The Clinical Outcome and the Cost-Effectiveness Analysis of Simvastatin plus Standard Therapy versus Standard Therapy Alone in Critically Ill Septic Patient

Abstract

The use or misuse of statins in critically ill patients recently attracted the attention of intensive care clinicians for several different reasons. First, statins are probably the most common chronic treatment before critical illness. These lipid-lowering drugs are widely prescribed (18 million prescription purchase in France and 173.7 million in the United States) (De Santé, 2010; Stagnitti, 2008), because they improve survival in patients with cardiovascular disease (Shepherd et al., 1995), and in apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels (Ridker et al., 2008). Second, the adverse effects of statins, including liver test abnormalities and rises in the plasma levels of creatine kinase, explain the withholding of statin treatment during the stay in intensive care units. Third, some experimental and clinical data demonstrated beneficial effects of statins during sepsis, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), or after subarachnoidal hemorrhage (SAH) in relation with the so-called pleiotropic effects of this class of drugs (Takemoto and Liao, 2001). These effects could benefit to these patients in relation with the associated antiinflammatory, immunomodulatory, antithrombotic, and antioxidant properties found independently of the lipid-lowering properties. Because statins do not target individual inflammatory mediators, they could modulate the overall magnitude of the inflammatory response. Even patients under statin treatment developing multiple organ dysfunction syndrome (MODS) seems to have a better outcome than age- and sex-matched MODS patients without statin therapy (Schmidt et al., 2006). These impressive findings underline the need for review clinically relevant effects of statins in the particular setting of critical