Key result
ICU statin use linked to ~18% lower 28-day sepsis mortality, but attenuates with severity adjustment.
Why the study?
Observational associations between statin exposure and mortality in sepsis may be distorted by immortal time bias and covariate timing, prompting reassessment using time-updated exposure and landmark analyses.
Does ICU statin exposure reduce 28-day all-cause mortality in adults with sepsis?
Cohort (n=10,156)
No
Does ICU statin exposure reduce 28-day all-cause mortality in adults with sepsis?
Although ICU statin exposure initially appeared associated with reduced 28-day mortality in sepsis, the association became non-significant after adjusting for first-day severity and treatments, suggesting prior observational benefits may reflect residual confounding rather than a true causal effect.
Answers are grounded in this paper and cite their sources.
Should not yet change sepsis statin prescribing; challenges prior observational data and leaves open causal effects.
Purpose Observational associations between statin exposure and mortality in sepsis may be distorted by immortal time bias and covariate timing. We reassessed this association using time-updated exposure and complementary landmark analyses in MIMIC-IV. Methods Adults with sepsis in MIMIC-IV version 3.1 were followed from ICU admission for 28-day all-cause mortality. Statin exposure changed from unexposed to exposed at the first ICU statin prescription in a counting-process Cox model adjusted for admission-known covariates. Twenty-four-hour and 48-hour landmark analyses were performed. A sensitivity analysis across five multiply imputed datasets additionally included first-day severity, laboratory variables, and treatments re-extracted within 0–24 h. Results Among 10,156 eligible patients, 2,535 received a statin during ICU stay. Time-updated statin exposure was associated with lower 28-day mortality after adjustment for admission-known covariates (HR 0.82 (95% CI 0.74-0.90; P < 0.001)). The 24-hour and 48-hour landmark estimates were similar (HR 0.84 (95% CI 0.76-0.93; P < 0.001) and HR 0.84 (95% CI 0.76−0.93; P < 0.001), respectively). The association attenuated after adjustment for first-day severity, laboratory variables, and corrected 0−24-hour treatments (multiply imputed HR 0.95 (95% CI 0.87−1.05; P = 0.310)). Conclusions Time-updated ICU statin exposure was associated with lower 28-day mortality in models using admission-known covariates and in the 24-hour and 48-hour landmark analyses. Attenuation after adding first-day clinical status indicates sensitivity to covariate specification and possible residual confounding; a causal survival benefit cannot be established.
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Wang et al. (2026) conducted a cohort in Sepsis or septic shock (n=10,156). ICU statin exposure (atorvastatin, simvastatin, rosuvastatin, pravastatin, lovastatin, fluvastatin, or pitavastatin) vs. No statin exposure during ICU stay was evaluated on 28-day all-cause mortality from ICU admission (time-varying Cox model adjusted for admission-known covariates) (HR 0.82, 95% CI 0.74-0.90, p=<0.001). Time-updated ICU statin exposure was associated with lower 28-day mortality in sepsis after adjusting for admission covariates (HR 0.82, P < 0.001), but attenuated with first-day severity adjustment.
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