Association between ibrutinib treatment and hypertension

Abstract

BackgroundIbrutinib is a tyrosine kinase inhibitor most commonly associated with atrial fibrillation. However, additional cardiotoxicities have been identified, including accelerated hypertension. The incidence and risk factors of new or worsening hypertension following ibrutinib treatment are not as well known.MethodsWe conducted a retrospective study of 144 patients diagnosed with B cell malignancies treated with ibrutinib (n=93) versus conventional chemoimmunotherapy (n=51) and evaluated their effects on blood pressure at 1, 2, 3 and 6 months after treatment initiation. Descriptive statistics were used to compare baseline characteristics for each treatment group. Fisher’s exact test was used to identify covariates significantly associated with the development of hypertension. Repeated measures analyses were conducted to analyse longitudinal blood pressure changes.ResultsBoth treatments had similar prevalence of baseline hypertension at 63.4% and 66.7%, respectively. There were no differences between treatments by age, sex and baseline cardiac comorbidities. Both systolic and diastolic blood pressure significantly increased over time with ibrutinib compared with baseline, whereas conventional chemoimmunotherapy was not associated with significant changes in blood pressure. Baseline hypertensive status did not affect the degree of blood pressure change over time. A significant increase in systolic blood pressure (defined as more than 10 mm Hg) was noted for ibrutinib (36.6%) compared with conventional chemoimmunotherapy (7.9%) at 1 month after treatment initiation. Despite being hypertensive at follow-up, 61.2% of patients who were treated with ibrutinib did not receive adequate blood pressure management (increase or addition of blood pressure medications). Within the ibrutinib group, of patients who developed more than 20 mm Hg increase in systolic blood pressure, only 52.9% had hypertension management changes.ConclusionsIbrutinib is associated with the development of hypertension and worsening of blood pressure. Cardiologists and oncologists must be aware of this cardiotoxicity to allow timely management of blood pressure elevations.

Cardiovascular Toxicities of Ibrutinib: A Pharmacovigilance Study Based on the United States Food and Drug Administration Adverse Event Reporting System Database

“…The above situations proved that HTN was not a robust signal. Several studies suggested that HTN is an adverse effect of ibrutinib [ 35 , 36 ]. The ibrutinib FDA label also indicated that in clinical trials of 1476 patients who received ibrutinib, HTN could occur in 19% of patients, and 8% of patients could experience grade 3 or higher HTN.…”

Ibrutinib versus bendamustine plus rituximab for first-line treatment of older patients with untreated chronic lymphocytic leukemia without del(17p)/TP53 mutation in China: A lifetime economic research study

“…Finally, our model may have underestimated the toxicity of IB, as some real-world studies have reported that treatment withdrawal rates and adverse effects were signi cantly higher compared to clinical trial data [41,42]. Furthermore, for patients with a history of hepatitis, treatment with IB may also lead to the reactivation of hepatitis virus infection [43,44].…”

Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension—Mechanisms and Mitigation

“…This could in part explain a concerning report that over 60% of patients treated with ibrutinib, who were hypertensive at follow-up did not receive an increase or any additional BP medications. 269 The consensus statement by the International Cardio-Oncology Society is an example of progress made to better adapt and modify recommendations for management of hypertension whilst incorporating CVD risk, BP thresholds for withholding anticancer treatment, and consideration of abrupt treatment-related hypertensive changes which may trigger initiation or escalation of treatment. 222 However, there remain inconsistencies between various guidelines and recommendations for optimal assessment and pharmacological management of hypertension, and there is growing need for large-scale clinical trials to further guide optimal individualized cancer and therapy-specific treatment pathways.…”