A logistic regression model based on inpatient health records to predict drug-induced liver injury caused by ramipril-An angiotensin-converting enzyme inhibitor

PLoS One. 2022 Aug 17;17(8):e0272786. doi: 10.1371/journal.pone.0272786. eCollection 2022.

Abstract

Drug-induced liver injury (DILI) is a rare side effect of angiotensin-converting enzyme inhibitors (ACEIs). Ramipril is a widely used ACE compound because of its effectiveness in the treatment of hypertension and heart failure, as well as its low risk of adverse effects. However, the clinical features of ramipril, and the risk of DILI, have not been adequately studied. A retrospective cohort study was performed based on data from 3909 inpatients to compare the risk of DILI conferred by ramipril and other ACEIs. A logistic regression model was then constructed and validated against data from 1686 patients using ramipril, of which 117 patients were diagnosed with DILI. The use of ramipril increased the risk of DILI by 2.68 times (odds ratio = 2.68; 95% confident interval (CI):1.96-3.71) compared with the group using other ACEIs. The clinical features of DILI in the ramipril group were similar to those from the ACEI group (P>0.05), except that the ALT level was higher (P<0.05). A logistic regression model including Body mass index (BMI), comorbidity, liver disease, daily dose, alanine aminotransferase (ALT), and alkaline phosphatase (ALP) was built and successfully validated for DILI risk prediction, with the area under the receiver operating characteristic curve of the model of 0.82 (95% CI: 0.752-0.888). We recommend that clinicians should be aware of the levels of ALT and ALP as well as BMI, comorbidities, and liver disease before prescribing ramipril to avoid the risk of DILI in patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Chemical and Drug Induced Liver Injury* / drug therapy
  • Chemical and Drug Induced Liver Injury* / epidemiology
  • Chemical and Drug Induced Liver Injury* / etiology
  • Humans
  • Inpatients
  • Logistic Models
  • Ramipril* / adverse effects
  • Retrospective Studies

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Ramipril

Grants and funding

This work is funded by Haiphong University of Medicine and Pharmacy.