ACEI/ARB Medication During ICU Stay Decrease All-Cause In-hospital Mortality in Critically Ill Patients With Hypertension: A Retrospective Cohort Study Based on Machine Learning

Background: Hypertension is a rather common comorbidity among critically ill patients and hospital mortality might be higher among critically ill patients with hypertension (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg). This study aimed to explore the association between ACEI/ARB medication during ICU stay and all-cause in-hospital mortality in these patients. Methods: A retrospective cohort study was conducted based on data from Medical Information Mart for Intensive Care IV (MIMIC-IV) database, which consisted of more than 40,000 patients in ICU between 2008 and 2019 at Beth Israel Deaconess Medical Center. Adults diagnosed with hypertension on admission and those had high blood pressure (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg) during ICU stay were included. The primary outcome was all-cause in-hospital mortality. Patients were divided into ACEI/ARB treated and non-treated group during ICU stay. Propensity score matching (PSM) was used to adjust potential confounders. Nine machine learning models were developed and validated based on 37 clinical and laboratory features of all patients. The model with the best performance was selected based on area under the receiver operating characteristic curve (AUC) followed by 5-fold cross-validation. After hyperparameter optimization using Grid and random hyperparameter search, a final LightGBM model was developed, and Shapley Additive exPlanations (SHAP) values were calculated to evaluate feature importance of each feature. The features closely associated with hospital mortality were presented as significant features. Results: A total of 15,352 patients were enrolled in this study, among whom 5,193 (33.8%) patients were treated with ACEI/ARB. A significantly lower all-cause in-hospital mortality was observed among patients treated with ACEI/ARB (3.9 vs. 12.7%) as well as a lower 28-day mortality (3.6 vs. 12.2%). The outcome remained consistent after propensity score matching. Among nine machine learning models, the LightGBM model had the highest AUC = 0.9935. The SHAP plot was employed to make the model interpretable based on LightGBM model after hyperparameter optimization, showing that ACEI/ARB use was among the top five significant features, which were associated with hospital mortality. Conclusions: The use of ACEI/ARB in critically ill patients with hypertension during ICU stay is related to lower all-cause in-hospital mortality, which was independently associated with increased survival in a large and heterogeneous cohort of critically ill hypertensive patients with or without kidney dysfunction.