Direct Oral Anticoagulants Versus Warfarin on Coronary Plaque in Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials

ABSTRACT: Warfarin inhibits vitamin K-dependent proteins that prevent vascular calcification. We hypothesized that direct oral anticoagulants (DOACs), which do not interact with vitamin K, would slow coronary plaque progression compared with warfarin in patients with atrial fibrillation (AF). Following PRISMA guidelines and a prospectively registered protocol (PROSPERO: CRD420251026977), we systematically searched PubMed, Embase, and Cochrane databases through April 2025 for randomized controlled trials comparing DOACs with warfarin in patients with AF. Primary outcomes included changes in coronary plaque volumes (PV). Mean differences (MD) were calculated using Mantel-Haenszel method, with trial sequential analysis performed for all outcomes. Three RCTs with 272 patients (136 receiving DOACs) were included. Patients receiving DOACs showed significantly slower progression of calcified PV (MD -7.07 mm 3 ; 95% CI: -12.99 to -1.14; P = 0.02; I 2 = 0%) and fibrous PV (MD -12.52 mm 3 ; 95% CI: -24.92 to -0.12; P = 0.05; I 2 = 0%) compared with patients receiving warfarin. No significant differences were observed in total PV, noncalcified PV, fibro-fatty PV, or low attenuation PV. Trial sequential analysis indicated that 391 patients would be necessary for definitive conclusions regarding calcified PV. Risk of bias assessment indicated some concerns for all studies, with moderate certainty of evidence for most end points. DOACs significantly reduce progression of calcified and fibrous PV compared with warfarin in patients with AF. These findings suggest DOACs may promote more stable plaque composition, potentially reducing cardiovascular event risk. However, larger studies with longer follow-up are needed to confirm these results.