Cardiovascular Toxicity of BTK Inhibitors: A Patient-Centered Framework for Risk Stratification and Management

Bruton tyrosine kinase inhibitors have transformed the management of chronic lymphocytic leukemia and other B-cell malignancies, but their clinical use is increasingly influenced by cardiovascular safety. In contemporary practice, patients receiving these therapies are typically older and characterized by a high burden of comorbidities, including cardiovascular disease, metabolic disorders, and renal impairment. In this setting, cardiovascular complications should not be interpreted as isolated adverse events, but rather as clinical expressions of underlying patient vulnerability and frailty. Atrial fibrillation and arterial hypertension represent the most frequent complications, while heart failure, ventricular arrhythmias, and bleeding, although less common, may carry significant prognostic implications. Importantly, these events often arise from the interaction between drug exposure and pre-existing comorbidities, and may lead to treatment interruption, dose reduction, or discontinuation, ultimately compromising the long-term benefit of otherwise highly effective therapies. This review provides a comprehensive overview of the clinical burden, mechanisms, and management of cardiovascular complications associated with these agents, and proposes a practical, patient-centered framework to guide clinical decision-making. A structured approach based on risk assessment, early detection, and proactive management is essential to prevent complications, optimize treatment continuity, and preserve the long-term benefit of therapy in a complex and vulnerable population.