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Effect of lanthanum carbonate and calcium carbonate on the progression of coronary artery calcification among hemodialysis patients with vascular calcification risk: a randomized controlled trial

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Abstract

Background

Coronary artery calcification (CAC) is predictive of cardiovascular events. We assessed whether a non-calcium-based phosphate binder, lanthanum carbonate (LC), could delay CAC progression compared with a calcium-based phosphate binder, calcium carbonate (CC), in hemodialysis patients.

Methods

This was a subsidiary of the LANDMARK study, which is a multicenter, open-label, randomized control study comparing LC and CC for cardiovascular events among Japanese hemodialysis patients with hyperphosphatemia who were at risk of vascular calcification. Participants were randomly assigned (1:1) to receive LC or CC. The changes in the total Agatston score of CAC 2 years from baseline were the primary outcome. Secondary outcomes included the changes in the total Agatston score at 1 year from baseline and the changes in serum phosphate, corrected calcium, and intact parathyroid hormone concentrations.

Results

Of 239 patients, 123 comprised the full analysis set. The median daily drug dose (mg) was 750 [interquartile range (IQR), 750‒1500] in the LC group and 3000 (IQR, 3000‒3000) in the CC group; it remained constant throughout the study period. There was no significant difference in the change in total Agatston score from baseline to 2 years between the LC and CC groups [368 (95% confidence interval, 57–680) in the LC group vs. 611 (105–1118) in the CC group; difference, 243 (− 352–838)].

Conclusions

LC-based treatment for hyperphosphatemia did not delay CAC for 2 years compared with CC-based treatment in hemodialysis patients with at least one risk factor for vascular calcification.

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Acknowledgements

We acknowledge the contribution of the LANDMARK Investigators and Committees.

Funding

This study was supported by Bayer Yakuhin, Ltd. Bayer Yakuhin, Ltd. had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. However, the company was kept informed of the progress of the study. There were no confidentiality agreements regarding the data.

Author information

Authors and Affiliations

  1. Division of Nephrology, Department of Internal Medicine, Showa University Northern Yokohama Hospital, Chigasaki-chuo 35-1, Tsuzuki, Yokohama, Kanagawa, 224-8503, Japan

    Hiroaki Ogata

  2. Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan

    Masafumi Fukagawa

  3. Fukuoka Renal Clinic, Chuo-ku, Fukuoka, Japan

    Hideki Hirakata

  4. The Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Chuo-ku, Kobe, Hyogo, Japan

    Tatsuo Kagimura

  5. Division of Nephrology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan

    Tadao Akizawa

Authors
  1. Hiroaki Ogata
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  2. Masafumi Fukagawa
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  3. Hideki Hirakata
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  4. Tatsuo Kagimura
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Consortia

the LANDMARK Investigators and Committees

Contributions

Research idea and study design: MF, HH, TA; data acquisition: TK; data analysis/interpretation: HO, MF, HH, TK, TA; statistical analysis: HO, TK; drafting of this manuscript: HO, TK; supervision or mentorship: MF, HH, TA. Each author contributed toward important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual’s contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate.

Corresponding author

Correspondence to Hiroaki Ogata.

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Conflict of interest

Dr Ogata reported receiving lecture fees from Bayer Yakuhin, Kyowa Kirin, Torii Pharmaceutical, Otsuka, Kissei Pharmaceutical, Mitsubishi Tanabe Pharma, Sumitomo Dainippon Pharm, Daiichi Sankyo, Kowa, Ono Pharmaceutical; grants from Torii Pharmaceutical and Ono Pharmaceutical; and consulting fees from YL Biologics. Dr Fukagawa reported receiving personal fees from Bayer Yakuhin and grants from Kyowa Kirin. Dr Hirakata reported receiving personal fees from Kyowa-Kirin, Chugai Pharma, Torii, Japan Tobacco, and Ono Yakuhin. Dr Kagimura reported receiving grants from Bayer Yakuhin. Dr Akizawa reported receiving consulting and lecture fees from Bayer Yakuhin, Astellas, Kyowa Kirin, Kissei Pharmaceutical, Ono Pharmaceutical, Fuso Pharmaceutical Industry, Torii Pharmaceutical; consulting fees from GlaxoSmithKline, JT Pharmaceutical, Nipro Corporation, Otsuka, and Sanwa Chemical; and lecture fees from Chugai Pharmaceutical. No other disclosures were reported.

Ethical approval

The trial protocol of the LANDMARK study was previously published and was approved by the Institutional Review Board. All patients enrolled in this LANDMARK-SS study provided written informed consent.

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Ogata, H., Fukagawa, M., Hirakata, H. et al. Effect of lanthanum carbonate and calcium carbonate on the progression of coronary artery calcification among hemodialysis patients with vascular calcification risk: a randomized controlled trial. Clin Exp Nephrol 26, 1223–1232 (2022). https://doi.org/10.1007/s10157-022-02270-5

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  • DOI: https://doi.org/10.1007/s10157-022-02270-5

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