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Caution: ibrutinib in patients with cardiac risk

Ibrutinib raises the risk of irregular heart rhythm, high blood pressure, and sudden cardiac events; second-generation BTK inhibitors are safer choices for patients with heart disease.

Atrial fibrillation 10-16%, hypertension ~40% cumulative, and ventricular arrhythmia/sudden death signals in long-term ibrutinib data; ELEVATE-RR and ALPINE showed roughly half the atrial fibrillation with acalabrutinib and zanubrutinib. Anticoagulation for AF adds bleeding risk with any BTKi.

Rationale
Off-target inhibition of CSK and TEC in cardiomyocytes and vasculature.
Evidence
Head-to-head phase 3 (ELEVATE-RR, ALPINE); pharmacovigilance.

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