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 to warfarin in atrial fibrillation (AF) patients. 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 AF patients. Primary outcomes included changes in coronary plaque volumes (PV). Mean differences 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 mm3; 95% CI: -12.99 to -1.14; p=0.02; I2=0%) and fibrous PV (MD -12.52 mm3; 95% CI: -24.92 to -0.12; p=0.05; I2=0%) compared to warfarin. No significant differences were observed in total PV, non-calcified 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 endpoints. DOACs significantly reduce progression of calcified and fibrous plaque volumes compared to warfarin in AF patients. 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.
Keywords: Atrial fibrillation; DOAC; meta-analysis; plaque.
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