Statins in Sepsis

There is a growing body of animal data to suggest that statins may be helpful in treating septic patients. Data in humans, for the most part, are lacking. In a prospective observational cohort study it was found that prior statin therapy is associated with a decreased rate of severe sepsis and ICU admission in patients admitted with acute bacterial infections as well as a trend towards reduced mortality [Circulation 110: 880, 2004]. In another large, community-based prospective study in which 11,362 patients were followed for up to 3 years (Almog and coworkers, unpublished data), therapy with statins may have been associated with a reduced rate of infection-related mortality. A population-based cohort analysis of 141,487 patients > 65 years with atherosclerotic disease, propensity-based matching of 69,168 patients, 50% on statins and 50% not found that the incidence of sepsis was lower in patients receiving statins than in controls (hazard ratio 0.81; 95% CI 0.72-0.90). The protective association between statins and sepsis persisted in high-risk subgroups, including patients with diabetes mellitus, chronic renal failure, or a history of infections. Significant reductions in severe sepsis (HR 0.83; 95% CI 0.70-0.97) and fatal sepsis (0.75; 0.61-0.93) were also observed [Lancet 367: 413, 2006]. A retrospective cohort analysis of 438 patients requiring hospital care for bacteremia showed a significant reduction in all-cause hospital mortality (10.6% vs. 23.1%, p=0.022) and death attributable to bacteremia (6.1% vs. 18.3%, p=0.014) in patients who were receiving statin therapy at the time of bacteremia (n=66). The reduction in all-cause hospital mortality (1.8% vs. 23.1%, p=0.0002) and death attributable to bacteremia (1.8% vs. 18.3%, p=0.0018) was more pronounced in the patients who continued to receive statin therapy after the diagnosis of bacteremia (n=56). Statin use prior to admission was associated with a reduced adjusted hospital mortality rate (odds ratio 0.39; CI 95% 0.17, 0.91; p=0.029), and continuing statin use after bacteremia increased this effect (odds ratio 0.06; CI 95% 0.01, 0.44; p=0.0056) [Schiller et al]

The promise of these earlier studies was refuted by a recent RCT of approximately 150 patients suspected of infection and who were on pre-existing statin therapy, half of whom were continued and half of whom were not [Kruger et al.].