Background:

Pneumonia is associated with an inflammatory cascade that adversely affects clinical outcomes. As statins mitigate inflammation, they may improve pneumonia outcomes. We conducted a systematic review and meta–analysis of the effects of statin treatment on mortality after pneumonia to explore this association.

Methods:

Relevant studies were identified by serial searches of eight databases (MEDLINE, EMBASE, BIOSIS, the Cochrane CENTRAL Register of Controlled Trials, the Cochrane Database of Reviews of Effectiveness, Cambridge Scientific Abstracts, Biosis and Scopus) from inception to November 2011. Additional studies were identified through hand searches of bibliographies, pharmaceutical manufacturer websites, clinicaltrials.gov and content experts. three investigators independently selected eligible studies from original research reporting the effects of statin use on mortality after pneumonia. 2 investigators independently performed article abstraction and quality assessment. Studies were eligible if they included participants >18 years of age with bacterial pneumonia; current statin users; and reported mortality after pneumonia. The primary measure of pooled treatment effect was all–cause mortality in patients receiving statins compared to control. All statistical tests were two–tailed and were based on a random–effects model using the method described by DerSimonian–Laird. Data management and statistical analyses were performed using STATA MP Version 11 (Stata Corporation, College Station, TX); P less than 0.05 was considered statistically significant.

Results:

Of 491 citations identified, 13 studies (2 case–control; 10 cohort and 1 randomized controlled trial) involving 254,950 patients met eligibility criteria. Pooled unadjusted data showed that statin use was associated with decreased mortality after pneumonia (OR 0.62, 95% confidence interval [CI] 0.54 – 0.71, P <0.001). Pooling of adjusted data also showed a protective effect of statins against mortality after pneumonia (OR 0.66, 95% CI 0.55–0.79, P <0.001). Heterogeneity in the pooled data was resolved by the variable intervals at which mortality was reported. However, subgroup analysis stratifying the included studies by pneumonia severity, clinical measures infrequently available for adjustment (e.g. nursing home status, bacteremia), and healthy–user covariates (e.g. vaccination status) weakened the strength of the association between statin use and mortality after pneumonia. Further, no significant effect of statin use on death after pneumonia was observed in the three prospective cohort studies and single(underpowered) randomized controlled study.

Conclusions:

Statin use is associated with a reduction in mortality after pneumonia. However, this effect weakens in important subgroups and may be related to residual confounding, healthy–user bias or methodological limitations inherent to meta–analysis. A randomized controlled study is necessary to fully understand the effect of statins on pneumonia.

Figure 1Pooled Odds Ratio of Unadjusted Mortality From Pneumonia In Statin Users

Figure 2Pooled Adjusted Mortality From Pneumonia In Statin Users