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Association between ibrutinib treatment and hypertension
  1. Dae Hyun Lee1,
  2. Fahad Hawk1,
  3. Kieun Seok2,
  4. Matthew Gliksman3,
  5. Josephine Emole4,
  6. Isaac B Rhea5,
  7. Federico Viganego6,
  8. Allan Welter-Frost1,
  9. Merna Armanious1,
  10. Bijal Shah7,
  11. Juliio C Chavez7,
  12. Javier Pinilla-Ibarz7,
  13. Matthew B Schabath8,
  14. Michael Fradley9
  1. 1 Division of Cardiovascular Medicine, University of South Florida College of Medicine, Tampa, Florida, USA
  2. 2 Department of Internal Medicine, University of South Florida College of Medicine, Tampa, Florida, USA
  3. 3 University of South Florida Morsani College of Medicine, Tampa, Florida, USA
  4. 4 Department of Medical Oncology, Henry Ford Health System, Detroit, Michigan, USA
  5. 5 Cardio-Oncology Division, University of Tennessee Health Science Center Bookstore, Memphis, Tennessee, USA
  6. 6 Cardio-Oncology Program, University of South Florida College of Medicine, Tampa, Florida, USA
  7. 7 Malignant Hematology Program, Moffitt Cancer Center, Tampa, Florida, USA
  8. 8 Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA
  9. 9 Cardio-Oncology Center of Excellence, Division of Cardiology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
  1. Correspondence to Dr Michael Fradley, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Michael.Fradley{at}


Background Ibrutinib is a tyrosine kinase inhibitor most commonly associated with atrial fibrillation. However, additional cardiotoxicities have been identified, including accelerated hypertension. The incidence and risk factors of new or worsening hypertension following ibrutinib treatment are not as well known.

Methods We conducted a retrospective study of 144 patients diagnosed with B cell malignancies treated with ibrutinib (n=93) versus conventional chemoimmunotherapy (n=51) and evaluated their effects on blood pressure at 1, 2, 3 and 6 months after treatment initiation. Descriptive statistics were used to compare baseline characteristics for each treatment group. Fisher’s exact test was used to identify covariates significantly associated with the development of hypertension. Repeated measures analyses were conducted to analyse longitudinal blood pressure changes.

Results Both treatments had similar prevalence of baseline hypertension at 63.4% and 66.7%, respectively. There were no differences between treatments by age, sex and baseline cardiac comorbidities. Both systolic and diastolic blood pressure significantly increased over time with ibrutinib compared with baseline, whereas conventional chemoimmunotherapy was not associated with significant changes in blood pressure. Baseline hypertensive status did not affect the degree of blood pressure change over time. A significant increase in systolic blood pressure (defined as more than 10 mm Hg) was noted for ibrutinib (36.6%) compared with conventional chemoimmunotherapy (7.9%) at 1 month after treatment initiation. Despite being hypertensive at follow-up, 61.2% of patients who were treated with ibrutinib did not receive adequate blood pressure management (increase or addition of blood pressure medications). Within the ibrutinib group, of patients who developed more than 20 mm Hg increase in systolic blood pressure, only 52.9% had hypertension management changes.

Conclusions Ibrutinib is associated with the development of hypertension and worsening of blood pressure. Cardiologists and oncologists must be aware of this cardiotoxicity to allow timely management of blood pressure elevations.

  • outcome assessment
  • health care
  • drug monitoring
  • hypertension

Data availability statement

No data are available.

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Data availability statement

No data are available.

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  • Twitter @daehyunleemd, @dr_mike_fradley

  • DHL and FH contributed equally.

  • Presented at Preliminary data were presented at the American Heart Association Scientific Sessions of 2019 as a poster presentation.

  • Contributors Planning of work: DHL, BS, JCC, JP-I, MBS, MF. Conduct of work: DHL, FH, KS, MG, JE, IBR, FV, AW-F, MA, MBS, MF. Reporting of work: DHL, FH, KS, BS, JCC, JP-I, MBS, MF.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests MF is advisor/consultant for Takeda and Abbott and received research grant from Medtronic. JP-I is investigator for Novartis and Ariad; consultant/advisor for Novartis, Bristol-Myers Squibb and Ariad; and received consulting/speakers bureau fees from Janssen and Pharmacyclics. The rest of the authors have nothing to disclose.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; internally peer reviewed.