Weekly Journal Scan: rethinking factor XIa inhibition after acute coronary syndromes

This comment refers to ‘Milvexian with Antiplatelet Therapy after Acute Coronary Syndrome Event’, published in the New England Journal of Medicine; https://doi.org/10.1056/NEJMoa2608717. FⅪa inhibitors were developed around a very attractive -though not novel- therapeutic proposition: pathological thrombosis might be reduced while largely preserving physiological haemostasis, potentially dissociating efficacy from safety.2,3 LIBREXIA ACS tested this hypothesis in a contemporary ACS setting and prompts consideration of what this strategy of anticoagulation may offer to patients receiving intensive antiplatelet therapy. Moreover, most patients had undergone revascularization during the index hospitalization and were receiving guideline-directed medical therapy. The rationale for adding an oral anticoagulant in this intensively treated population rests on the persistence of high levels of thrombin generation and FⅪ despite effective platelet inhibition. This concept had found clinical support in the results of the ATLAS ACS 2–TIMI 51 trial, in which low-dose rivaroxaban added to antiplatelet therapy reduced cardiovascular death, MI, or stroke, at the cost of increased major and intracranial bleeding.4 FⅪa inhibition with milvexian offered the theoretical possibility of preserving this antithrombotic benefit with less interference with physiological haemostasis.