A Population-Based Cohort Study on the Drug-Specific Effect of Statins on Sepsis Outcome

Published:September 26, 2017DOI:https://doi.org/10.1016/j.chest.2017.09.024

      Background

      Whether statin treatment, proved by recent experimental studies to have an antimicrobial activity, exerts a drug- or a class-specific effect in sepsis remains unknown.

      Methods

      Short-term mortality in patients with sepsis was analyzed using data from the National Health Insurance Research Database. Use of statins was defined as the cumulative use of a specific statin (atorvastatin, simvastatin, or rosuvastatin) for > 30 days prior to the index sepsis admission. We determined the association between statin and sepsis outcome by multivariate-adjusted Cox models and propensity score (PS)-matched analysis, using a 1:1:1 PS matching technique.

      Results

      A total of 52,737 patients with sepsis fulfilled the inclusion criteria, of which 1,855 were prescribed atorvastatin, 916 were prescribed simvastatin, and 732 were prescribed rosuvastatin. Compared with nonusers, simvastatin (hazard ratio [HR], 0.72; 95% CI, 0.58-0.90) and atorvastatin (HR, 0.78; 95% CI, 0.68-0.90) were associated with an improved 30-day survival, whereas rosuvastatin was not (HR, 0.87; 95% CI, 0.73-1.04). Using rosuvastatin as the reference, atorvastatin (HR, 0.79; 95% CI, 0.64-0.99) and simvastatin (HR, 0.77; 95% CI, 0.59-0.99) had superior effectiveness in preventing mortality.

      Conclusions

      Compatible with in vitro experimental findings, our results suggest that the drug-specific effect of statins on sepsis is not correlated to their lipid-lowering potency.

      Key Words

      Abbreviations:

      HR ( hazard ratio), ICD-9-CM ( International Classification of Diseases–9th Revision–Clinical Modification), LHID ( Longitudinal Health Insurance Database), PS ( propensity score)
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      Linked Article

      • Effect of Statins on Sepsis Outcome in a Population-Based Cohort Study
        CHESTVol. 154Issue 3
        • In Brief
          We read with great interest the publication by Lee et al1 in CHEST (April 2018) about the effect of statins on sepsis outcome in a population-based cohort study. Their work revealed that, compared with statin nonusers, atorvastatin and simvastatin users were associated with significant improvements in 30-day mortality rates.1 Moreover, atorvastatin and simvastatin were superior to rosuvastatin in preventing mortality, possibly because both had more potent in vitro antibacterial effects than rosuvastatin.
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      • Response
        CHESTVol. 154Issue 3
        • In Brief
          We appreciate the interest shown in our study1 by Ko et al and thank them for their insightful comments. The survival advantage of simvastatin users during sepsis, as observed in our study, was compatible with the superior antibacterial activity to Staphylococcus aureus observed in the Ko et al in vivo study. However, Ko et al described that the serum level of simvastatin could not reach the minimal inhibitory concentration in patients taking oral simvastatin and refuted the potential benefit from the statin’s antibacterial effect.
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