632445.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Freixa reported receiving grants from Bristol Myers Squibb and proctor fees from Abbott Medical and Lifetech during the conduct of the study. Dr Cruz-González reported receiving proctor fees from Abbott, Boston Scientific, and Lifetech outside the submitted work. Drs Millan, Asmarats, Regueiro, and Pedro Li reported receiving proctor fees from Abbott outside the submitted work. Dr Sanchis reported receiving speaker/proctor fees from Abbott, GE Healthcare, and Edwards Lifesciences outside the submitted work. Dr Rodés-Cabau reported receiving grants from Boston Scientific outside the submitted work. Dr Arzamendi reported receiving proctor fees from Abbott Medical and Boston Scientific. No other disclosures were reported.

Figures

Figure.
Figure.. Trial Flowchart
Enrollment and distribution of patients in the Apixaban vs Dual Antiplatelet Therapy Study After Left Atrial Appendage Occlusion (ADALA) study. ATT indicates antithrombic therapy; DAPT, dual antiplatelet therapy; DOAC, direct oral anticoagulation. aTrial stopped enrollment during COVID-19 crisis (from February 2020 to December 2020). bPatient discontinued intervention after no complicated pulmonary thromboembolism, starting full-dose DOAC.
See this image and copyright information in PMC

Comment in

References

    1. Mesnier J, Cepas-Guillén P, Freixa X, et al. Antithrombotic management after left atrial appendage closure: current evidence and future perspectives. Circ Cardiovasc Interv. 2023;16(5):e012812. doi: 10.1161/CIRCINTERVENTIONS.122.012812 - DOI - PubMed
    1. Della Rocca DG, Magnocavallo M, Di Biase L, et al. Half-dose direct oral anticoagulation vs standard antithrombotic therapy after left atrial appendage occlusion. JACC Cardiovasc Interv. 2021;14(21):2353-2364. doi: 10.1016/j.jcin.2021.07.031 - DOI - PubMed
    1. Duthoit G, Silvain J, Marijon E, et al. Reduced rivaroxaban dose vs dual antiplatelet therapy after left atrial appendage closure: ADRIFT a randomized pilot study. Circ Cardiovasc Interv. 2020;13(7):e008481. doi: 10.1161/CIRCINTERVENTIONS.119.008481 - DOI - PubMed
    1. Carvalho PEP, Gewehr DM, Miyawaki IA, et al. Network meta-analysis of initial antithrombotic regimens after left atrial appendage occlusion. J Am Coll Cardiol. 2023;82(18):1765-1773. doi: 10.1016/j.jacc.2023.08.010 - DOI - PubMed
    1. Flores-Umanzor EJ, Cepas-Guillen PL, Arzamendi D, Cruz-González I, Regueiro A, Freixa X. Rationale and design of a randomized clinical trial to compare two antithrombotic strategies after left atrial appendage occlusion: double antiplatelet therapy vs. apixaban (ADALA study). J Interv Card Electrophysiol. 2020;59(2):471-477. doi: 10.1007/s10840-020-00884-x - DOI - PubMed

Publication types

MeSH terms

Associated data