Fixed dose versus 3-day loading dose warfarin initiation in atrial fibrillation: effects on INR stabilization and...

Warfarin initiation strategies vary, with some clinicians using either a fixed-dose or loading-dose regimen to achieve therapeutic anticoagulation. However, evidence comparing their effectiveness in multiethnic Asian populations without genotype-guided dosing remains limited.

To compare a fixed-dose regimen with a 3-day loading-dose regimen in terms of international normalized ratio (INR) stability and time in the therapeutic range (TTR) over 12 months in a multiethnic atrial fibrillation (AF) cohort. We also aimed to evaluate the relationship between the time to initial INR stabilization and the subsequent anticoagulation quality.

This multicenter, retrospective cohort study included 780 warfarin-naïve patients with AF from two tertiary hospitals (2010 to 2022). Patients were grouped by the initiation strategy: fixed-dose (n = 501) or 3-day loading-dose (n = 279). The primary outcome was the TTR at 3, 6, and 12 months. The association between time to INR stabilization and TTR was assessed using Spearman's correlation, and a General Linear Model (GLM) was used to adjust for comprehensive demographic and clinical confounders.

The time to initial INR stabilization showed a strong inverse correlation with TTR across all time points (Spearman's r = -0.600 to -0.710; p < 0.001). Although the unadjusted analysis suggested that the INR stabilized faster in the loading-dose group (mean: 111.8 vs. 138.6 days; p < 0.001), this difference became insignificant after accounting for confounding factors (adjusted mean: 94.1 vs 104.1 days; p = 0.248). Similarly, adjusted means of TTRs did not differ significantly between regimens at 3, 6, or 12 months.

The choice between fixed-dose and loading-dose warfarin initiation strategies does not independently influence long-term anticoagulation control. Instead, time to initial INR stabilization is the strongest predictor of TTR quality over 12 months. Clinical efforts should prioritize early and intensive INR monitoring in settings without genotype-guided dosing, as both baseline characteristics and the ongoing clinical management likely determine anticoagulation outcomes.