Bruton Tyrosine Kinase as Therapeutic Target in Cardiovascular Diseases-Executive Summary

Bruton tyrosine kinase (Btk) is an intracellular enzyme belonging to the Tec family tyrosine kinases. Initially identified for its role in B cell signaling, it has now emerged as a pivotal mediator in thrombosis and cardiovascular diseases (CVD). Beyond its established role in B cell malignancies, Btk is expressed in platelets, macrophages, neutrophils, and other innate immune cells, orchestrating platelet activation, atherothrombosis, venous thrombosis, immunothrombosis/thrombo-inflammation, and vascular inflammation. Patients with X-linked agammaglobulinemia (XLA), genetically lacking Btk, do not bleed, indicating that selective platelet Btk inhibition may provide a safe antithrombotic strategy. Indeed, highly selective Btk inhibitors (BTKi) show no or only minor bleeding in autoimmune disease trials, and rilzabrutinib, approved in 2025, reduces bleeding in patients with immune thrombocytopenia (ITP). This executive summary of a recent state-of-the-art review synthesizes current understanding of Btk's mechanistic contributions to thrombosis and CVD, evaluates the evolution of BTKi, and explores their therapeutic potential.