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Meta-Analysis
. 2025 Dec;39(6):1375-1386.
doi: 10.1007/s10557-024-07616-7. Epub 2024 Aug 17.

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants Compared with Vitamin K Antagonists in Patients with Atrial Fibrillation and Type 2 Valvular Heart Disease: A Systematic Review and Meta-Analysis

Xiaoyun Liang #  1 , Shangyu Liu #  1 , Lishuang Ji  1 , Fangfang Ma  1 , Guoyuan Song  1 , Fang Li  1 , Gang Liu  2   3   4   5   6
Affiliations
Meta-Analysis

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants Compared with Vitamin K Antagonists in Patients with Atrial Fibrillation and Type 2 Valvular Heart Disease: A Systematic Review and Meta-Analysis

Xiaoyun Liang et al. Cardiovasc Drugs Ther. 2025 Dec.

Abstract

Purpose: This meta-analysis aimed to evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and type 2 valvular heart disease (VHD).

Methods: We searched the PubMed, LILACS, and MEDLINE databases to retrieve, randomized controlled trials (RCTs) comparing NOACs and VKAs in patients with AF and type 2 VHD, excluding mitral stenosis (moderate to severe, of rheumatic origin) or mechanical heart valves. The efficacy outcomes assessed were stroke and systemic embolism (SE), while safety outcomes included major bleeding and intracranial hemorrhage (ICH).

Results: Seven RCTs, including 16,070 patients with AF and type 2 VHD, were included. NOACs reduced the risk of stroke/SE (relative risk [RR], 0.75; 95% confidence interval [CI], 0.64-0.89; P = 0.0005), with no significant difference in major bleeding (RR, 0.88; 95% CI, 0.64-1.21; P = 0.43). The risk of ICH was reduced with NOACs (RR, 0.46; 95% CI, 0.27-0.77; P = 0.003). For patients with AF and bioprosthetic heart valve (five trials, 2805 patients), stroke/SE risks (RR, 0.65, 95% CI, 0.44-0.96) with NOACs were superior to VKAs. Major bleeding risks without ENVISAGE TAVI AF trial (RR, 0.53; 95% CI, 0.30-0.94; P = 0.03) with NOACs were superior to VKAs. The risks of ICH (RR, 0.61; 95% CI 0.34-1.09; P = 0.09) with NOACs were comparable to VKAs.

Conclusions: NOACs demonstrate efficacy and safety in patients with AF and type 2 VHD and reduce the risk of stroke/SE and ICH when compared with those with VKAs.

Keywords: Anticoagulation therapy; Atrial fibrillation; Non-vitamin K antagonist; Oral anticoagulants; Valvular heart disease; Vitamin K antagonists.

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Conflict of interest statement

Declarations. Ethics Approval: This study used a meta-analysis approach with data derived from previously published studies that were systematically statistically integrated and analyzed. No ethical review or informed consent was required for this study. Consent to Participate: The data involved had been publicly released and did not involve direct intervention or collection of personal information from new participants. Consent for Publication: All participants should appear in the manuscript. Conflict of Interest: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram for the study search process
Fig. 2
Fig. 2
The forest plot illustrates the individual and pooled estimates of the risks associated with stroke/systemic embolism, major bleeding, and intracranial hemorrhage in patients with atrial fibrillation and type 2 valvular heart disease on anticoagulation. CI confidence interval, M–H Mantel–Haenszel, NOACs new oral anticoagulants, VKAs vitamin K antagonists; the asterisks indicate that the DAWA pilot study conducted by Rodrigues Duraes et al. (2016) only reported bleeding in the warfarin and dabigatran groups, and no reports of major bleeding and intracranial hemorrhage in the warfarin and dabigatran groups were reported, so they were not included in this analysis
Fig. 3
Fig. 3
The forest plot illustrates the individual and pooled estimates of the risks associated with stroke/systemic embolism, major bleeding, and intracranial hemorrhage in patients with atrial fibrillation and bioprosthetic heart valves on anticoagulation. CI confidence interval, M–H Mantel–Haenszel, NOACs new oral anticoagulants, VKAs vitamin K antagonists
Fig. 4
Fig. 4
The forest plot illustrates the sensitivity analysis excluding the ENVISAGE-TAVI AF trial of the risks associated with major bleeding in patients with atrial fibrillation and bioprosthetic heart valves on anticoagulation. CI confidence interval, M–H Mantel–Haenszel, NOACs new oral anticoagulants, VKAs vitamin K antagonists
See this image and copyright information in PMC

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