Alessandro Mazzapicchi, Francesco Gallo, Luca Zanarelli, Francesco Filice, Michele Trichilo, Alfonso Ielasi, Maurizio Tespili, Macarena Grassi, Gennaro Carmine Semeraro, Giuseppe De Luca, Francesco Giannini
Background/Objectives: Atrial fibrillation and coronary artery disease frequently coexist in patients undergoing percutaneous left atrial appendage occlusion (LAAO), creating a complex therapeutic setting in which prevention of device-related thrombosis, cardioembolic events, and coronary ischemic complications must be balanced against a high or prohibitive bleeding risk. The optimal post-procedural antithrombotic regimen remains uncertain, particularly in patients with previous or recent percutaneous coronary intervention or acute coronary syndrome. Methods: This narrative review examines the rationale and current evidence supporting antithrombotic therapy after LAAO and integrates these data with contemporary strategies for abbreviated or de-escalated antiplatelet therapy after coronary intervention. Results: Device-related thrombosis occurs predominantly within the first 45-90 days after implantation, corresponding to the period of incomplete device endothelialisation, whereas thrombotic risk after coronary stenting or acute coronary syndrome is similarly greatest during the early phase and progressively declines thereafter. This temporal overlap supports an initially protective regimen followed by early treatment simplification whenever appropriate. We propose a pragmatic framework in which treatment intensity is determined by a global bleeding-thrombotic risk profile incorporating bleeding history, anaemia, comorbidities, frailty, coronary presentation, procedural complexity, and follow-up imaging. The approach includes predefined triggers for rapid de-escalation in the presence of relevant bleeding or haemoglobin decline and escalation when device-related thrombosis is detected. Conclusions: Current evidence remains heterogeneous and largely observational, the proposed algorithm should be considered a decision-support framework rather than a prescriptive pathway. Prospective randomised studies are needed to define the safest individualised regimen for patients with concomitant LAAO and coronary artery disease.