[Cardiovascular adverse effects of Bruton tyrosine kinase inhibitors: Pathophysiological mechanisms, screening, and management]

Abstract

The covalent Bruton tyrosine kinase inhibitors (iBTKs) have profoundly transformed the management of B-cell lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL). These targeted therapies, with ibrutinib as the pioneer, have paved the way for significant improvement in the prognosis of many patients. With second-generation iBTKs such as acalabrutinib and zanubrutinib, the therapeutic landscape has expanded, offering potential new options for patients with CLL. This review focuses on the cardiovascular adverse effects associated with these treatments. It delves into the underlying pathophysiological mechanisms of these effects, highlighting the complex interactions between these molecules and the cardiovascular system. Additionally, it examines the frequency of adverse effects according to the type of iBTK, drawing on data from clinical trials and real-world clinical practice. Finally, the importance of close cardio-oncological monitoring is emphasized, with essential collaboration between hematologists and cardiologists. Strategies for screening and managing cardiovascular adverse effects are also discussed, emphasizing the need for a proactive approach in managing these complications. Experts propose a pragmatic follow-up of these patients, through a central illustration and a figure adapted from European cardio-oncology guidelines, to simplify hematologists' practice.

Keywords: AF; Bruton tyrosine kinase inhibitors; Cardiovasculaire; Cardiovascular; Chronic lymphocytic leukemia; Fibrillation atriale; HTN; Hypertension artérielle; Inhibiteurs de la Bruton tyrosine kinase; Leucémie lymphoïde chronique; Toxicity; Toxicité.