Bruton’s tyrosine kinase Inhibitors and Cardiotoxicity: More Than Just Atrial Fibrillation

Abstract

Purpose of Review The purpose of this review is to summarize the epidemiology, mechanisms, and management of cardiovascular complications of Bruton’s Tyrosine Kinase inhibitors (BTKIs). Recent Findings Ibrutinib increases the risk of atrial fibrillation, bleeding, and hypertension compared with non-BTKI therapies. The evidence to support an association between ibrutinib and other cardiovascular complications including ventricular tachyarrhythmias or cardiomyopathy is limited. Ibrutinib metabolism can be inhibited by some medications used to treat cardiovascular complications. The cardiovascular effects of more selective BTKIs, such as acalabrutinib, remain to be determined. Summary Future research should address the mechanisms underlying the cardiovascular complications of BTKIs and how best to manage them. The risks and benefits of more selective BTKIs as compared with ibrutinib require further evaluation.

A Novel Triple-Action Inhibitor Targeting B-Cell Receptor Signaling and BRD4 Demonstrates Preclinical Activity in Chronic Lymphocytic Leukemia

“…Individual drugs used to inhibit BTK, PI3K, and BET proteins each have unique side-effect profiles, and as such, additive side-effects from simultaneous inhibition of these pathways may occur. BTK inhibitors are associated with platelet effects and bleeding, as well as cardiovascular toxicities [ 79 ], and PI3K inhibitors carry the risk of inflammatory pneumonitis, liver toxicity, and inflammatory diarrhea [ 80 ]. BET inhibition is associated with anemia, thrombocytopenia, and neutropenia in advanced malignancies [ 81 , 82 ].…”

Real-World Persistence and Time to Next Treatment With Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Including Patients at High Risk for Atrial Fibrillation or Stroke

“…18 BTKis as a drug class have been associated with cardiovascular (CV) events such as atrial fibrillation (AF) and hypertension. [19][20][21] In clinical trials for ibrutinib, AF was observed in 4% of patients 8 ; long-term results from the RESONATE-2 trial revealed a 10% incidence of ibrutinibassociated AF after a median time of 29 months, although only 4% of events were grade 3 and symptoms resolved in 64% of patients after a median time of 3 days. 22 A real-world study of CLL patients treated at community-based practices and academic cancer centers in the US reported a similar rate of AF (10.2%, with 4.1% grade ≥3).…”

Reversible Systolic Heart Failure in a Patient on Ibrutinib Chemotherapy

“…Hypertension has been seen to occur after almost a year of Ibrutinib use, while the temporal correlation with atrial fibrillation and cardiomyopathy is not reported in the literature. Depletion of intracellular PI3/anaplastic lymphoma kinase and development of atrial fibrosis have been proposed to be the possible explanation for the occurrence of atrial fibrillation [ 10 ].…”