Effect of statin therapy on mortality from infection and sepsis: a meta-analysis of randomized and observational studies

Abstract

IntroductionObservational data have suggested that statin therapy may reduce mortality in patients with infection and sepsis; however, results from randomized studies are contradictory and do not support the use of statins in this context. Here, we performed a meta-analysis to investigate the effects of statin therapy on mortality from infection and sepsis.MethodsWe searched electronic databases (PubMed and Embase) for articles published before November 2013. Randomized or observational studies reporting the effects of statin therapy on mortality in patients with infection or sepsis were eligible. Randomized and observational studies were separately pooled with relative risks (RRs) and random-effects models.ResultsWe examined 5 randomized controlled trials with 867 patients and 27 observational studies with 337,648 patients. Among the randomized controlled trials, statins did not significantly decrease in-hospital mortality (RR, 0.98; 95% confidence interval (CI), 0.73 to 1.33) or 28-day mortality (RR, 0.93; 95% CI, 0.46 to 1.89). However, observational studies indicated that statins were associated with a significant decrease in mortality with adjusted data (RR, 0.65; 95% CI, 0.57 to 0.75) or unadjusted data (RR, 0.74; 95% CI, 0.59 to 0.94).ConclusionsLimited evidence suggests that statins may not be associated with a significant reduction in mortality from infection and sepsis. Although meta-analysis from observational studies showed that the use of statins was associated with a survival advantage, these outcomes were limited by high heterogeneity and possible bias in the data. Therefore, we should be cautious about the use of statins in infection and sepsis.

Is There Potential for Repurposing Statins as Novel Antimicrobials?

“…The majority of clinical studies to date have been retrospective cohort studies evaluating the impact of prior treatment with statins on disease progression and mortality. Many of these, plus several meta-analysis reviews, showed promising results in which prior use of statins significantly reduced disease progression and/or mortality associated with sepsis (25,(28)(29)(30)(31)(32) Therefore, several studies have shown the promising potential of the prior use of statins in reducing the initiation or progression of infections. Nevertheless, it is difficult to draw conclusions on whether the effects of these statins were directly antibacterial/antiinflammatory or were due to pleitropic effects on comorbidities associated with the infections.…”

“…A recent randomized control trial (RCT) investigating the effect of rosuvastatin on the clinical outcome of patients with sepsis-associated acute respiratory distress syndrome was discontinued because of futility (35). Moreover, a number of recent meta-analyses of RCTs suggested that there is no significant evidence to suggest that statin use improves the mortality outcome of patients with sepsis (25)(26)(27).…”

“…Sepsis is a serious infection-induced whole-body inflammatory state, and, due to the immunomodulatory activity of statins, several studies have been carried out to evaluate the benefit of statin therapy in the prevention or treatment of the disease. While the type, design, size, and measured outcomes of the studies have been varied and overall results conflicting, in recent years extensive reviews evaluating these clinical studies have been published (21)(22)(23)(24)(25)(26)(27). The majority of clinical studies to date have been retrospective cohort studies evaluating the impact of prior treatment with statins on disease progression and mortality.…”

Statins in patients with sepsis and ARDS: is it over? Yes

“…Initial observational studies showed promising results, and a meta-analysis of adjusted estimates from 26 observational studies (336,245 patients) showed a significant reduction in mortality with statin use [relative risk (RR) 0.65; 95 % CI 0.57, 0.75] [5]. However, randomized clinical trials (RCTs) failed to show mortality benefit with statins use.…”

Statins in patients with sepsis and ARDS: is it over? No

“…A recent meta-analysis [7] of observational studies which pooled the data from over 330,000 patients concluded that statin use in sepsis is associated with improved outcomes. This conclusion clearly comes with many caveats, mainly that association does not confirm causation and the multiple occasions introducing bias.…”