Ibrutinib Linked to Hypertension, Subsequent Cardiotoxic Events

October 4, 2019
Over half of people prescribed the targeted blood cancer-fighting drug ibrutinib develop new or worsened hypertension within 6 months of starting the medication, according to a study published in Blood. The analysis also tied 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. “This study provides a [clearer] 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 Daniel Addison, MD, Ohio State Wexner Medical Center, Columbus, Ohio. “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.” For the study, Tyler Dickerson, Ohio State University, Columbus, Ohio, and colleagues analysed medical records for 562 patients treated with ibrutinib for B-cell cancers at Ohio State University’s 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 on average, were mostly male, and had chronic lymphocytic leukaemia. New hypertension was defined as systolic blood pressure of 130 mm Hg per the 2017 American College of Cardiology/American Heart Association lowered cut-off, and had to be evident on 2 separate visits within 3 months. The researchers found that over a median of 30 months, 78.3% of patients taking ibrutinib developed new or worsened hypertension. New hypertension developed in 71.6% of patients taking ibrutinib, with a time-to-50% cumulative incidence of 4.2 months. Among those without preceding hypertension, 17.7% developed high-grade hypertension. In multivariable regression containing known predictors of major adverse cardiovascular events (MACE) including arrhythmias, myocardial infarction, stroke, heart failure, and cardiovascular death, new or worsened hypertension was associated with increased MACE (hazard ratio [HR] = 2.17; 95% confidence interval [CI], 1.08-4.38]. No single-antihypertensive class was associated with prevention or control of ibrutinib-related hypertension. However, antihypertensive initiation was associated with a lower risk of MACE (HR = 0.40; 95% CI, 0.24-0.66). Collectively, these data suggest that ibrutinib is associated with a substantial increase in the incidence and severity of hypertension, and that hypertension development may suggest a higher risk of subsequent cardiotoxic events. “It is important to emphasise that this is a life-saving therapy with dramatic cancer treatment benefits, including improved survival,” concluded Dr. Addison. “It has become ubiquitous to the treatment of many blood cancers and will continue to be applied to other cancers. Accordingly, we need to find the best ways to manage [hypertension] and protect against other heart-related issues.” Since 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. Reference: https://doi.org/10.1182/blood.2019000840 SOURCE: American Society of Hematology