New Study Suggests Effective Management Strategies for High Blood Pressure with Imbruvica

Combination therapy with certain classes of blood pressure medications may effectively lower blood pressure in patients taking ibrutinib (Imbruvica), according to new research published February 5th in the journal Blood Advances. The study showed that different combinations of antihypertensive drugs were more effective depending on whether people had high blood pressure before starting Imbruvica or if they developed it while taking the drug.

Imbruvica is an oral medication prescribed to treat certain B-cell malignancies, including chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and Waldenstrom macroglobulinemia. Approved in 2013, Imbruvica became the first Bruton’s tyrosine kinase inhibitor (BKTi) on the market and has shown dramatic effectiveness against B-cell malignancies.

However, the benefit of Imbruvica and other drugs in its class are limited by cardiovascular risks including severely high blood pressure. More than 78% of patients taking Imbruvica eventually develop new or worsened hypertension. Uncontrolled blood pressure is associated with a heightened risk of major adverse events including heart attack. Currently, there are no guidelines for clinicians on how to best manage this side effect.

The new study aimed to determine if a specific antihypertensive drug class or a combination of classes would effectively reduce hypertension in people who developed high blood pressure before or after starting Imbruvica.

“To our knowledge, this is the first and only study to examine how to optimally treat high blood pressure in patients receiving ibrutinib,” senior author Mazyar Shadman, M.D., M.P.H., blood cancer specialist at the Fred Hutch Cancer Center and professor at the University of Washington School of Medicine, said in a press release.

To explore how best to treat this potentially serious side effect, Shadman and colleagues conducted a retrospective, multi-center study utilizing real world data from the medical records of nearly 200 patients. They randomly selected the records of patients with lymphoid cancers and hypertension who were treated with ibrutinib or another BTKi and blood pressure medications for at least three months between 2014 and 2018.

The investigators divided the patients into two groups: those who had pre-existing hypertension and those who developed hypertension for the first time after starting BTKi treatment. They analyzed data such as demographic variables, comorbidities, specific malignancy type, treatment timelines, documentation of BTKi treatment changes or discontinuation, as well as the types of anti-hypertensive medications used.

The results of their analysis showed that the patients who took a combination of antihypertensive medications had the greatest reductions in blood pressure. Taking two or more drugs seemed to be the most effective in achieving control. Two specific combination regimens stood out. Beta blockers plus hydrochlorothiazide (“HCTZ,” a diuretic) showed a statistically significant average blood pressure reduction in patients with pre-existing hypertension.

Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) plus HCTZ showed a statistically significant average reduction in patients who developed high blood pressure post-initiation of ibrutinib.

“Our findings strongly suggest that aggressive treatment with certain combinations of antihypertensive medications can achieve significantly reduced blood pressures in this patient population,” Shadman stated in the press release.

In their paper, the authors concluded that large prospective studies will be necessary to formalize guidelines for effectively managing hypertension in this patient population.