Tuesday, January 24, 2006

Wednesday January 25, 2006
Statins – Adjuvant Therapy for Sepsis

Statins are powerful hypolipemic drugs with pleiotropic effects and have been shown to improve survival in the primary and secondary prevention of atherosclerosis in numerous large randomized clinical trials. Interestingly, in many of these trials, their beneficial clinical impact included noncoronary events. Several cellular and animal models demonstrate the pleiotropic activity of statins, including anti-inflammatory and anti-oxidative properties, immunomodulatory effects, improvement in endothelial function, reduction in blood thrombogenicity, and increased nitric oxide (NO) bioavailability. Some or all of these effects may account for a substantial potential impact of statins on the complex pro- and anti-inflammatory sequence of events occurring during sepsis. A few clinical studies have been published recently in support of this hypothesis.

Almog et al. conducted a prospective observational cohort study to determine the impact of statin pretreatment on the occurrence of severe sepsis in infected patients. Of 361 patients with confirmed acute bacterial infection, 82 (23%) had been receiving statins for at least 4 weeks prior to their admission. The crude mortality rate was low and did not differ significantly between the two groups (3.7% vs. 8.6%, P=0.21), but severe sepsis developed in 2.4% and 19% of patients, respectively, in the statin and no-statin group (risk ratio 0.13; 95% CI, 0.03–0.52), and the ICU admission rate was 12.2% for the no-statin group compared with only 3.7% of the statin group (P=0.025).

In another retrospective review of 388 patients with bacteremia, Liappis et al reported a significant reduction in both overall (6% vs. 28%, P=0.002) and attributable (3% vs. 20%, P=0.010) mortality among patients taking statins at the time of admission compared with patients not taking statins. The survival benefit persisted after adjustment for prognostic factors in a multivariate analysis (odds ratio 7.6; 95% CI, 1.01–57.5).

The available evidence today suggests that the potential for statins as adjuvant therapy for sepsis should be further tested. Given their pleiotropic effects related to many pathophysiologic determinants of sepsis, statin therapy could well be the next step in the search for adjuvant therapy.

References: click to get article/abstract
1. Almog Y, Shefer A, Novack V, Maimon N, Barski L, Eizinger M, Friger M, Zeller L, Danon A (2004)
Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation 110:880–885
2. Liappis AP, Kan VL, Rochester CG, Simon GL (2001)
The effect of statins on mortality in patients with bacteremia. Clin Infect Dis 33:1352–1357 -http://www.journals.uchicago.edu/CID/journal/issues/v33n8/001561/001561.html