Association Between the Renin-Angiotensin System and Ibrutinib-Related Cardiovascular Adverse Events: A Translational...

Area of Science:

• Cardiovascular Medicine
• Oncology
• Pharmacology

Background:

• Ibrutinib treatment is linked to increased cardiovascular adverse events (CVAEs), including atrial fibrillation, hypertension, heart failure, and ventricular arrhythmias.
• Predictors of these ibrutinib-related CVAEs are not well understood, particularly concerning the renin-angiotensin system.

Purpose of the Study:

• To identify baseline patient characteristics associated with ibrutinib-related CVAEs.
• To investigate the specific role of renin-angiotensin system parameters in predicting CVAEs during ibrutinib therapy.

Main Methods:

• Prospective, single-center cohort study of patients with B-cell malignancy receiving ibrutinib.
• Systematic assessment of baseline demographic, clinical, biomarker (inflammation, fibrosis, neurohormonal), and echocardiographic parameters.
• Composite CVAE endpoint included atrial fibrillation, new/worsening hypertension, new/worsening heart failure, and ventricular arrhythmias.

Main Results:

• Seven of 25 patients experienced a total of 9 CVAEs during a median follow-up of 672 days.
• Elevated baseline plasma renin levels (>1336.10 pg/mL) were significantly associated with CVAE occurrence (57% vs. 11%, p=0.032).
• Higher baseline plasma aldosterone levels were observed in patients with CVAEs, but this did not reach statistical significance (p=0.058).

Conclusions:

• Baseline plasma renin level is a univariable predictor of CVAEs in ibrutinib-treated patients.
• Plasma aldosterone levels showed a trend towards association with CVAEs.
• Findings suggest a potential role for the renin-angiotensin-aldosterone system in ibrutinib-induced cardiovascular toxicity, warranting further investigation in larger studies.