Comparative Effectiveness of Novel Anticoagulants versus Warfarin in Patients with Atrial Fibrillation

Abstract

Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with a substantially increased risk of ischemic stroke and systemic embolism. Although warfarin has long been the standard oral anticoagulant for stroke prevention, its clinical use is limited by the need for regular monitoring, numerous drug and food interactions, and variable anticoagulant effects. Novel oral anticoagulants (NOACs) have emerged as effective alternatives with more predictable pharmacological profiles and improved safety. This study aimed to compare the effectiveness and safety of NOACs with warfarin in patients with non-valvular atrial fibrillation (NVAF).

Methodology: A retrospective comparative cohort study was conducted involving 400 patients with non-valvular atrial fibrillation, including 200 patients treated with NOACs and 200 treated with warfarin. Data were extracted from hospital medical records for patients managed between January 2021 and December 2024. The primary effectiveness outcome was a composite of ischemic stroke or systemic embolism, while the primary safety outcome was major bleeding. Continuous variables were compared using the independent-samples t-test, and categorical variables were analyzed using the Chi-square test. Time-to-event outcomes were evaluated using Kaplan–Meier survival analysis with comparisons performed using the log-rank test. Multivariable Cox proportional hazards regression analysis was used to identify independent predictors of clinical outcomes and estimate hazard ratios (HRs) with 95% confidence intervals (CIs). A two-tailed p-value < 0.05 was considered statistically significant.

Results: Patients receiving NOACs had significantly lower rates of ischemic stroke or systemic embolism than those receiving warfarin (5.0% vs. 12.0%; p = 0.012). Major bleeding was also significantly less frequent in the NOAC group (6.0% vs. 14.0%; p = 0.007). Furthermore, NOAC therapy was associated with significantly lower rates of intracranial hemorrhage, all-cause mortality, and hospitalization. Kaplan–Meier analysis demonstrated significantly higher event-free survival among patients receiving NOACs (log-rank p = 0.005). After adjustment for potential confounders, multivariable Cox regression analysis showed that NOAC therapy independently reduced the risk of adverse clinical outcomes compared with warfarin (HR = 0.48; 95% CI: 0.24–0.92; p = 0.028).

Conclusion: Compared with warfarin, NOACs demonstrated superior effectiveness and safety in patients with non-valvular atrial fibrillation. Their use was associated with significantly lower risks of thromboembolic events, major bleeding, intracranial hemorrhage, all-cause mortality, and hospitalization, supporting current recommendations that favor NOACs as the preferred oral anticoagulant therapy for most patients with non-valvular atrial fibrillation.