The oncologist would like to enroll the patient in a randomized controlled trial with novel Bruton's tyrosine kinase (BTK) inhibitor zanubrutinib. The patient is sent to cardiology for cardiovascular (CV) optimization and risk stratification.
Which one of the following statements is correct?
Show Answer
The correct answer is: D. A and B.
Ibrutinib and, to a lesser extent, other BTK inhibitors (acalabrutinib, zanubrutinib) are associated with an increased risk of hypertension and AF. Ventricular arrhythmias have also been reported. In a retrospective study of 562 patients treated with ibrutinib, 72% developed new hypertension and the development of hypertension was associated with a twofold increased risk of major adverse cardiovascular events (MACE). Importantly, the use of antihypertensives reduced the risk of MACE. AF is the major CV toxicity associated with BTK inhibitors. In a pooled meta-analysis of randomized controlled trials, ibrutinib was associated with a fourfold increased risk of AF compared with non-BTK therapies. The overall incidence of AF was 11.2% after 36 months of follow-up. Although most patients do not require hospitalization for AF, some patients may need dose reduction or permanent discontinuation of the BTK inhibitor for refractory or severe AF. Risk factors for AF include older age, male sex, pre-existing hypertension, history of AF, and valvular heart disease. However, these are not contraindications for the use of BTK inhibitors.
Drs. Jennifer R. Brown, MD, PhD; John Fanikos, RPH, MBA; Michael G. Fradley, MD served as peer reviewers for this patient case.
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References
Dickerson T, Wiczer T, Waller A, et al. Hypertension and incident cardiovascular events following ibrutinib initiation. Blood 2019;134:1919-28.
Brown JR, Moslehi J, O'Brien S, et al. Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials. Haematologica 2017;102:1796-805.
Yun S, Vincelette ND, Acharya U, Abraham I. Risk of atrial fibrillation and bleeding diathesis associated with ibrutinib treatment: a systematic review and pooled analysis of four randomized controlled trials. Clin Lymphoma Myeloma Leuk 2017;17:31-37.e13.
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