Association between pravastatin use and short-term mortality in ICU patients with sepsis: a retrospective propensity...

Sepsis is a life-threatening condition with persistently high mortality in the ICU, highlighting an urgent need for effective pharmacological interventions. Statins have been proposed as potential adjunctive therapies owing to their pleiotropic properties, but evidence specifically supporting the use of pravastatin-a hydrophilic statin with distinct pharmacokinetics-in this critically ill population remains insufficient.

This retrospective cohort study utilized data from the MIMIC-IV database (version 3.1). Adult patients with sepsis at their first ICU admission who received pravastatin within the first 24 hours of ICU admission were included, while those using other statins were excluded. Propensity score matching (PSM) was performed at a 1:1 ratio to balance baseline characteristics between the pravastatin and non-pravastatin groups. The primary outcome was 28-day all-cause mortality. Secondary outcomes included in-hospital mortality, in-ICU mortality, and the incidence of acute kidney injury (AKI) and continuous renal replacement therapy (CRRT). Cox regression models were employed, and pre-specified subgroup analyses were conducted. Sensitivity analyses, including an expanded Cox model, overlap-weighted regression, and E-value analysis, were performed to assess the robustness of the findings.

From 546,028 admissions, 25,573 septic patients were identified. After PSM, 1,106 patients (553 per group) were included. The 28-day mortality rate was 11.6% (64/553) in the pravastatin group vs. 17.2% (95/553) in the non-pravastatin group. In the overall matched cohort, pravastatin use was associated with significantly lower 28-day mortality in both unadjusted (HR, 0.66; 95% CI, 0.48-0.90; P = 0.009) and fully adjusted models (HR, 0.69; 95% CI, 0.50-0.95; P = 0.025). Pravastatin was associated with reduced in-hospital mortality, while in-ICU mortality did not reach statistical significance after full adjustment. No significant differences were observed in AKI (79.6% vs. 81.7%; adjusted OR, 0.79; 95% CI, 0.57-1.10; P = 0.170) or CRRT use (4.0% vs. 5.8%; adjusted OR, 0.65; 95% CI, 0.32-1.30; P = 0.221). Subgroup analyses showed consistent associations across most strata, with no significant interactions (all P > 0.05). Timing analysis showed that in patients with pre-existing pravastatin use who continued treatment after ICU admission, continuation of pre-existing pravastatin was associated with reduced 28-day mortality (adjusted HR, 0.35; 95% CI, 0.17-0.73; P = 0.005). In patients with de novo initiation of pravastatin within 24 hours of ICU admission, no statistically significant association with 28-day mortality was observed after full adjustment (adjusted HR, 0.80; 95% CI, 0.57-1.13; P = 0.198). Sensitivity analyses yielded consistent results (expanded Cox: HR, 0.66; OW: HR, 0.70; E-value: 2.26 with lower bound 1.29).

In this retrospective analysis of septic ICU patients, continuation of pre-existing pravastatin use after ICU admission was associated with lower 28-day and in-hospital mortality, without an increased risk of AKI or CRRT use. De novo pravastatin initiation within 24 hours of ICU admission was not associated with reduced 28-day mortality. These hypothesis-generating findings warrant confirmation in future prospective studies.