Ibrutinib Treatment Could Lead to Hypertension

A new study published in the journal Blood found that cancer patients treated with ibrutinib may have a greater risk for hypertension and other cardiovascular problems.

“Ibrutinib is associated with dramatic efficacy against B-cell malignancies. Yet, ibrutinib is linked with potentially-limiting cardiotoxicity, including emerging reports of profound hypertension. However, the long-term incidence, severity, and impacts of hypertension development during ibrutinib-use are unknown,” the study authors wrote in their report.

To investigate, the researchers evaluated data from 562 consecutive patients with B-cell malignancies who were treated with ibrutinib between 2009 and 2016 for new/incident or worsened hypertension, defined as a systolic blood pressure (BP) cutoff of 130 mmHg. They compared incident hypertension rates with Framingham heart predicted incident hypertension rates, and evaluated the preventative and modulatory effects of antihypertension medication based on medication class. The relationship between hypertension while taking ibrutinib and developing other major adverse cardiovascular events (MACE) was also examined; this included arrhythmias, myocardial infarction, stroke, heart failure, and cardiovascular death.

Nearly four in five (78.3%) of patients taking ibrutinib developed new or worsened hypertension (mean systolic BP increase 5.2 mmHg) over a median 30-month period. Further, 71.6% of patients (467 observed vs. 39 Framingham-predicted cases per 1,000 person-years) developed new hypertension; the time to 50% cumulative incidence was 4.2 months. Of the patients who did not have a history of hypertension, 17.7% developed high-grade hypertension, defined as BP 160/100 mmHg.

“This study provides a more clear picture of the extent of hypertension development among patients taking ibrutinib, while allowing us to tease out what ibrutinib-related hypertension means in the long run for other cardiovascular events and survival,” said senior study author Daniel Addison, MD, of the Ohio State Wexner Medical Center, in a press release. “Overall, both the magnitude and level of hypertension that developed was higher than previously thought and appears to portend a higher risk of other cardiac events.”

Multivariable regression analysis observed a relationship between new or worsened hypertension and increased MACE (hazard ratio [HR] 2.17, 95% confidence interval [CI] 1.08-4.38). While no single antihypertensive class was correlated with ibrutinib-related hypertension prevention or control, antihypertensive initiation decreased the risk for MACE (HR 0.40, 95% CI 0.24-0.66).

“It is important to emphasize that this is a lifesaving therapy with dramatic cancer treatment benefits, including improved survival; it has become ubiquitous to the treatment of many blood cancers and will continue to be applied to other cancers,” said Dr. Addison. “Accordingly, we need to find the best ways to manage high blood pressure and protect against other heart-related issues.”