Cardiotoxicity from Bruton tyrosine kinase inhibitors (BTKi) – an analysis of an administrative health claims database

Abstract Background: First generation Bruton tyrosine kinase inhibitors (BTKi) such as ibrutinib have been associated with cardiovascular toxicities. Newer generation BTKi (e.g.,acalabrutinib and zanabrutinib) have been associated with lower incidence of cardiotoxicity in clinical trials. Objective: Given paucity in real-world data on the overall cardiac risk factor profile, especially with the newer BTKi, our study evaluated the incidence of cardiotoxicity with various BTKi among a large, commercially insured population of patients. Methods: We performed a retrospective cohort analysis of all adults with a diagnosis of B-cell malignancy undergoing treatment with BTKi acalabrutinib and ibrutinib between January 2018 and June 2020 using Optum’s de-identified Clinformatics® Data Mart Database. We then identified patients who had pre-existing cardiac disease one year prior to starting BTKi, and six months after starting BTKi to keep drug exposure rates similar. New incidence of atrial fibrillation/flutter, hypertension, bleeding, ventricular tachycardia/fibrillation and sudden cardiac death were compared with standard Chi Square or Student t-test where appropriate. Multivariate logistic regression models were also estimated to evaluate for confounding. Results: A total of 1691 patients were included in the final analysis. 1595 (94%, median age 75 (19–90) years, 61% male gender) patients received ibrutinib, and 96 (6%, median age 73.5 (32–90) years, 62.5% male gender) patients received acalabrutinib. The median duration of drug exposure of ibrutinib was 238 (2-1084) days vs 150 (30–870) days for acalabrutinib. There was lower new incidence of atrial fibrillation/flutter (4.6%-vs-17%, p = 0.014), hypertension (6.3%-vs-25%, p = NS), ventricular tachycardia/fibrillation (0% vs 1.5%, p = NS) in the acalabrutinib group within six months of drug exposure compared to ibrutinib, of which only the lower incidence of atrial fibrillation/flutter was statistically significant. This was despite the finding of a higher prevalence of atrial fibrillation/flutter at baseline in patients receiving acalabrutinib. Conclusions: There was lower incidence of new atrial fibrillation/flutter with acalabrutinib when compared to ibrutinib in a real-world cohort of patients.