Arga Setyo Adji, Ade Meidian Ambari, Meilisa Purnama Dewi, Derren Rampengan, Setya Haksama, Evan Ricardo, Muhammad Reva Aditya, Ammar Nojaid, Michael Owen Hogipranata, Muhammad Iqhrammullah, Starry Rampengan, Fachrizal Ria Qhabibi, Bambang Edi Suwito
Background. Atrial fibrillation (AF) is a common cardiac arrhythmia, with ischemic stroke representing one of its most serious complications. Oral anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) is essential for stroke prevention in patients with AF. Objectives. This systematic review and meta-analysis aimed to compare the efficacy and safety of DOACs versus VKAs in reducing stroke risk and AF-related complications. Methods. We systematically searched PubMed, Europe PMC, Google Scholar, and Scopus for randomized controlled trials and non-randomized studies published up to February 2025 that compared DOACs with VKAs in patients with AF. Outcomes of interest included stroke, all-cause mortality, major bleeding, and intracranial hemorrhage. Random-effects models were used to calculate pooled estimates expressed as hazard ratios or relative risks, with corresponding p-values. Results. Twenty-two studies comprising 91,861 participants were included. DOAC therapy was associated with a significant reduction in stroke risk compared with VKAs (RR=0.53, p=0.020). Among individual DOACs, apixaban (p=0.010) and dabigatran (p=0.008) significantly reduced stroke and systemic embolic events, whereas rivaroxaban showed a marginal benefit (p=0.001). All-cause mortality was significantly reduced with dabigatran (p=0.010) and apixaban (p=0.050), but not with rivaroxaban (p=0.160). Apixaban demonstrated the lowest risk of major bleeding (p < 0.001), followed by dabigatran (p=0.010), while rivaroxaban did not show a significant reduction (p=0.400). Both dabigatran and apixaban significantly reduced the risk of intracranial hemorrhage (p < 0.001), whereas rivaroxaban did not (p=0.550). Conclusion. DOACs, particularly apixaban and dabigatran, demonstrated superior efficacy and safety compared with VKAs in reducing stroke, mortality, and bleeding risk in patients with AF. Rivaroxaban showed more limited benefit. © 2025, Amaltea Medical Publishing House. All rights reserved.
Medical Doctor Program, Faculty of Medicine, Hang Tuah University, Surabaya, Indonesia; Department of Health Policy and Administration, Universitas Airlangga, Surabaya, Indonesia; Department of Cardiology and Vascular Medicine, Universitas Indonesia, Jakarta, Indonesia; Medical Doctor Program, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia; Medical Doctor Program, Faculty of Medicine, Widya Mandala University, Surabaya, Indonesia; Medical Doctor Program, Faculty of Medicine, Brawijaya University, Malang, Indonesia; Postgraduate Program of Public Health, Universitas Muhammadiyah Aceh, Banda Aceh, Indonesia; Department of Cardiology and Vascular Medicine, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia; Department of Cardiology and Vascular Medicine, R.D. Kandou Central General Hospital, Manado, Indonesia; National Cardiovascular Center Harapan Kita, Jakarta, Indonesia; Department of Anatomy and Histology, Universitas Nahdlatul Ulama Surabaya, Surabaya, Indonesia
