AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Incidence, Risk Factors, and Mortality Outcomes of Incident Atrial Fibrillation After Tyrosine Kinase Inhibitor Therapy: An All of Us Research Program Analysis
By Moeed A, Ghazi S, Jupelly R et al.
Introduction: Tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment, but the incidence, predictors, and clinical impact of atrial fibrillation (AF) following TKI initiation remain poorly defined. Methods: Using the US National Institute of Health (NIH)’s prospective All of Us Research Program, we identified all cancer patients initiating TKIs from 2018 to 2023. The primary outcome was incident AF. Secondary outcomes were major adverse cardiovascular events (MACE: heart failure, arrhythmia, myocardial infarction, stroke, or cardiac arrest) and all-cause mortality. Multivariable Cox models adjusted for demographic, cardiovascular, oncologic, and treatment covariates. Observed incident AF rates were compared with matched cancer patients without TKI treatment (cancer-controls) and to similar-aged non-cancer participants (cancer-controls) using All of Us , relative risks. Absolute excess risks (AER) of AF were estimated. Further, we explored the effects of different cardioprotective classes on AF-development. Results: Among 10,619 participants (3,119 TKI-treated patients and 7,500 matched controls), 300 out of 2,733 TKI-treated patients without baseline AF developed incident AF (10.9%; median time, 31.0 months), compared with 325 controls (4.9%). TKI therapy was associated with increased AF risk (IRR 1.47, 95% CI 1.35-1.90; P<0.001), corresponding to 71 excess AF events per 10,000 person-years; ( Figure 1) . Elevated risk persisted after excluding Bruton TKI-treated patients (IRR 1.92, 95% CI 1.64-2.25; P<0.001. Among TKI-treated patients, incident AF independently predicted MACE (aHR 4.29, 95% CI 2.30-8.00; P<0.0001) and all-cause mortality (aHR 1.94, 95% CI 1.22-3.10; P=0.005). New/worsened hypertension was independently associated with MACE (HR 1.61, 95% CI 1.28-2.03; P<0.001) and AF (HR 1.75, 95% CI 1.30-2.40; P<0.001), including after BTKI exclusion (HR 1.65, 95% CI 1.20-2.30; P=0.003). No specific cardiac drug class was associated with the prevention of TKI-related AF. Conclusions: Incident AF after TKI initiation is common, exceeded rates observed in matched non-cancer controls, and independently predicted subsequent cardiovascular events and mortality. These findings support systematic cardiovascular surveillance in TKI-treated cancer patients, particularly those with baseline cardiovascular disease or new/worsened hypertension.