Association of statin use with 28-day mortality in the Medical Information Mart for Intensive Care IV database: a retrospective cohort study

Background: Statins, acknowledged for their ability to reduce cardiovascular risk, demonstrate a variety of pleiotropic effects, including anti-inflammatory, antithrombotic, endothelial stabilizing activity and prevention of acute kidney injury (AKI) post cardiac surgery. Patients in the intensive care unit (ICU) face heightened risks of cardiovascular disease, infections, and thrombotic complications, but the effect of statin therapy on ICU mortality remains controversial. The Medical Information Mart for Intensive Care IV (MIMIC-IV) database is a publicly available intensive care medicine information database that includes data on critically ill patients admitted to the ICU at Beth Israel Deaconess Medical Center from 2008 to 2019, with a large sample size. In this retrospective cohort study, the MIMIC-IV database was used to clarify the association between statin therapy and all-cause mortality in critically ill patients. An additional aim was to compare the effect of different statin types on mortality.

Methods: Patients aged 18 years or older, with first-time admissions and complete data, were categorized based on their use of statins during their ICU stay. The primary outcome was 28-day mortality, analyzed through multivariable Cox regression and expressed as adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). The relationship between statin therapy and 28-day mortality in ICU patients was estimated using propensity score matching (PSM) and multivariable analysis to adjust for covariates.

Results: Among the 50,624 enrolled patients, 30.9% were treated with statins. Compared to patients not receiving statin therapy, those on statins were older, had a higher proportion of males (62.0% vs. 53.1%), a greater percentage with health insurance (50.2% vs. 39.5%), and a higher rate of concurrent aspirin use (70.8% vs. 18.2%). In terms of comorbidities, patients in the statin group had higher proportions of congestive heart failure (CHF), AKI, myocardial infarction, and chronic obstructive pulmonary disease (COPD). Statin treatment in patients in the ICU was correlated with reduced 28-day all-cause mortality in the multivariate Cox analysis (statins: HR =0.66, 95% CI: 0.61–0.70; atorvastatin: HR =0.71, 95% CI: 0.66–0.78; rosuvastatin: HR =0.57, 95% CI: 0.45–0.72; simvastatin: HR =0.54, 95% CI: 0.48–0.62; other statins: HR =0.68, 95% CI: 0.56–0.83). PSM confirmed these findings (statins: HR =0.69, 95% CI: 0.63–0.75).

Conclusions: Statin use may correlate with a decreased risk of 28-day mortality in patients in the ICU, with simvastatin showing a more pronounced effect. The robustness of these findings remain unaffected in the subgroup analyses, sensitivity analyses, and PSM, indicating potential clinical significance. The high mortality rate among ICU patients means that any method capable of reducing mortality could have significant implications for ICU treatment.

Keywords: Intensive care units (ICUs); hydroxymethylglutaryl-coenzyme A reductase inhibitors (HMG-CoA reductase inhibitors); Medical Information Mart for Intensive Care IV (MIMIC-IV); mortality

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Key findings

• Through retrospective analysis of critically ill patients in the Medical Information Mart for Intensive Care IV database, it was found that statin use could potentially reduced the risk of death in patients in intensive care units (ICUs).

• Compared with other statins, simvastatin had the highest reduction of mortality among patients in the ICU.

• In patients with chronic obstructive pulmonary disorder, acute kidney injury, sepsis, or myocardial infarction, statin use was associated with reduced 28-day mortality, while the association of statin use and 28-day mortality did not differ according to sex.

What is known and what is new?

• Statins can lower blood cholesterol levels and prevent cardiovascular events in patients with cardiovascular disease.

• This study further confirmed the benefits of statin multipotency in treating patients in the ICU, which can potentially improve the prognosis of those with multiple diseases and perhaps reduce mortality.

What is the implication, and what should change now?

• The results highlight the potential effect of statins on mortality in patients in the ICU, mortality is high in severe cases, and methods to reduce mortality are meaningful for patients.

• For clinical pharmacists, this study may be useful for drug reformulation for patients in the ICU.

• Clinicians should be aware of the importance of statins and decide upon whether to add or cease statins according to the actual situation of patients and not arbitrarily.

Cite this article as: Kang C, Li F, Zhao H, Honore PM, Dagli-Hernandez C, Hoshi T, Jin Y. Association of statin use with 28-day mortality in the Medical Information Mart for Intensive Care IV database: a retrospective cohort study. J Thorac Dis 2025;17(1):429-440. doi: 10.21037/jtd-2024-2243