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.
Highlights
Despite advances in treatment, cardiac arrest still results in a high mortality rate
After further shortlisting for the drugs administered within 1 month from the day of cardiac arrest, 11 drugs were obtained
After exclusion of drugs that were used by ≤10 patients and those included in statistical analysis as covariates, seven drugs were shortlisted as the drug candidates for this study
Summary
Cardiac arrest still results in a high mortality rate. In the United States alone, more than 550,000 cardiac arrest cases are reported annually, with the survival discharge rate being only 12% and 24.8% for out-ofhospital and in-hospital patients, respectively (The American Heart Association, 2013). Cardiac arrest damages heart functions and those of other organs. It results in myocardial dysfunction at the early stages after resuscitation; circulation becomes very unstable (Jentzer et al, 2015). Myocardial dysfunction is associated with early death, and if improvement in cardiac function cannot be achieved within 24 h, conditions such as multiple organ failure, which have poor prognosis, are known to occur (Laurent et al, 2002). Normalization of hemodynamics is very important for improving the prognosis after cardiac arrest
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