Rosuvastatin (Crestor) is not effective for reducing delirium and subsequent cognitive impairment in critically ill patients with sepsis-related acute respiratory distress who require mechanical ventilation, according to ancillary findings from a randomized controlled trial.

Participants in the multicenter, nationwide Patients in the Statins for Acutely Injured Lungs from Sepsis (SAILS) trial who were treated with rosuvastatin were no less likely to experience delirium while hospitalized in intensive care than patients in the placebo arm of the study, and the two groups had similar rates of cognitive impairment at 6- and 12-months follow-up.

The findings do not support those of previous preclinical and observational studies showing statins to be associated with reduced daily delirium in intensive care, researcher Dale Needham, MD, of Johns Hopkins University, and colleagues wrote in Lancet Respiratory Medicine, published online Jan. 28.
Delirium is very common in critically ill, mechanically ventilated patients, occurring in as many as 80%, in one study. Delirium is also strongly associated with cognitive impairment lasting for a year or more after discharge.
In an email exchange, Needham told MedPage Today that more than 70% of the patients in the SAILS study who required invasive mechanical ventilation due to sepsis-associated acute respiratory distress syndrome (ARDS) experienced delirium during their ICU stay.
“Approximately one-third of surviving study participants had cognitive impairment at 12-month follow-up, which prior studies have demonstrated is associated with duration of delirium in ICU,” Needham noted. “Despite encouraging preliminary studies, this trial showed no benefit of rosuvastatin in reducing delirium in intensive care or in reducing cognitive impairment during 12 months of follow-up.”
The double-blind study was conducted at 35 hospitals located throughout the U.S., and patients were randomly assigned in blocks of eight, stratified by hospital to receive either rosuvastatin (40 mg loading dose, followed by 20 mg daily until 3 days after discharged from ICU, study day 28, or death) or placebo.

The primary endpoint was daily delirium status in ICU up to 28 days in the intention-to-treat population and secondary endpoints were cognitive function at 6- and 12-months.
A total of 272 patients were assessed for delirium daily in intensive care, and the mean proportion of days with delirium was 34% (SD 30%) in the rosuvastatin group versus 31% (SD 29%) in the placebo group (hazard ratio 1.14, 95% CI 0.92-1.41; P=0.22).
Nineteen (36%) of 53 patients in the rosuvastatin group had cognitive impairment at 6 months versus 29 (38%) of 77 in the placebo group, with no significant difference seen between groups (treatment effect, 0.93, 95% CI 0.39–2.22; P=0.87).
At 12 months, 20 (30%) of 67 patients versus 23 (28%) of 81 patients had cognitive impairment, with no significant difference between groups (treatment effect 1.1, 95% CI 0.5–2.6; P=0.82).
“To our knowledge, this is the first ancillary study of a multicenter, randomized, double-blind, placebo-controlled trial evaluating the effect of rosuvastatin compared with placebo to evaluate effects on delirium in intensive care and subsequent cognitive function in patients with sepsis-associated acute respiratory distress syndrome,” the researchers wrote.
Researchers noted that incomplete data on delirium in the SAILS study was a potential limitation of the analysis, along with possible measurement error. They also noted that rosuvastatin has less antibacterial effects and tissue penetration than other widely used statins, including atorvastatin and simvastatin.
“Hence, we cannot conclude that a different statin would not be beneficial,” they wrote. “Some experts have suggested that randomized trials of delirium should assess statins with both high and low lipophilic properties given the uncertainty about the effects on neuroinflammation. However, both a lipophilic (ie. simvastatin) and nonlipophilic (ie. rosuvastatin) statin have been assessed in large randomized trials of patients with ARDS with similar findings of no beneficial effects on mortality and ventilator-free days.”
Based on findings from their observational study suggesting a benefit for keeping critically ill patients on pre-existing statin therapy, researchers in the U.K. are conducting a clinical trial aimed at determining if statins reduce the risk of delirium in this population.
Needham told MedPage Today that the lack of efficacy in the newly published post-hoc analysis highlights the importance of conducting studies on other potential strategies to reduce delirium in critically ill patients requiring mechanical ventilation.
“There is a need to continue evaluating interventions aimed at reducing delirium in the ICU and post-ICU cognitive impairments commonly observed in this population,” he noted.