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Efficacy and Safety of Direct Oral Anticoagulants (DOACs) Versus Warfarin in Atrial Fibrillation Patients with Prior Stroke: a Systematic Review and Meta-analysis

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Abstract

Background

The purpose of this meta-analysis was to compare efficacy and safety of direct oral anticoagulants (DOACs) to warfarin for secondary stroke prevention among adult patients with atrial fibrillation and prior stroke.

Methods

Major repositories were screened for randomized controlled trials (RCTs), RCT subgroups, and observational studies (OBSs, divided in claims and non-claims). Occurrences of ischemic stroke or transient ischemic attack, systemic embolism, all-cause mortality, intracranial hemorrhage (ICH), and major bleeding were outcomes of interest. Hazard ratios (HRs) and their confidence intervals (95%CIs) were pooled using random-effects models for each study design. Claims studies were analyzed separately from non-claims, while RCT subgroups were grouped with OBSs (non-claims) as the randomization was broken.

Results

Of 8647 articles, 20 were included (one RCT, six RCT subgroups, nine claims, and four non-claims). Comparing DOACs to warfarin, pooled HRs (95%CI) were consistently in favor of DOACs although some did not reach statistical significance: for ischemic stroke, 0.84 (0.66–1.07) in claims; 0.90 (0.77–1.06) in non-claims and RCT subgroups; for systemic embolism, 0.77 (0.62–0.96) in claims; 0.86 (0.77–0.96) in non-claims and RCT subgroups; for all-cause mortality, 0.57 (0.33–0.99) in claims; 0.87 (0.79–0.96) in non-claims and RCT subgroups; for ICH, 0.72 (0.39–1.33) in claims; 0.51 (0.38–0.67) in non-claims and RCT subgroups; and for major bleeding, 0.86 (0.71–1.03) in claims; 0.90 (0.76–1.08) for non-claims and RCT subgroups.

Conclusion

DOACs were associated with better efficacy and safety profiles than warfarin in atrial fibrillation patients with prior stroke, more specifically a lower risk of systemic embolism, all-cause mortality, and ICH.

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Availability of Data and Material

Not applicable. The data that were used for the present study were secondary data extracted from previously published papers that are herein referenced; data are available upon request to the corresponding author.

Code Availability

Not applicable.

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Authors and Affiliations

  1. School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences (MCPHS) University, Boston, MA, USA

    Kandavadivu Umashankar, Ebtissam Badawoud, Yuzhi Tang, Mengqi Zhou, Mattia Migliore & Rania A. Mekary

  2. Neurosurgery Unit, Santa Croce e Carle Hospital, Cuneo, Italy

    Marco Mammi

  3. Computational Neuroscience Outcomes Center, Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Marco Mammi & Rania A. Mekary

  4. Division of Cardiology, Department of Internal Medicine, Texas Tech University Health Sciences Center (TTUHSC), Paul L. Foster School of Medicine, El Paso, TX, USA

    Jorge C. Borges

  5. Portiuncula University Hospital and National University of Ireland Galway (NUIG), Galway, Ireland

    Aaron Liew

  6. Research Faculty, Harvard Medical School, Brigham and Women’s Hospital (CNOC), 179 Longwood Avenue, Boston, MA, 02115, USA

    Rania A. Mekary

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Contributions

JB, MMi, and RM conceived and designed the study. KU, EB, YT, and MZ collected the data. KU and RM performed the analyses. KU and MMa wrote the paper. RM edited the entire manuscript.

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Correspondence to Rania A. Mekary.

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Umashankar, K., Mammi, M., Badawoud, E. et al. Efficacy and Safety of Direct Oral Anticoagulants (DOACs) Versus Warfarin in Atrial Fibrillation Patients with Prior Stroke: a Systematic Review and Meta-analysis. Cardiovasc Drugs Ther 37, 1225–1237 (2023). https://doi.org/10.1007/s10557-022-07336-w

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