Atrial fibrillation, anticoagulant stroke prophylaxis and bleeding risk with ibrutinib therapy for chronic lymphocytic leukaemia and lymphoproliferative disorders

Cumulative incidence, risk factors, and management of atrial fibrillation in patients receiving ibrutinib

“…[5][6][7][8][9][10] AF has been identified as a particularly concerning adverse effect impacting 2% to 16% of patients with CLL, MCL, and WM treated with ibrutinib. [1][2][3]5,[11][12][13][14][15][16][17][18][19][20][21][22] A recent meta-analysis has demonstrated a pooled incidence rate of 3.3 per person-years (95% confidence interval [CI] 2.5-4.1) among ibrutinib recipients. This rate is substantially higher than clinical trial participants receiving nonibrutinib therapy (0.84 per 100 person-years with 95% CI 0.32-1.6) and the general population of men and women aged 65 to 74 years (1.8 and 1.0 per 100 personyears, respectively).…”

“…20,23 Available literature also suggests that most patients develop AF within the first 4 months of ibrutinib treatment. [16][17][18][19][20][21] The fundamental principles of managing patients with AF are rate or rhythm control and stroke prevention. 24 Stroke prevention in patients with AF who are taking ibrutinib is complicated by the inherent bleeding risk associated with ibrutinib treatment, and there are no clear guidelines on use of anticoagulants or antiplatelet agents in this population.…”

“…25 Comprehensive studies evaluating risk factors for the development of AF during ibrutinib treatment are limited by the small number of cases, but have suggested preexisting diabetes, hypertension, and prior history of AF as potentially significant risk factors. [16][17][18][19][20][21] However, the risk of AF in the setting of ibrutinib treatment is poorly understood.…”

Recommendations for ibrutinib treatment in patients with atrial fibrillation and/or elevated cardiovascular risk

“…Ibrutinib is currently not recommended in patients who require therapy with vitamin K antagonists (VKA) like warfarin, but patients treated with non-oral anticoagulants (heparin, low-molecular weight heparin, LMWH) or direct oral anticoagulants (DOAC, also known as non-vitamin K oral anticoagulants, NOAC) were not excluded in clinical trials. Likewise, antiplatelet agents, including aspirin, clopidogrel and non-steroidal anti-inflammatory drugs (NSAIDs) could be administered in ibrutinib trials; however, concurrent use of antiplatelet agents resulted in increased rates of bleeding [38]. Furthermore, increased bleeding risk has also been reported occasionally with other drugs known to inhibit platelet function, including vitamin E [9] and fish oil [17].…”

“…These effects of ibrutinib on platelet function might lead to improved outcomes in patients with elevated cardiovascular risk, and it is possible that antiplatelet agents in patients receiving ibrutinib therapy could be discontinued. This strat-egy could subsequently hypothetically decrease cardiovascular events and bleeding; however, there is currently insufficient data to suggest that ibrutinib could indeed be used for primary or secondary cardiovascular risk reduction [29,38].…”