Over half of patients treated with the Bruton’s tyrosine kinase inhibitor ibrutinib developed new or worsened high blood pressure within 6 months of starting the medication, according to a study published by Dickerson et al in Blood. The analysis is also the first to tie ibrutinib-related hypertension to a heightened risk of heart problems; particularly, atrial fibrillation. Moreover, the association of ibrutinib with cardiovascular complications remained, regardless of the prescribed dose.

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Ibrutinib is approved to treat several types of blood cancers; it is currently being studied in nearly 200 clinical trials, including in over 10 different types of solid tumor malignancies.

“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 University Comprehensive Cancer Center Cancer Control Research Program. “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.”

Methods

For this single-center study, researchers analyzed medical records for 562 consecutive patients treated with ibrutinib for B-cell hematologic malignancies at The Ohio State University Comprehensive Cancer Center between 2009 and 2016 to assess the incidence of new or worsened hypertension as well as the relationship with other cardiovascular outcomes. Patients were aged 64 years old, on average; most were male and had chronic lymphocytic leukemia. New hypertension was defined as systolic blood pressure of ≥ 130 mmHg per the 2017 American College of Cardiology/American Heart Association lowered cut-off and had to be evident on two separate visits within 3 months.

Results

Nearly 72% of patients treated with ibrutinib developed new-onset hypertension over a median follow-up of 30 months; of these, 18% had blood pressure readings of over 160/100mmHg. Evidence of rising blood pressure was evident soon after start of therapy among people without preexisting hypertension; the rate of new hypertension was 54% within 6 months, with an overall average increase in systolic blood pressure of 13 mmHg. When researchers compared new cases of hypertension to what would be expected using a traditional risk prediction model using previously less strict blood pressure cut-offs, hypertension was nearly 13 times higher at 1 year among people treated with ibrutinib compared with people of similar age and heart conditions not taking the drug.

Antihypertensive medication was prescribed or increased in more than one-third of patients on ibrutinib, with nearly one in five requiring three or more medications. Cardiovascular complications were more than twice as common (19.1% vs 8.2%) among people treated with ibrutinib who had worsened blood pressure compared with those who did not see worsened blood pressure. Atrial fibrillation was the most common heart issue, followed by new heart failure, stroke, heart attack, and other heart rhythm problems, including sudden cardiac death.

“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.”

Because this was a retrospective study, blood pressure measures and decisions to start blood pressure–lowering medications varied by treating physician. Additional prospective studies are needed to understand whether the change in blood pressure could be used as a surrogate to direct treatment and to find optimal strategies to lower cardiovascular risk among these patients, the researchers clarified.

Disclosure: For full disclosures of the study authors, visit ashpublications.org.