Search for therapeutic agents for cardiac arrest using a drug discovery tool and large-scale medical information database

Yoshito Zamami, Takahiro Niimura, Toshihiro Koyama, Yuta Shigemi, Yuki Izawa-Ishizawa, Mizuki Morita, Ayako Ohshima, Keisaku Harada, Toru Imai, Hiromi Hagiwara, Naoto Okada, Mitsuhiro Goda, Kenshi Takechi, Masayuki Chuma, Yutaka Kondo, Koichiro Tsuchiya, Shiro Hinotsu, Mitsunobu R. Kano, Keisuke Ishizawa

Research output: Contribution to journalArticle

Abstract

The survival rate of cardiac arrest patients is less than 10%; therefore, development of a therapeutic strategy that improves their prognosis is necessary. Herein, we searched data collected from medical facilities throughout Japan for drugs that improve the survival rate of cardiac arrest patients. Candidate drugs, which could improve the prognosis of cardiac arrest patients, were extracted using “TargetMine,” a drug discovery tool. We investigated whether the candidate drugs were among the drugs administered within 1 month after cardiac arrest in data of cardiac arrest cases obtained from the Japan Medical Data Center. Logistic regression analysis was performed, with the explanatory variables being the presence or absence of the administration of those candidate drugs that were administered to ≥10 patients and the objective variable being the “survival discharge.” Adjusted odds ratios for survival discharge were calculated using propensity scores for drugs that significantly improved the proportion of survival discharge; the influence of covariates, such as patient background, medical history, and treatment factors, was excluded by the inverse probability-of-treatment weighted method. Using the search strategy, we extracted 165 drugs with vasodilator activity as candidate drugs. Drugs not approved in Japan, oral medicines, and external medicines were excluded. Then, we investigated whether the candidate drugs were administered to the 2,227 cardiac arrest patients included in this study. The results of the logistic regression analysis showed that three (isosorbide dinitrate, nitroglycerin, and nicardipine) of seven drugs that were administered to ≥10 patients showed significant association with improvement in the proportion of survival discharge. Further analyses using propensity scores revealed that the adjusted odds ratios for survival discharge for patients administered isosorbide dinitrate, nitroglycerin, and nicardipine were 3.35, 5.44, and 4.58, respectively. Thus, it can be suggested that isosorbide dinitrate, nitroglycerin, and nicardipine could be novel therapeutic agents for improving the prognosis of cardiac arrest patients.

Original languageEnglish
Article number1257
JournalFrontiers in Pharmacology
Volume10
DOIs
Publication statusPublished - 2019

Keywords

  • Cardiac arrest
  • Claims database
  • Drug discovery tool
  • Drug repositioning
  • Vasodilator

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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    Zamami, Y., Niimura, T., Koyama, T., Shigemi, Y., Izawa-Ishizawa, Y., Morita, M., Ohshima, A., Harada, K., Imai, T., Hagiwara, H., Okada, N., Goda, M., Takechi, K., Chuma, M., Kondo, Y., Tsuchiya, K., Hinotsu, S., Kano, M. R., & Ishizawa, K. (2019). Search for therapeutic agents for cardiac arrest using a drug discovery tool and large-scale medical information database. Frontiers in Pharmacology, 10, [1257]. https://doi.org/10.3389/fphar.2019.01257