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The Prediction Model of Warfarin Individual Maintenance Dose for Patients Undergoing Heart Valve Replacement, Based on the Back Propagation Neural Network

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Abstract

Background and Objective

Because of the narrow therapeutic window and huge inter-individual variation, the individual precision on anticoagulant therapy of warfarin is challenging. In our study, we aimed to construct a Back Propagation Neural Network (BPNN) model to predict the individual warfarin maintenance dose among Chinese patients who have undergone heart valve replacement, and validate its prediction accuracy.

Methods

In this study, we analyzed 13,639 eligible patients extracted from the Chinese Low Intensity Anticoagulant Therapy after Heart Valve Replacement database, which collected data on patients using warfarin after heart valve replacement from 15 centers all over China. Ten percent of patients who were finally enrolled in the database were used as the external validation, while the remaining were randomly divided into the training and internal validation groups at a ratio of 3:1. Input variables were selected by univariate analysis of the general linear model; 2.0, the mean value of the international normalized ratio (INR) range 1.5–2.5, was used as the mandatory variable. The BPNN model and the multiple linear regression (MLR) model were constructed by the training group and validated through comparisons of the mean absolute error (MAE), mean squared error (MSE), root mean squared error (RMSE), and ideal predicted percentage.

Results

Finally, 10 input variables were selected and a three-layer BPNN model was constructed. In the BPNN model, the value of MAE (0.688 mg/day and 0.740 mg/day in internal and external validation, respectively), MSE (0.580 mg/day and 0.599 mg/day in internal and external validation, respectively), and RMSE (0.761 mg/day and 0.774 mg/day in internal and external validation, respectively) were achieved. Ideal predicted percentages were high in both internal (63.0%) and external validation (59.7%), respectively. Compared with the MLR model, the BPNN model showed a higher ideal prediction percentage in the external validation group (59.7% vs. 56.6%), and showed the best prediction accuracy in the intermediate-dose subgroup (internal validation group: 85.2%; external validation group: 84.7%) and a high predicted percentage in the high-dose subgroup (internal validation group: 36.2%; external validation group: 39.8%), but poor performance in the low-dose subgroup (internal validation group: 0%; external validation group: 0.3%). Meanwhile, the BPNN model showed better ideal prediction percentage in the high-dose group than the MLR model (internal validation: 36.2% vs. 31.6%; external validation: 42.8% vs. 37.8%).

Conclusion

The BPNN model shows promise for predicting the warfarin maintenance dose after heart valve replacement.

Plain Language Summary

Because of the narrow therapeutic window and huge inter-individual variation, the individual precision on anticoagulant therapy of warfarin is still a challenge. According to the rapid development of artificial intelligence, our study was based on a clinical big database and used the advanced algorithm—Back Propagation Neural Network—to construct a prediction model of warfarin maintenance dose. It showed a high prediction accuracy of over 59%, and manifested obvious improvement of the prediction ability in the high-dose group. Hence, the BPNN model shows promise for predicting the precise individual therapy of warfarin.

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Acknowledgements

The authors appreciated the other members who provided their generous contributions during the study.

Author information

Authors and Affiliations

  1. Department of Evidence-Based Medicine and Clinical Epidemiology, West China Hospital, Sichuan University, Guo Xue Xiang 37#, Chengdu, 610041, Sichuan, China

    Qian Li & Jin Chen

  2. Department of Career Development Division, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, China

    Jing Wang

  3. Department of Hematology, West China Hospital, Sichuan University, Chengdu, China

    Huan Tao

  4. Department of Nutrition, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Qin Zhou

  5. Department of Anesthesiology, China Mianyang Central Hospital, Mianyang, China

    Jie Chen

  6. Department of Cardiovascular Surgery, Tianjin Central Hospital, Tianjin, China

    Bo Fu

  7. Department of Social Medicine and Health Management, Shandong University, Jinan, China

    WenZhe Qin

  8. Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, China

    Dong Li & JiangLong Hou

  9. Department of Research Laboratory for Human Reproduction, Faculty of Medicine and School of Public Health, Université Libre de Bruxelles (ULB), Brussels, Belgium

    Wei-hong Zhang

  10. International Centre for Reproductive Health (ICRH), Department of Public Health and Primary Care, Ghent University, Ghent, Belgium

    Wei-hong Zhang

Authors
  1. Qian Li
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  2. Jing Wang
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  8. Dong Li
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  10. Jin Chen
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  11. Wei-hong Zhang
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Contributions

QL and JW were co-first authors and were responsible for interpretation and analysis of the data, and drafting of the manuscript. HT and QZ were responsible for analysis of the data. JC and WQ were responsible for interpretation of the research. BF, JH and LD performed the conception work, and data acquisition. WHZ was responsible for revising the language for the content and verifying the design of the research. JC, as the corresponding author, was responsible for the conception and design of the research, and revising critically for important intellectual content. All authors approved the final version submitted for publication.

Corresponding author

Correspondence to Jin Chen.

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Funding

This project was supported by the National Natural Science Foundation (Project Numbers 71974137 and 81641021) and the National Science and Technology Pillar Program during the Twelfth Five-Year Plan Period (Project Number 2011BAI11B18). The funding sources have no role in the design, implementation, data analysis, and article writing, or in the decision to submit the article for publication.

Conflict of interest

Qian Li, Jing Wang, Huan Tao, Qin Zhou, Jie Chen, Bo Fu, WenZhe Qin, Dong Li, JiangLong Hou, Jin Chen, and Wei-hong Zhang declare that they have no conflicts of interests.

Ethics approval

All methods and study protocols have been approved by the Ethics Committee of West China Hospital of Sichuan University (ChiECRCT-201792). As this was a retrospective study, as per the ethical approval documents.

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Informed consent has been exempted.

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Li, Q., Wang, J., Tao, H. et al. The Prediction Model of Warfarin Individual Maintenance Dose for Patients Undergoing Heart Valve Replacement, Based on the Back Propagation Neural Network. Clin Drug Investig 40, 41–53 (2020). https://doi.org/10.1007/s40261-019-00850-0

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