Comparison of Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban in Patients With Valvular Atrial Fibrillation: A Network Meta-Analysis of Randomized-Control Trials and Observational Studies

Abstract

The objective of this network meta-analysis was to assess the efficacy and safety of apixaban, dabigatran, rivaroxaban, and edoxaban in patients diagnosed with atrial fibrillation and valvular heart disease. A comprehensive search was conducted across various electronic databases, including PubMed, Embase, and Web of Science, from inception to February 15, 2024. The search strategy utilized a combination of medical subject headings (MeSH) terms and relevant keywords related to valvular heart disease, atrial fibrillation, anticoagulant therapy, and study design, such as randomized controlled trials and observational studies. The outcomes evaluated in this analysis comprised the incidence of stroke or systemic embolism (SE), as well as the occurrences of major bleeding events. A total of 10 studies were incorporated into this meta-analysis, encompassing 40,662 participants. Of these, 12,385 received apixaban, 2,829 received dabigatran, 13,662 received rivaroxaban, 2,582 received edoxaban, and 9,202 received warfarin. The duration of follow-up in the included studies ranged from 3 to 54 months. Among the four direct oral anticoagulants (DOACs) studied, apixaban demonstrated a significant reduction in the risk of stroke or SE when compared to other DOACs and warfarin, highlighting its efficacy in patients with atrial fibrillation and valvular heart disease. Additionally, apixaban exhibited a lower risk of major bleeding events, further emphasizing its favorable safety profile compared to the other agents assessed. In conclusion, our findings suggest that apixaban may be more effective and safer than other DOACs and warfarin in this patient population. However, additional studies are warranted to compare the various DOACs in this cohort to identify the optimal treatment strategy for preventing adverse outcomes.

Keywords: apixaban; dabigartan; rivaroxaban; systematic review and meta-analysis; valvular atrial fibrillation.

Figure 1. PRISMA flowchart of study selection

Figure 2. Risk of bias assessment of included studies

Figure 3. Comparison of DOACs versus Warfarain in the prevention of stroke and SE

RR: Risk ratio; CI: Confidence interval Sources: References [12-21]

Figure 4. Comparison of major bleeding events between different DOACs and warfarin

RR: Risk ratio; CI: Confidence interval Sources: References [12-21]

Figure 5. Below the diagonal, in yellow, are the relative risks (RRs) from network meta-analyses concerning stroke or systemic embolism, while above the diagonal, in green, are the RRs for major bleeding for all pairwise comparisons. Significant findings are highlighted in bold. To derive RRs for comparisons in the opposite direction, reciprocals must be calculated.

All values are presented as relative risk (95% confidence interval)