Combination therapy with two or more antihypertensive drugs may reduce blood pressure in patients receiving ibrutinib, according to a recent study published by Samples et al in Blood Advances.
Background
Ibrutinib was the first Bruton tyrosine kinase (BTK) inhibitor to receive U.S. Food and Drug Administration (FDA) approval to treat patients with mantle cell lymphoma, chronic lymphocytic leukemia, and certain other lymphoid cancers.
Targeted therapies such as ibrutinib have shown potential for improving outcomes in patients with these types of malignancies.
“[However], several studies have shown that BTK [inhibitors] can cause patients to develop new or worsening [hypertension],” explained lead study author Laura Samples, MD, of Fred Hutchinson Cancer Center and the University of Washington School of Medicine. “One study found this to be the case in over 78% of patients treated with ibrutinib over a median of 30 months. Uncontrolled … hypertension can lead to major adverse cardiovascular events such as heart attack, heart failure, and stroke,” she added.
Few studies have focused on the most effective strategies to treat this potentially severe side effect, and there are currently no formal guidelines to help physicians treat this patient population.
“To our knowledge, this is the first and only study to examine how to optimally treat [hypertension] in patients receiving ibrutinib,” highlighted senior study author Mazyar Shadman, MD, MPH, of Fred Hutchinson Cancer Center and the University of Washington School of Medicine.
Study Methods and Results
In the recent study, investigators examined the medical records of 196 patients with an average age of 67 years who were concurrently treated with a BTK inhibitor and one or more antihypertensive drugs for at least 3 months between 2014 and 2018. The investigators noted that 93% of the patients identified as White, 71% of them were male, and 29% of them were female. The primary outcome of the study was the effectiveness of antihypertensive drugs as assessed by the average reduction in mean arterial pressure.
The investigators revealed that different drug combinations may have been more effective depending on whether the patients had hypertension prior to initiating treatment with ibrutinib or developed hypertension while taking the drug.
They divided the patients into two groups: those who were taking at least one antihypertensive drug prior to starting treatment with a BTK inhibitor (n = 118) and those who began taking one or more antihypertensive drugs during treatment with a BTK inhibitor (n = 78). They then categorized antihypertensive drugs into four groups: angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers, beta blockers, calcium channel blockers, and hydrochlorothiazide.
The investigators demonstrated that patients who were taking beta blockers along with hydrochlorothiazide prior to BTK inhibitors achieved statistically significant average reductions of about 5 mmHg in their mean arterial pressure. The patients who started taking ACE inhibitors or angiotensin receptor blockers along with hydrochlorothiazide during treatment with BTK inhibitors achieved similar reductions in their mean arterial pressure. About 15% of the patients in both groups who were taking beta blockers and hydrochlorothiazide reached what the investigators classified as a normal blood pressure range (120/80 or lower).
Conclusions
“Our results reinforce that in this patient population—as in, patients with hypertension in general—[physicians] need to treat with multiple drugs to achieve successful blood pressure control,” suggested Dr. Samples.
The investigators stressed that the new research didn’t explore why certain combination regimens were more effective than others or why different combination regimens were most effective in patients with preexisting and new-onset hypertension
“[Nonetheless], we now have some data that other researchers can analyze to perhaps find answers to these questions,” Dr. Shadman indicated. “Our findings strongly suggest that aggressive treatment with certain combinations of antihypertensive [drugs] can achieve significantly reduced blood pressures in this patient population,” he underscored.
Because the study was retrospective, larger prospective studies may be needed to develop formal guidelines on the most effective antihypertensive regimens in patients receiving BTK inhibitors.
Additionally, the patients’ blood pressure was measured only during clinic visits. Studies have shown that blood pressure measurements taken in physicians’ offices or other clinical settings can produce varying results.
“Future studies should, if possible, measure patients’ blood pressure using wearable devices that measure blood pressure over a 24-hour period,” Dr. Shadman proposed.
The investigators also emphasized that 90% of the patients in the study were taking ibrutinib and 10% of them were treated with acalabrutinib or other, newer BTK inhibitors such as zanubrutinib—which received its initial FDA approval in 2019. The data used in 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. Given that [hypertension] is a class effect of treatment with BTK [inhibitors], both [physicians] 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,” Dr. Samples concluded.
Disclosure: The research in this study was funded by AstraZeneca. For full disclosures of the study authors, visit ashpublications.org.
