Describe the biologic and mechanistic rationale for targeting factor XI/XIa in SPAF, and contrast FXI/XIa-directed strategies with current factor Xa-based DOAC therapy.

Differentiate mechanistic approaches to FXI pathway modulation—including zymogen-level inhibition with a monoclonal antibody and active-site inhibition with oral small-molecule FXIa inhibitors—and discuss how these differences may translate into distinct clinical profiles.

Evaluate the design, populations, and key endpoints of LIBREXIA-AF and LILAC-TIMI 76 in the context of prior FXI/XIa inhibitor trials (including OCEANIC-AF) to assess how these ongoing Phase 3 programs test the FXI/XIa hypothesis in AF.

Assess how potential efficacy and bleeding outcomes across FXI/XIa inhibitor programs could influence guideline recommendations; risk–benefit discussions; anticoagulant selection in diverse AF patient populations, including those unsuitable for current DOACs; current electrophysiology and AF clinic workflows; shared decision making in SPAF; and coordination across multidisciplinary care teams.