Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Add like
Add dislike
Add to saved papers

Cardiovascular Toxicities Associated With Ibrutinib.

BACKGROUND: Ibrutinib has revolutionized treatment for several B-cell malignancies. However, a recent clinical trial where ibrutinib was used in a front-line setting showed increased mortality during treatment compared with conventional chemotherapy. Cardiovascular toxicities were suspected as the culprit but not directly assessed in the study.

OBJECTIVES: The purpose of this study was to identify and characterize cardiovascular adverse drug reactions (CV-ADR) associated with ibrutinib.

METHODS: This study utilized VigiBase (International pharmacovigilance database) and performed a disproportionality analysis using reporting odds ratios (ROR) and information component (IC) to determine whether CV-ADR and CV-ADR deaths were associated with ibrutinib. IC compares observed and expected values to find associations between drugs and adverse drug reactions using disproportionate Bayesian-reporting; IC025 (lower end of the IC 95% credibility interval) >0 is significant.

RESULTS: This study identified 303 ibrutinib-associated cardiovascular deaths. Ibrutinib was associated with higher reporting of supraventricular arrhythmias (SVAs) (ROR: 23.1; 95% confidence interval: 21.6 to 24.7; p < 0.0001; IC025 : 3.97), central nervous system (CNS) hemorrhagic events (ROR: 3.7; 95% confidence interval: 3.4 to 4.1; p < 0.0001; IC025 : 1.63), heart failure (ROR: 3.5; 95% confidence interval: 3.1 to 3.8; p < 0.0001; IC025 : 1.46), ventricular arrhythmias (ROR: 4.7; 95% confidence interval: 3.7 to 5.9; p < 0.0001; IC025 : 0.96), conduction disorders (ROR: 3.5; 95% confidence interval: 2.7 to 4.6; p < 0.0001; IC025 : 0.76), CNS ischemic events (ROR: 2.2; 95% confidence interval: 2.0 to 2.5; p < 0.0001; IC025 : 0.73), and hypertension (ROR: 1.7; 95% confidence interval: 1.5 to 1.9; p < 0.0001; IC025 : 0.4). CV-ADR often occurred early after ibrutinib administration. Importantly, CV-ADR were associated with fatalities that ranged from ∼10% (SVAs and ventricular arrhythmias) to ∼20% (CNS events, heart failure, and conduction disorders). Ibrutinib-associated SVA portends poor prognosis when CNS events occur concomitantly, with 28.8% deaths (15 of 52 cases).

CONCLUSIONS: Severe and occasionally fatal cardiac events occur in patients exposed to ibrutinib. These events should be considered in patient care and in clinical trial designs. (Evaluation of Reporting of Cardio-vascular Adverse Events With Antineoplastic and Immunomodulating Agents [EROCA]; NCT03530215).

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

Related Resources

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app