Effects of discontinuing or continuing ongoing statin therapy in severe sepsis and septic shock: a retrospective cohort study.

Armand Mekontso Dessap 1, 2, * Islem Ouanes 1, 3 Nerlep Rana 1 Beatrice Borghi 1 Christophe Bazin 4 Sandrine Katsahian 5 Anne Hulin 4 Christian Brun-Buisson 1, 2
* Auteur correspondant
1 Service d'anesthésie-réanimation SAMU94-SMUR94 [Mondor]
2 IMRB - Institut Mondor de Recherche Biomédicale
3 Intensive Care Unit
4 Laboratoire de pharmacologie et toxicologie
5 Unité de recherche clinique
Abstract : ABSTRACT: INTRODUCTION: Recent publications suggest potential benefits from statins as a preventive or adjuvant therapy in sepsis. Whether ongoing statin therapy should be continued or discontinued in patients admitted in the intensive care unit (ICU) for sepsis is open to question. METHODS: We retrospectively compared patients with severe sepsis and septic shock in whom statin therapy had been discontinued or continued. The primary endpoint was the number of organ failure-free days at day 14. Secondary end-points included hospital mortality and safety. The association of statin continuation with outcome was evaluated for crude analysis and after propensity score matching and adjustment. We also measured plasma atorvastatin concentrations in a separate set of ICU septic patients continuing the drug. RESULTS: Patients in whom statin therapy had been continued in the ICU (n = 44) had significantly more organ failure-free days (11 67891011121314 vs. 6 [0-12], mean difference of 2.34, 95%CI from 0.47 to 5.21, P = 0.03) as compared to others (n = 32). However, there were important imbalances between groups, with more hospital-acquired infections, more need for surgery before ICU admission, and a trend towards more septic shock at ICU admission in the discontinuation group. The significant association of statin continuation with organ failure free days found in the crude analysis did not persist after propensity-matching or multivariable adjustment: beta coefficients [95% CI] of 2.37 [-0.96 to 5.70] (P = 0.20) and 2.24 [-0.43 to 4.91] (P = 0.11) respectively. We found particularly high pre-dose and post-dose atorvastatin concentrations in ICU septic patients continuing the drug. CONCLUSIONS: Continuing statin therapy in ICU septic patients was not associated with reduction in the severity of organ failure after matching and adjustment. In addition, the very high plasma concentrations achieved during continuation of statin treatment advocates some caution.
keyword : statin discontinuation blood concentration sepsis
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Critical Care, BioMed Central, 2011, 15 (4), pp.R171. 〈10.1186/cc10317〉
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Armand Mekontso Dessap, Islem Ouanes, Nerlep Rana, Beatrice Borghi, Christophe Bazin, et al.. Effects of discontinuing or continuing ongoing statin therapy in severe sepsis and septic shock: a retrospective cohort study.. Critical Care, BioMed Central, 2011, 15 (4), pp.R171. 〈10.1186/cc10317〉. 〈inserm-00624799〉

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