Real-World Comparative Study of Ultra-Low-Dose Rivaroxaban in Very Elderly Patients with Atrial Fibrillation

Dan Han,1 Qian Ni,2 Jialin Qi,2 Huanyu Ni,1 Baoyan Wang1 1Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 2Department of pharmacy, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Baoyan Wang, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Tel +86-15161477178, Email [email protected]: Optimal dosing of rivaroxaban in very elderly (≥ 80 years) nonvalvular atrial fibrillation (AF) patients remains debated, particularly concerning ultra-low-dose (5 mg daily) regimens derived from clinician judgement. This study aimed to describe real-world comparative outcomes associated with these clinician-selected dosing regimens.Methods: The study included 1389 very elderly nonvalvular AF patients (≥ 80 years) who received rivaroxaban between January 2018 and December 2022, with 373, 604, and 412 patients receiving 5 mg, 10 mg, and 15/20 mg daily, respectively. Baseline characteristics were balanced using stabilized inverse probability of treatment weighting (IPTW). The outcomes included composite efficacy outcomes (stroke, systemic embolism, myocardial infarction and cardiovascular death) and major bleeding. Subgroup analysis and plasma trough level comparisons were conducted to further assess consistency and pharmacokinetics.Results: The composite efficacy event rates were 9.3%, 6.6%, and 7.0% for the 5 mg, 10 mg, and 15/20 mg groups, respectively. After IPTW, there was no statistically significant difference in composite efficacy outcomes between three groups (HR for 10 mg vs 5 mg: 0.71, 95% CI: 0.44– 1.15; HR for 15/20 mg vs 5 mg: 0.91, 95% CI: 0.52– 1.59). However, major bleeding occurred in 1.6%, 3.6%, and 6.1% of patients, exhibited a dose-dependent increase. The 15/20 mg group had a 4.27-fold higher risk compared to the 5 mg group (HR: 4.27, 95% CI: 1.66– 10.97), while the 10 mg group showed no significant elevation (HR: 2.11, 95% CI: 0.82– 5.40). Subgroup analysis confirmed consistent efficacy and safety trends across specified subgroups. Plasma trough concentrations were significantly higher in the 15/20 mg group compared to the 5 mg group, with no significant difference between the 10 mg and 5 mg groups.Conclusion: In very elderly AF patients, ultra-low-dose rivaroxaban (5 mg daily) provided comparable efficacy to higher doses while significantly reducing major bleeding. This regimen may be a balanced option for high-risk elderly populations. Keywords: atrial fibrillation, very elderly patients, rivaroxaban, ultra-low-dose