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Recent research showed that ICU statin therapy was associated with significantly lower 28-day all-cause mortality for critically ill patients with sepsis.

Statin use is associated with significantly lower 28-day all-cause mortality for critically ill patients with sepsis, according to a study published online in Frontiers in Immunology.

“Given the wide use of statins for the prevention of cardiovascular disease, it is likely that their use in this population has also conferred benefits in combating infections and sepsis,” wrote study author Keliang Xie, MD, PhD, of Tianjin Medical University General Hospital, and study coauthors.

“Alarmingly High” Mortality Spurs Study

Citing “alarmingly high” mortality in patients with sepsis despite early goal-directed therapy, the researchers investigated whether the pleiotropic effect of statins, which includes anti-inflammatory and antimicrobial properties, impacted outcomes for patients in the ICU.

Using the Medical Information Mart for Intensive Care-IV database, the authors reviewed health record data from 20,230 adults with sepsis treated in the Beth Israel Deaconess Medical Center ICU between 2008 and 2019. Statin exposure during the ICU stay defined the treatment cohort. Propensity score matching (PSM) for a slate of variables balanced 6,070 patients who had received statin therapy during their ICU stay with an equal number of patients who had not received statin therapy during their ICU stay, creating a quasi-randomized comparison without the logistical barriers of a prospective trial.

Primary Mortality Benefit

The researchers discovered that 28-day all-cause mortality was 14.3% among the statin group versus 23.4% for control group (hazard ratio [HR], 0.56; 95% CI, 0.52-0.61; P<0.001). A sensitivity analysis in the unmatched cohort reproduced the effect (HR, 0.56). Benefit held across BMI strata, cerebrovascular disease, and heart-failure subgroups, with the underweight group showing a similar but nonsignificant trend due to small numbers.

“In subgroup analysis, this beneficial effect was consistent across the different baseline characteristics of patients,” the authors noted.

Secondary End Points Reveal Competing Risks

According to the authors, statin therapy also reduced ICU mortality (odds ratio [OR], 0.43) and in-hospital mortality (OR, 0.50) but modestly lengthened ICU stay (mean, +0.34 day), total hospitalization (+1.44 days), mechanical ventilation time (+3 hours), and continuous renal replacement therapy duration (+26 hours).

“These paradoxical findings likely reflect competing risk dynamics, wherein the mortality benefit permits extended survival of critically ill patients requiring prolonged intensive care and organ support,” the researchers suggested.

Strengths, Caveats, & Conclusion

The authors noted that although the large sample and rigorous PSM delivered doubly robust, real-world evidence, residual confounding cannot be excluded, individual statin effects were not parsed, and pre-ICU statin exposure was unmeasured.

Nonetheless, the study team concluded, “…our study suggests that statin use during the ICU stay may exert a protective effect in patients with sepsis.”