Ibrutinib and other Bruton tyrosine kinase inhibitors can cause the development of or worsen pre-existing hypertension.
The combination of taking 2 or more blood pressure medications can significantly reduce blood pressure for patients who are taking ibrutinib, according to results of a study published in Blood Advances.1,2
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Ibrutinib has been shown to improve outcomes for patients with lymphatic cancers, although the drug and other Bruton tyrosine kinase inhibitors (BTKi) can cause the patient to develop or worsen pre-existing hypertension, according to a press release from the American Society of Hematology. Previously, there have been few studies that showed how to treat the adverse event and there are no formal guidelines for treatment.1
3 Key Takeaways
This study suggests that combining two or more blood pressure medications can significantly reduce blood pressure levels in these patients.
Beta blockers, hydrochlorothiazide, and ACE inhibitors or ARBs with hydrochlorothiazide were particularly effective.
Physicians and patients need to be vigilant about monitoring blood pressure regularly during ibrutinib treatment.
“To our knowledge, this is the first and only study to examine how to optimally treat high blood pressure in patients receiving ibrutinib,” Mazyar Shadman, MD, MPH, of Fred Hutchinson Cancer Center and the University of Washington School of Medicine, said in the press release. “Our findings strongly suggest that aggressive treatment with certain combinations of antihypertensive medications can achieve significantly reduced blood pressures in this patient population.”1
In the study, investigators analyzed medical records of 196 individuals who were treated with a BTKi and one or more antihypertensive medications for at least 3 months, according to the press release. The study ranged from 2014 to 2018 at 1 of 14 US medical centers. Approximately 93% of patients were white and the mean age was 67 years old. Approximately 71% were male. Approximately 90% were taking ibrutinib, and the rest were treated with acalabrutinib or newer BTKi’s, including zanubrutinib.1
The study investigators separated individuals into 2 groups that either took at least 1 antihypertensive medication before BTKi treatment (pre-existing condition), which included 118 individuals, and those who began taking 1 or more antihypertensive medications while being treated with a BTKi (after drug initiation), which included 78 individuals.1
Antihypertensive medications were categorized as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), beta blockers, calcium blockers, and hydrochlorothiazide, according to the press release. Primary endpoints included the effectiveness of antihypertensive treatment assessed by the average reduction in mean arterial pressure.1
“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,” Laura Samples, MD, also of Fred Hutchinson Cancer Center and the University of Washington School of Medicine, said in the press release.1
For those who had prior hypertension, beta blockers and hydrochlorothiazide achieved statistically significant average reductions in mean arterial pressure at approximately 5 mmHg, according to the press release. For those who developed hypertension after BTKi, ACE inhibitors or ARBs with hydrochlorothiazide had similar reductions. Approximately 15% of those in both groups who took beta blockers and hydrochlorothiazide achieved a normal blood pressure range of 120 over 80 or lower, according to the press release.1
“Given that increased blood pressure is a 'class effect' of treatment with BTKis, 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,” Samples said in the press release.1
Limitations of the study, according to investigators, included that the study was retrospective, so larger prospective studies are needed to inform guidelines. Further, the blood pressure measurements were only taken during visits to the clinic, according to the press release.1
Combination therapy lowers blood pressure in patients receiving ibrutinib. News release. American Society of Hematology. February 5, 2024. Accessed February 6, 2024. https://www.hematology.org/newsroom/press-releases/combination-therapy-lowers-blood-pressure-in-patients-receiving-ibrutinib
Samples L, Voutsinas JM, Fakhri B, Fakhri B, et al. Hypertension Treatment in Patients Receiving Ibrutinib: A Multicenter Retrospective Study. Blood Adv. doi:10.1182/bloodadvances.2023011569