Cardiovascular Safety of Bruton Tyrosine Kinase Inhibitors: From Ibrutinib to Next-Generation Agents

Bruton tyrosine kinase (BTK) plays a pivotal role in B-cell receptor signaling, making it a key therapeutic target in hematologic malignancies. Bruton tyrosine kinase inhibitors (BTKIs) have revolutionized the treatment landscape, improving survival outcomes in conditions such as chronic lymphocytic leukemia and mantle cell lymphoma. However, despite their clinical efficacy, BTKIs—particularly first-generation agents such as ibrutinib—are associated with significant cardiovascular toxicity, including atrial fibrillation, hypertension, bleeding, and, in rare cases, ventricular arrhythmias and heart failure. This narrative review explores the evolving landscape of BTKI-related cardiovascular toxicity, from first-generation drugs to next-generation agents that have improved safety profiles. We summarize current evidence on the incidence, mechanisms, and risk factors of BTKI-induced cardiovascular events and highlight potential predictive tools and mitigation strategies. Given the increasing use of these agents, a comprehensive understanding of their cardiovascular impact is essential for optimizing treatment selection and patient outcomes. Future research should focus on refining risk stratification models and developing cardioprotective strategies to ensure the long-term safety of BTKI therapy.