Ibrutinib Linked with Adverse Cardiovascular Events: Analysis

Ibrutinib administration was associated with a number of severe cardiac events, results from a new analysis suggest.

“Ibrutinib has revolutionized treatment for several B-cell malignancies,” the researchers wrote. “However, a recent clinical trial where [it] 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.”

The paper authors sought to characterize cardiovascular adverse drug reactions associated with the commonly used therapy. Using the VigiBase (international pharmacovigilance database), the authors performed disproportionality analyses using reporting odds ratios and information component to assess possible associations between the drug, cardiovascular adverse drug reactions and deaths linked to those reactions. Information component compared observed and expected results, and used disproportionate Bayesian reporting to assess differences. The results were published in the Journal of the American College of Cardiology.

According to the results, there were 303 ibrutinib-associated cardiovascular deaths. The drug was linked to higher reporting of supraventricular arrhythmias (P<0.0001), central nervous system hemorrhagic events (P<0.0001), heart failure (P<0.0001), ventricular arrhythmias (P<0.0001), conduction disorders (P<0.0001), central nervous system ischemic events (P<0.0001), and hypertension (P<0.0001). According to the authors, cardiovascular adverse drug reactions “often occurred after ibrutinib administration.” The also pointed out that cardiovascular adverse drug reactions were associated with fatalities that were related to the conditions, from about 10% with supraventricular arrhythmias and ventricular arrhythmias to about 20% with central nervous system events, heart failure, and conduction disorders. The reported specifically that ibrutinib-linked supraventricular arrhythmias carry a particularly poor prognosis when central nervous system events occur concomitantly (28.8% deaths; 15 of 52 cases).

“Severe and occasionally fatal cardiac events occur in patients exposed to ibrutinib,” the authors wrote in their abstract. “These events should be considered in patient care and in clinical trial designs.”