Overcoming NOAC-resistant left atrial appendage thrombus in atrial fibrillation: clinical gaps and therapeutic insights

Atrial fibrillation (AF) is the most common supraventricular arrhythmia and a major cause of stroke and systemic embolism. The left arial appendage (LAA) is the predominant site of thrombus formation in AF. According to current guidelines, oral anticoagulant (OAC) therapy is recommended in patients with elevated thromboembolic risk. Non-vitamin K antagonist oral anticoagulants (NOACs) are currently preferred over Vitamin K antagonists (VKAs) due to favorable safety profiles. Nevertheless, a subset of patients develop LAA thrombi despite optimal anticoagulant therapy, a clinical scenario not addressed by current guidelines. Recent retrospective studies, including our own cohort analysis, suggest, that modifying antithrombotic regimen may improve thrombus resolution in these cases. However, no prospective trials have yet defined the optimal strategy. This mini-review summarizes the available evidence, highlights the limitations of current practice, and proposes directions for future research in this underrecognized clinical dilemma.