Impact of Real-world Off-label dose of Apixaban on long-term clinical outcomes in Atrial Fibrillation patients with Heart failure and Chronic Kidney Disease

Abstract Background Apixaban represent one of the cornerstone treatments to prevent cardioembolic events in patients with nonvalvular atrial fibrillation (NVAF). However, the choices of Apixaban dose guided by the decision-making process of the physician, which considers specific according to kidney functions are inconsistent in the real-world practice. Purpose The objective of the present study is to evaluate the effects of real-world Off-label dose of Apixaban on long-term clinical outcomes in NVAF patients with heart failure (HF) and chronic kidney disease (CKD) Methods Our database of AF patients diagnosed with HF and CKD from 2018 to 2023 was used to obtain laboratory, echocardiography, electrocardiogram (ECG), and clinical outcomes data. Inclusion criteria were all AF patients with HF and CKD using Apixaban. And we compared bleeding, systemic thrombotic events including stroke/systemic embolism and death according to off-label real -world dose of Apixaban. Results Among 370 AF patients with HF and CKD (78.4±9.7 years), 197 (53.2%) patients took off-label underdosed Apixaban. Difference in the baseline characteristics was not observed among patients including CHA2DS2 VASc score and HASBLED score. During the median 18-month follow-up, there was no significant difference of systemic thrombotic events including stroke/systemic embolism and death (P=0.705) in the off-label underdosed Apixaban group vs. those with standard dose or off-label overdosed Apixaban. And, there was also no significant difference of bleeding to off-label real-world dose of Apixaban (off-label underdose vs. standard dose, P=0.600; off-label overdose vs. standard dose, P=0.395; off-label underdose vs. off-label overdose, P=0.469). however, in multivariate analysis, CHA2DS2VASc score was independent risk factors for systemic thrombotic events (OR 1.994; CI 1.084-3.669; P=0.027). Conclusions There was no significant difference of systemic thrombotic events including stroke/systemic embolism and death in AF patients with no difference in the risk of bleeding in AF patients with HF and CKD, supporting the apixaban dosing tailored to specific clinical features and drug pharmacokinetics of the Asian patients.Kaplan-Meier Curve