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Efficacy and safety of low intensity vitamin K antagonists in Western and East-Asian patients with left-sided mechanical heart valves

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Abstract

The optimal INR target in patients with mechanical heart valves is unclear. Higher INR targets are often used in Western compared with East Asian countries. The objective of this systematic review and meta-analysis was to summarize the evidence for the efficacy and safety of lower versus higher INR targets in Western and East Asian left-sided mechanical heart valve patients. We searched Western databases including Cochrane CENTRAL, Medline, and Embase as well as Chinese databases including SinoMed, CNKI, and Wanfang Data in addition to grey literature for Randomized Controlled Trials (RCTs) and observational studies. We pooled risk ratios (RRs) using random-effects model. Low and high INR targets were defined by the individual studies. We identified nine RCTs, including six Western (n = 5496) and three East Asian (n = 209) trials, and 17 observational studies, including two Western (n = 3199) and 15 East Asian (n = 5485) studies. In the RCTs, lower compared with higher targets were associated with similar rates of thromboembolism (2.4 vs. 2.3%; RR: 1.14, 95% CI 0.82, 1.60, I2 = 0%) and lower rates of both total bleeding (21.9 vs. 40.9%, RR: 0.46, 95% CI 0.28, 0.78, I2 = 88%) and major bleeding. RCT data showed no statistical heterogeneity by region. These effects were consistent in the observational data. We downgraded the quality of evidence due to serious risk of bias and imprecision. In patients with left-sided contemporary mechanical heart valves, low quality evidence suggests lower INR targets are associated with similar rates of thromboembolism and moderate quality evidence suggests lower rates of bleeding.

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Acknowledgements

Mr. Pandey has nothing to disclose. Dr. Xu has nothing to disclose. Dr. Zhang has nothing to disclose. Dr. Gupta has nothing to disclose. Dr. Crowther reports grants and other from Bayer, personal fees from Pfizer, personal fees from CSL Behring, personal fees from Servier Canada, personal fees from Diagnostica Stago, personal fees from Asahi Kasei, outside the submitted work. Dr. Belley-Cote reports grants from Bayer, grants from Roche, outside the submitted work; Dr. Whitlock reports grants from Bayer, grants from Roche, grants from Boeringer-Ingelheim, other from Boeringer-Ingelheim, other from AtriCure, other from PhaseBio, outside the submitted work. Dr. Eikelboom reports honoraria and grant support from Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol-Myers-Squibb/Pfizer, Daiichi Sankyo, Glaxo Smith Kline, Janssen, sanofi aventis and Eli Lilly as well as a personnel award from the Heart and Stroke Foundation. Dr. Lopes reports personal fees from Bayer, personal fees from Boehringer Ingleheim, grants and personal fees from Bristol-Myers Squibb, personal fees from Daiichi Sankyo, grants and personal fees from Glaxo Smith Kline, grants and personal fees from Medtronic, personal fees from Merck, grants and personal fees from Pfizer, personal fees from Portola, grants and personal fees from Sanofi, outside the submitted work.

Funding

This systematic review and meta-analysis received no funding or financial support from any parties whatsoever.

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Authors and Affiliations

  1. Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Canada

    Arjun K. Pandey

  2. Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China

    Ke Xu

  3. Banner University Medical Center, Tucson, USA

    Li Zhang

  4. Division of Cardiac Surgery, Department of Surgery, McMaster University, Hamilton, Canada

    Saurabh Gupta & Richard P. Whitlock

  5. Department of Medicine, McMaster University, Hamilton, Canada

    John Eikelboom & Mark Crowther

  6. Population Health Research Institute, 237 Barton Street East, Hamilton, ON, Canada

    John Eikelboom, Emilie P. Belley-Côté & Richard P. Whitlock

  7. Duke Clinical Research Institute, Durham, USA

    Renato D. Lopes

  8. Duke University School of Medicine, Durham, USA

    Renato D. Lopes

  9. Division of Hematology, Department of Medicine, McMaster University, Hamilton, Canada

    Mark Crowther

  10. Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada

    Emilie P. Belley-Côté & Richard P. Whitlock

  11. Division of Cardiology, Department of Medicine, McMaster University, Hamilton, Canada

    Emilie P. Belley-Côté

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Pandey, A.K., Xu, K., Zhang, L. et al. Efficacy and safety of low intensity vitamin K antagonists in Western and East-Asian patients with left-sided mechanical heart valves. J Thromb Thrombolysis 53, 697–707 (2022). https://doi.org/10.1007/s11239-021-02568-3

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