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Efficacy and Safety of the Fixed-Dose Versus Variable-Dose of 4-PCC for Vitamin K Antagonist Reversal: A Comprehensive Systematic Review and Meta-Analysis

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Abstract

Background

The optimal dosing strategy of four-factor prothrombin complex concentrate (4F-PCC) for vitamin K antagonists (VKAs) reversal is unknown.

Methods

We conducted systematic search on the PubMed, SCOPUS, and Embase databases from inception to December 2020 for clinical studies that compared the fixed-dose versus variable-dose of 4-PCC for VKAs reversal with at least one reported clinical outcome. The treatment effects were expressed as relative ratios (RR) with 95% confidence intervals (CIs) and pooled by a random-effects model.

Results

Ten studies, including 988 patients, were included. Fixed-dose 4-PCC was associated with lower rate of mortality (RR= 0.65, 95% CI 0.47 to 0.9, p= 0.009), comparable rate of thromboembolic event (TEE) (RR= 1.10, 95%CI 0.44 to 2.80, p= 0.826), and lower goal INR reached (RR= 0.87, 95%CI 0.78 to 0.96, p= 0.007). Less 4-PCC cumulative dose, shorter duration of order-to-needle time, similar hospital length of stay, the comparable time required for INR reversal, higher post-4-PCC INR, and a higher need for additional dose were observed in fixed-dose.

Conclusions

The use of a fixed-dose of 4-PCC may be considered an effective and safe dosing strategy for VKAs reversal in various clinical situations. However, further well-designed, controlled studies should be conducted focusing on clinical outcomes to determine the optimal dose of 4-PCC for VKAs reversal.

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Data Availability

All data generated or analyzed during this study were included in the article.

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Acknowledgements

We would like to thank Dr. Jamal Rahmani for the appropriate conduction of systematic reviews and meta-analysis.

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Keyhan Mohammadi & Azita Hajhossein Talasaz

  2. Pharmacy Student, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Shakila Yaribash

  3. Division of Food Safety and Hygiene, Department of Environmental Health, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Mahmood Alizadeh Sani

  4. Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran

    Azita Hajhossein Talasaz

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  1. Keyhan Mohammadi
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Contributions

All authors were responsible for the study conception and design. KM, SY, and MA contributed to database searching, data extraction, assessment of study quality, data analysis and interpretation, and drafting of the manuscript. AT and KM critically evaluated and revised the manuscript. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Azita Hajhossein Talasaz.

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Mohammadi, K., Yaribash, S., Sani, M.A. et al. Efficacy and Safety of the Fixed-Dose Versus Variable-Dose of 4-PCC for Vitamin K Antagonist Reversal: A Comprehensive Systematic Review and Meta-Analysis. Cardiovasc Drugs Ther 36, 533–546 (2022). https://doi.org/10.1007/s10557-021-07192-0

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