A new study has suggested that combination treatments with two or more blood pressure drugs can significantly reduce blood pressure in patients taking ibrutinib.
Targeted drugs such as ibrutinib have improved outcomes for patients with cancers of the lymphatic system. However, patients treated with this, and other drugs in its class, known as Bruton tyrosine kinase inhibitors (BTKis), often develop new or worsening high blood pressure.
Ibrutinib has been on the market since 2013, and was the first drug in its class to receive FDA approval to treat patients with mantle cell lymphoma, chronic lymphocytic leukemia and certain other lymphoid cancers.
To date there has been limited research on how best to treat this serious side effect of high blood pressure, and no formal guidelines exist for doctors looking to find the most effective treatments.
Published in Blood Advances, this new study found that different drug combinations may be more effective depending on whether patients had high blood pressure before starting treatment with ibrutinib, or developed high blood pressure while taking the drug.
Mazyar Shadman, MD, MPH, of Fred Hutchinson Cancer Center and the University of Washington School of Medicine, and the study’s senior author, commented: “To our knowledge, this is the first and only study to examine how to optimally treat high blood pressure in patients receiving ibrutinib.
“Our findings strongly suggest that aggressive treatment with certain combinations of antihypertensive medications can achieve significantly reduced blood pressures in this patient population.”
“Several studies have shown that BTKis can cause patients to develop new or worsening high blood pressure,” added Laura Samples, MD, also of Fred Hutchinson Cancer Center and the University of Washington School of Medicine, and the study’s first author.
“One study found this to be the case in over 78% of patients treated with ibrutinib over a median of 30 months. Uncontrolled high blood pressure, or hypertension, can lead to major adverse cardiovascular events, such as heart attack, heart failure, and stroke.”
Results showed that patients in the group taking at least one antihypertensive medication before starting treatment with a BTKi, who took beta blockers along with hydrochlorothiazide, achieved statistically significant average reductions in MAP of about five mmHg.
Patients in the de novo HTN group (the group that developed new onset high blood pressure after starting treatment) who took ACE inhibitors or ARBs along with hydrochlorothiazide achieved similar reductions in MAP.
Approximately 15% of patients in both groups taking beta blockers and hydrochlorothiazide reached what researchers classified as a normal blood pressure range.
“Our results reinforce that – in this patient population as in patients with hypertension in general – you need to treat with multiple drugs to achieve successful blood pressure control,” said Samples.
Combination treatments
The study findings do not shed any light on why certain combination regimens were more effective than others or why different combination regimens were most effective in patients with pre-existing and new-onset hypertension.
Shadman added. “But we now have some data that other researchers can analyse to perhaps find answers to these questions.”
The researchers highlight that a limitation of the study is that it is retrospective, and Samples emphasised that large prospective studies are needed to develop formal guidelines on the most effective antihypertensive regimens in patients taking BTKis.
Secondly, patients’ blood pressure was measured only during clinic visits. Studies have shown that blood pressure measurements taken in doctors’ offices or other clinical settings can produce varying results, with the researchers encouraging monitoring of blood-pressure over a 24 hour period in future studies.
Finally, nearly 90% of patients in the study were taking ibrutinib. The rest were treated with acalabrutinib or other, newer BTKi’s such as zanubrutinib, which received its initial FDA approval in 2019.
Data for the study came from a period when ibrutinib was still more common than its second-generation counterparts.
“Studies suggest that patients taking these newer agents still face an increased risk of major adverse cardiovascular events, although the risk may be lower than that of ibrutinib,” Samples said.
“Given that increased blood pressure is a “class effect” of treatment with BTKis, both doctors and patients need to be aware of this risk and patients’ blood pressure should be monitored regularly so that treatment can begin immediately when an increase is detected.”
