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Efficacy and Safety of Clinically Driven Low-Dose Treatment with Direct Oral Anticoagulants in Asians with Atrial Fibrillation: a Systematic Review and Meta-analysis

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Abstract

Purpose

Although clinically driven low-dose (CDLD) treatment with direct oral anticoagulants (DOACs) is frequently administered to Asian patients with atrial fibrillation, clinical evidence confirming its efficacy remains insufficient. We evaluated the clinical efficacy and safety of CDLD treatment with DOACs compared to on-label dose treatment in Asian patients with atrial fibrillation and assessed the differences in the baseline characteristics between patients receiving these treatments.

Methods

We searched the MEDLINE, CENTRAL, EMBASE, Web of Science, and Scopus databases for articles from inception through July 2020.

Results

Thirteen studies were included in this meta-analysis. The baseline characteristics of the CDLD group were significantly different from those of the standard dose (STD) and standard low-dose (SLD) groups. The incidences of thromboembolic events (risk ratio [RR] 0.46, 95% confidence interval [CI] 0.29–0.73, p < 0.001) and major bleeding (RR 0.55, 95% CI 0.35–0.87, p = 0.01) in the CDLD group were lower than those in the SLD group; however, they were comparable with those in the STD group. The incidence of a composite endpoint in the CDLD group was not significantly different from that in the STD group but was significantly lower than that in the SLD group (RR 0.50, 95% CI 0.38–0.65, p < 0.001).

Conclusion

The clinical outcomes of CDLD treatment showed no difference compared to those of the STD treatment despite the vulnerable baseline characteristics of the CDLD group for thromboembolic and major bleeding events.

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Data Availability

All data generated or analyzed during this study are included in this published article (and its Supplementary Information files).

Code Availability

The Cochrane systematic review software Review Manager (RevMan® version 5.3, The Cochrane Collaboration, Oxford, United Kingdom)

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Funding

This work was supported by the 2019 Yeungnam University Research Grant (No. 219A580084). The supporter had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Author notes

  1. Jillie Choi and Jae Eun No contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon, 21983, Republic of Korea

    Jillie Choi, Jae Eun No & Yun Mi Yu

  2. Graduate Program of Industrial Pharmaceutical Science, Yonsei University, Incheon, Republic of Korea

    Jillie Choi, Jae Eun No & Yun Mi Yu

  3. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea

    Ju-Yeun Lee

  4. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Korea University, Sejong, Republic of Korea

    Soo An Choi

  5. Department of Internal Medicine, Seoul National University Boramae Medical Center and College of Medicine, Seoul National University, Seoul, Republic of Korea

    Woo-Young Chung

  6. College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongsangbuk-do, 38541, Republic of Korea

    Young-Mi Ah

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  1. Jillie Choi
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Contributions

All authors contributed to the study conception and design. YMY and YA conceptualized and designed the study and prepared the manuscript. JC and JEN conducted a literature search and data extraction and drafted the manuscript. JL and SAC performed the data analysis and reviewed the manuscript. WC interpreted the data and reviewed the manuscript. All authors reviewed, amended, and approved the submitted manuscript.

Corresponding authors

Correspondence to Young-Mi Ah or Yun Mi Yu.

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Supplementary Information

ESM 1

Search strategy (DOCX 18 kb)

ESM 2

Checklist for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (DOCX 20 kb)

ESM 3

On-label doses of direct oral anticoagulants (DOCX 18 kb)

ESM 4

Funnel plot analysis for thromboembolic events and major bleeding. CDLD, clinically driven low-dose; SLD, standard low-dose; STD, standard dose (PNG 261 kb)

High Resolution Image (TIF 1198 kb)

ESM 5

Meta-analysis of outcomes using the unit 100 patient-years (DOCX 19 kb)

ESM 6

Meta-analysis of outcomes using adjusted hazard ratios for clinically driven low-dose treatment (DOCX 17 kb)

ESM 7

Meta-analysis of outcomes in clinically driven low-dose, on-label dose, standard dose, and standard low-dose treatments according to each DOAC ingredient (DOCX 21 kb)

ESM 8

Quality assessments of the risk of bias according to the Risk of Bias in Non-randomized Studies - of Interventions (ROBINS-I) criteria (DOCX 24 kb)

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Choi, J., No, J.E., Lee, JY. et al. Efficacy and Safety of Clinically Driven Low-Dose Treatment with Direct Oral Anticoagulants in Asians with Atrial Fibrillation: a Systematic Review and Meta-analysis. Cardiovasc Drugs Ther 36, 333–345 (2022). https://doi.org/10.1007/s10557-021-07171-5

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