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Association between anemia and mortality in patients with acute coronary syndrome treated with percutaneous coronary intervention and contemporary lipid-lowering therapy

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Abstract

Despite a clear correlation between anemia and mortality in patients with the acute coronary syndrome (ACS), anemia as a mortality predictor in patients with ACS-receiving early invasive strategy and contemporary lipid-lowering therapy has not been examined. Therefore, we aimed to evaluate the association between anemia and mortality in ACS patients treated with acute revascularization and contemporary lipid-lowering treatment. This was a post-hoc study of the Heart Institute of Japan-Proper level of Lipid-Lowering with Pitavastatin and Ezetimibe in acute coronary syndrome study, in which ACS patients with dyslipidemia were randomized to receive either pitavastatin and ezetimibe or pitavastatin monotherapy. The success rate of primary percutaneous coronary intervention (PCI) was 95.2%. Eligible patients were divided into two groups: patients with anemia (anemia group) or without anemia (non-anemia group). Anemia was defined using the World Health Organization definition hemoglobin < 12 g/dL for women and < 13 g/dL for men. We compared the mortality between the two groups using propensity scores derived from 17 baseline variables. We identified 1721 eligible patients, including 420 (24.4%) in the anemia group and 1301 (75.6%) in the non-anemia group. One-to-one propensity score-matching created 381 pairs. Both unmatched and matched analyses found significantly high mortality in the anemia group compared to the non-anemia group (unmatched 12.3% vs. 3.8%, log-rank p < 0.01; matched 11.5% vs. 6.3%, log-rank p = 0.01). In ACS patients treated with an early invasive strategy era with a high PCI success rate and concurrent contemporary lipid-lowering management, all-cause mortality was still significantly higher in anemic patients than in non-anemic patients.

Trial registration: Clinical trial registration URL: http://www.umin.ac.jp/ctr. Unique identifier: UMIN00000274

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Acknowledgements

We thank the HIJ-PROPER participants as well as the staff and investigators of the HIJ-PROPER study for their contributions, and the participating centers, Ebara Metropolitan Hospital (Tokyo), Tokyo Metropolitan Tama Medical Center Hospital (Tokyo), Tokyo Metropolitan Tama-Hokubu Medical Center Hospital (Tokyo), Kosei General Hospital (Tokyo), Nishiarai Hospital (Tokyo), Kanto Medical Center NTT East (Tokyo), Saiseikai Kurihashi Hospital (Saitama), Saiseikai Kumamoto Hospital (Kumamoto), Seirei Hamamatsu Hospital (Shizuoka), Sendai Cardiovascular Center (Miyagi), Shin-Matsudo-Chuo General Hospital (Chiba), Shiseikai Second Hospital (Tokyo), The Sakakibara Heart Institute (Tokyo), Yokohama Medical Center (Kanagawa), Tokyo Women’s Medical University Medical Center East (Tokyo), and Tokyo Women’s Medical University (Tokyo). We thank Dr. Toshiaki Isogai for statistical advice. We would also like to thank Editage (https://www.editage.com) for English language editing and Publication Support.

Funding

The original trial was funded by the Japan Research Promotion Society for Cardiovascular Diseases. No additional extramural funding was used to support this work.

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Authors and Affiliations

  1. Department of Cardiology, The Heart Institute of Japan, Tokyo Women’s Medical University, 8-1, Kawada-Cho, Shinjuku, Tokyo, 162-8666, Japan

    Masataka Ogiso, Junichi Yamaguchi, Hisao Otsuki, Hiroyuki Arashi, Haruki Sekiguchi, Hiroshi Ogawa & Nobuhisa Hagiwara

Authors
  1. Masataka Ogiso
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  2. Junichi Yamaguchi
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  3. Hisao Otsuki
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  5. Haruki Sekiguchi
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  6. Hiroshi Ogawa
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  7. Nobuhisa Hagiwara
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Contributions

Dr. HA, Dr. JY, Dr. HO, and Dr. NH conceptualized and designed the original study. Dr. MO and Dr. JY analyzed and interpreted the data. Dr. MO and Dr. JY drafted and wrote the manuscript. Dr. HO and Dr. NH reviewed the manuscript. All authors, both external and internal, had full access to all the data, including the statistical reports and tables, from the study and are responsible for the integrity of the data and the analyses’ accuracy.

Corresponding author

Correspondence to Junichi Yamaguchi.

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Conflict of interest

All members of the HIJ-PROPER study group report receiving research support to perform clinical trials through the Japan Research Promotion Society for Cardiovascular Diseases, which is sponsored by Abbott Vascular Japan Co., Ltd., AstraZeneca K.K., Bayer Yakuhin, Ltd., Boston Scientific Corporation, Bristol-Myers K.K., Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., and Takeda Pharmaceutical Company Limited. N. Hagiwara reports that he has received honoraria from Bristol-Myers K.K. and Nippon Boehringer Ingelheim Co., Ltd., and grants from Astellas Pharma Inc., Daiichi Sankyo Company, Limited, Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., and Takeda Pharmaceutical Company Limited. J. Yamaguchi and H. Otsuki belong to the division (Clinical Research division for Cardiovascular Catheter Intervention) financially maintained by the donation from Abbott Vascular, Boston Scientific, Medtronic Terumo. All authors have reported that they have no relationships relevant to the contents of this paper to disclose. The HIJ-PROPER Steering Committee had full access to all data in the study and had final responsibility for the decision to submit for publication.

Ethical approval

All procedures performed in studies involving human participants followed the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The present study was approved by the institutional review board of the Tokyo Women’s Medical University (Reference number: 1741).

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Informed consent was obtained from all individual participants included in the study.

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Ogiso, M., Yamaguchi, J., Otsuki, H. et al. Association between anemia and mortality in patients with acute coronary syndrome treated with percutaneous coronary intervention and contemporary lipid-lowering therapy. Heart Vessels 36, 1626–1634 (2021). https://doi.org/10.1007/s00380-021-01850-x

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