Stroke Prevention With Direct Oral Anticoagulants (Doac) Versus Warfarin In Patients With Non-Valvular Atrial Fibrillation (Nvaf): A Real-World Cohort Meta-Analysis

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Rizqiana Arum Sari
Habib Laksmana Prima
Delta Iswara
Faishal Hanif

Abstract

Atrial fibrillation, particularly NVAF, is a major risk factor for stroke and systemic embolism, yet real-world evidence on the effectiveness and safety of DOACs versus warfarin remains limited. This systematic review and meta-analysis compared the effectiveness and safety outcomes of direct oral anticoagulants (DOACs) vs for stroke prevention in patients with NVAF. This review followed PRISMA guidelines. Cohort studies published in the past 10 years were identified from PubMed, Scopus, and Google Scholar, with study quality assessed using the Newcastle–Ottawa Scale. Pooled hazard ratios for the effectiveness and safety of DOACs versus warfarin in NVAF were calculated using a random-effects model in RevMan 5.4.1. A total of 12 studies were included in this meta-analysis. Compared with warfarin, DOACs significantly reduced the risk of stroke or systemic embolism (HR = 0.76, 95% CI: 0.67–0.87), ischemic stroke (HR = 0.70, 95% CI: 0.54–0.92), and hemorrhagic stroke (HR = 0.62, 95% CI: 0.45–0.86). All-cause mortality was numerically lower with DOACs but not statistically significant (HR = 0.82, 95% CI: 0.66–1.01). For safety outcomes, DOACs were associated with a lower risk of major bleeding (HR = 0.81, 95% CI: 0.65–1.00) and intracranial hemorrhage (HR = 0.57, 95% CI: 0.50–0.65), while gastrointestinal bleeding did not differ significantly between groups (HR = 1.09, 95% CI: 0.62–1.90). Based on real-world cohort evidence, DOACs demonstrate superior effectiveness in reducing stroke and systemic embolism and a more favorable safety profile compared with warfarin in patients with NVAF.

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How to Cite
Sari, R. A., Prima, H. L. ., Iswara, D., & Hanif , F. . (2026). Stroke Prevention With Direct Oral Anticoagulants (Doac) Versus Warfarin In Patients With Non-Valvular Atrial Fibrillation (Nvaf): A Real-World Cohort Meta-Analysis. International Journal of Health Engineering and Technology, 5(2). https://doi.org/10.55227/ijhet.v5i2.995
Section
Health

References

Alberts, M., Chen, Y. W., Lin, J. H., Kogan, E., Twyman, K., & Milentijevic, D. (2020). Risks of stroke and mortality in atrial fibrillation patients treated with rivaroxaban and warfarin. Stroke, 51(2), 549–555.

Al-Maawali, M. S., Al-Naamani, H. H., Mokadem, L. N., Al-Maawali, G., Salman, B., & Al-Zakwani, I. (2022). Comparative effectiveness and safety of rivaroxaban and warfarin for stroke prevention in patients with non-valvular atrial fibrillation in an Omani tertiary care hospital. The Open Cardiovascular Medicine Journal, 16, e187419242202281. https://doi.org/10.2174/18741924-v16-e2202281

Amin, A., Keshishian, A., Trocio, J., Dina, O., Le, H., Rosenblatt, L., & Liu, X. (2017). Risk of stroke/systemic embolism, major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban, dabigatran or rivaroxaban compared with warfarin in the United States Medicare population. Current Medical Research and Opinion, 33(9), 1595–1604.

Avezum, A., Lopes, R. D., Schulte, P. J., Lanas, F., Gersh, B. J., Hanna, M., Pais, P., Erol, C., Diaz, R., Bahit, M. C., Bartunek, J., De Caterina, R., Goto, S., Ruzyllo, W., Zhu, J., Granger, C. B., & Alexander, J. H. (2015). Apixaban in comparison with warfarin in patients with atrial fibrillation and valvular heart disease: findings from the ARISTOTLE trial. Circulation, 132, 624–632.

Bang, O. Y., On, Y. K., Lee, M.-Y., Jang, S.-W., Han, S., Han, S., Won, M.-M., Park, Y.-J., Lee, J.-M., & Choi, H.-Y. (2020). The risk of stroke/systemic embolism and major bleeding in Asian patients with non-valvular atrial fibrillation treated with non-vitamin K oral anticoagulants compared to warfarin: Results from a real-world data analysis. PLoS One, 15(11), e0242922.

Bradley, M., Welch, E. C., Eworuke, E., Graham, D. J., Zhang, R., & Huang, T.-Y. (2020). Risk of stroke and bleeding in atrial fibrillation treated with apixaban compared with warfarin. Journal of General Internal Medicine, 35(12), 3597–3604. https://doi.org/10.1007/s11606-020-06180-8

Chen, A., Stecker, E. C., & Warden, B. A. (2020). Direct oral anticoagulant use: A practical guide to common clinical challenges. Journal of the American Heart Association, 9(13), e017559.

Coleman, C. I., Antz, M., Bowrin, K., Evers, T., Simard, E. P., Bonnemeier, H., & Cappato, R. (2016). Real-world evidence of stroke prevention in patients with nonvalvular atrial fibrillation in the United States: the REVISIT-US study. Current Medical Research and Opinion. https://doi.org/10.1080/03007995.2016.1237937

de Lusignan, S., Hobbs, F. D. R., Liyanage, H., Sherlock, J., Ferreira, F., Tripathy, M., Heiss, C., Feher, M., & Joy, M. P. (2022). Long term follow up of direct oral anticoagulants and warfarin therapy on stroke, with all-cause mortality as a competing risk, in people with atrial fibrillation: Sentinel network database study. PLOS ONE, 17(9), e0265998. https://doi.org/10.1371/journal.pone.0265998

El Moussa, S., Al Yasari, A., Abdelfattah, A., Shasna, T. D. F., Ahmed, A. I. H., Al-Jarrad, A. T. A. K., Pemmasani, L. T., Abid, M., & Khalid, S. (2025). Systematic review: efficacy and safety of direct oral anticoagulants (DOACs) versus warfarin in atrial fibrillation. Fortune Journal of Health Sciences.

Forslund, T., Wettermark, B., Andersen, M., & Hjemdahl, P. (2018). Stroke and bleeding with non-vitamin K antagonist oral anticoagulant or warfarin treatment in patients with non-valvular atrial fibrillation: a population-based cohort study. Europace, 20(3), 420–428. https://doi.org/10.1093/europace/euw416

Gieling, E. M., van den Ham, H. A., van Onzenoort, H., Bos, J., Kramers, C., de Boer, A., de Vries, F., & Burden, A. M. (2017). Risk of major bleeding and stroke associated with the use of vitamin K antagonists, nonvitamin K antagonist oral anticoagulants and aspirin in patients with atrial fibrillation: a cohort study. British Journal of Clinical Pharmacology, 83(8), 1844–1859.

January, C. T., Wann, L. S., Calkins, H., Chen, L. Y., Cigarroa, J. E., Cleveland, J. C., Ellinor, P. T., Ezekowitz, M. D., Field, M. E., Furie, K. L., Heidenreich, P. A., Murray, K. T., Shea, J. B., Tracy, C. M., & Yancy, C. W. (2019). 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. Circulation, 140(2), e125–e151.

Joglar, J. A., Chung, M. K., Armbruster, A. L., Benjamin, E. J., Chyou, J. Y., Cronin, E. M., & Deswal, A. (2024). 2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Journal of the American College of Cardiology, 83(1), 109–279.

Lee, H., Hong, J. H., & Seo, K.-D. (2023). Long-term stroke and major bleeding risk in patients with non-valvular atrial fibrillation: A comparative analysis between non-vitamin K antagonist oral anticoagulants and warfarin using a clinical data warehouse. Frontiers in Neurology, 14, 1058781. https://doi.org/10.3389/fneur.2023.1058781

Lee, J. J., Ha, A. C. T., Dorian, P., Verma, M., Goodman, S. G., & Friedrich, J. O. (2020). Meta-analysis of safety and efficacy of direct oral anticoagulants versus warfarin according to time in therapeutic range in atrial fibrillation. American Journal of Cardiovascular Drugs.

Li, W.-H., Huang, D., Chiang, C.-E., Lau, C.-P., Tse, H.-F., Chan, E. W., Wong, I. C. K., Lip, G. Y. H., Chan, P.-H., & Siu, C.-W. (2017). Efficacy and safety of dabigatran, rivaroxaban, and warfarin for stroke prevention in Chinese patients with atrial fibrillation: the Hong Kong Atrial Fibrillation Project. Clinical Cardiology, 40(4), 222–229. https://doi.org/10.1002/clc.22649

Milentijevic, D., Lin, J. H., Connolly, N., Chen, Y.-W., Kogan, E., Shrivastava, S., Sjoeland, E., & Alberts, M. J. (2021). Risk of stroke outcomes in atrial fibrillation patients treated with rivaroxaban and warfarin. Journal of Stroke and Cerebrovascular Diseases, 30(5), 105715. https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.105715

Paschke, L. M., Klimke, K., Altiner, A., von Stillfried, D., & Schulz, M. (2020). Comparing stroke prevention therapy of direct oral anticoagulants and vitamin K antagonists in patients with atrial fibrillation: a nationwide retrospective observational study. BMC Medicine, 18, 254.

Powell, E. M., Gungabissoon, U., Tazare, J., Smeeth, L., Baptiste, P. J., Bin Hammad, T. M., Wong, A. Y. S., Douglas, I. J., & Wing, K. (2024). Comparison of oral anticoagulants for stroke prevention in atrial fibrillation using the UK Clinical Practice Research Datalink Aurum: A reference trial (ARISTOTLE) emulation study. PLOS Medicine, 21(8), e1004377. https://doi.org/10.1371/journal.pmed.1004377

Ramagopalan, S. V, Sicras-Mainar, A., Polanco-Sanchez, C., Carroll, R., & de Bobadilla, J. F. (2019). Patient characteristics and stroke and bleeding events in nonvalvular atrial fibrillation patients treated with apixaban and vitamin K antagonists: a Spanish real-world study. Journal of Comparative Effectiveness Research, 8(14), 1201–1212.

Scridon, A., & Balan, A. I. (2023). Challenges of anticoagulant therapy in atrial fibrillation – focus on gastrointestinal bleeding. International Journal of Molecular Sciences, 24(8), 6879.

Song, Y., Chen, J., Zhang, Y., & Zhang, Q. (2025). Prevalence and Risk Factors of Stroke in Patients with Nonvalvular Atrial Fibrillation: A Case-Control Study. World Neurosurgery, 195, 123652.

Wang, C.-L., Wu, V. C.-C., Huang, Y.-T., Kuo, C.-F., Chu, P.-H., Chen, Y.-L., Wen, M.-S., & Chang, S.-H. (2019). Safety and effectiveness of non–vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation and anemia: a retrospective cohort study. Journal of the American Heart Association, 8, e012029.

Yap, L. Bin, Eng, D. T. S., Sivalingam, L., Rusani, B. I., Umadevan, D., Muhammad, Z., Koh, K. W., Aisha, B., Hashim, M. I., Rebo, R., Hussin, A., Kaur, S., Shanmugam, R., & Omar, R. (2016). A comparison of dabigatran with warfarin for stroke prevention in atrial fibrillation in an Asian population. Clinical and Applied Thrombosis/Hemostasis, 22(8), 792–797. https://doi.org/10.1177/1076029615584664