In this sense, second-generation Bruton tyrosine kinase inhibitors reported an improved safety profile, with substantially lower incidence of atrial fibrillation when using zanubrutunib vs. ibrutinib in the ALPINE study [56] and a significantly lower incidence of atrial fibrillation, hypertension, and bleeding, as well as diarrhoea, arthralgia, urinary tract infection, back pain, muscle spasms, and dyspepsia, when using acalabrutinib vs. ibrutinib in the ELEVATE RR study [57]. This evidence concerns the gene BTK and atrial fibrillation.