Statins and associated risk of pneumonia: A systematic review and meta-analysis of observational studies

School of Medicine, University of East Anglia, Norwich, NR4 7TJ, UK.
European Journal of Clinical Pharmacology (Impact Factor: 2.97). 11/2011; 68(5):747-55. DOI: 10.1007/s00228-011-1159-4
Source: PubMed


Statins have potential anti-inflammatory effects, but the association between statin use and lower incidence of pneumonia is unclear. We have therefore performed a systematic review on the risk of pneumonia in statin users versus non-users.
MEDLINE and EMBASE were searched in December 2010 for controlled observational studies that reported on the risk of pneumonia in statin users. We performed a random effects meta-analysis and assessed heterogeneity using the I² statistic.
A total of 451 citations were screened, and ultimately nine studies (4 case-control, 4 retrospective cohort, 1 prospective cohort) with more than 3 million participants were included in the meta-analysis. Pooled analysis of seven studies that reported unadjusted data failed to show a significantly reduced risk of pneumonia [odds ratio (OR) 0.94, 95% confidence interval (CI) 0.84-1.06, p = 0.33, I² = 79%] in statin users as compared to non-users. However, a significant reduction in the likelihood of pneumonia associated with statin use (n = 8 studies, OR 0.85, 95% CI 0.75-0.97, p = 0.02, I² = 81%) was found in the meta-analysis of adjusted data. Both analyses were limited by substantial statistical heterogeneity. Sensitivity analysis failed to fully clarify the source of heterogeneity, but cohort studies seemed to be less heterogenous (n = 5 studies, OR 0.92, 95% CI 0.84-1.01, I² = 43%).
Our findings indicate that the purported benefit of statins in preventing pneumonia is inconsistent, and of low magnitude, with upper bounds of the confidence interval being close to null. In view of the substantial statistical and clinical heterogeneity in the dataset, there is no convincing evidence to support the therapeutic application of statins for reducing the risk of pneumonia.

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    • "A recently published meta-analysis of observational studies also found a similar reduction in the likelihood of pneumonia associated with statin use [122], in line with randomized findings from the Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial [123]. Statin use may be a surrogate marker for better health which may confound the observed association with pneumonia [124]. "
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    ABSTRACT: Efficacy of statins has been extensively studied, with much less information reported on their unintended effects. Evidence from randomized controlled trials (RCTs) on unintended effects is often insufficient to support hypotheses generated from observational studies. We aimed to systematically assess unintended effects of statins from observational studies in general populations with comparison of the findings where possible with those derived from randomized trials. Medline (1998 to January 2012, week 3) and Embase (1998 to 2012, week 6) were searched using the standard BMJ Cohort studies filter. The search was supplemented with reference lists of all identified studies and contact with experts in the field. We included prospective studies with a sample size larger than 1,000 participants, case control (of any size) and routine health service linkage studies of over at least one year duration. Studies in subgroups of patients or follow-up of patient case series were excluded, as well as hospital-based cohort studies. Ninety studies were identified, reporting on 48 different unintended effects. Statins were associated with lower risks of dementia and cognitive impairment, venous thrombo-embolism, fractures and pneumonia, but these findings were attenuated in analyses restricted to higher quality studies (respectively: OR 0.74 (95% CI 0.62 to 0.87); OR 0.92 (95% CI 0.81 to 1.03); OR 0.97 (95% CI 0.88 to 1.05); OR 0.92 (95% CI 0.83 to 1.02)); and marked heterogeneity of effects across studies remained. Statin use was not related to any increased risk of depression, common eye diseases, renal disorders or arthritis. There was evidence of an increased risk of myopathy, raised liver enzymes and diabetes (respectively: OR 2.63 (95% CI 1.50 to 4.61); OR 1.54 (95% CI 1.47 to 1.62); OR 1.31 (95% CI 0.99 to 1.73)). Our systematic review and meta-analyses indicate that high quality observational data can provide relevant evidence on unintended effects of statins to add to the evidence from RCTs. The absolute excess risk of the observed harmful unintended effects of statins is very small compared to the beneficial effects of statins on major cardiovascular events.
    BMC Medicine 03/2014; 12(1):51. DOI:10.1186/1741-7015-12-51 · 7.25 Impact Factor
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    • "Our analysis is in agreement with some recently published systematic reviews, but does have some important differences [48]–[49]. First, our meta-analysis did not find any publication bias in the prevention group to evaluate the role of statins in the development of pneumonia. Second, in contrast to the study by Chopra et al [49] we used meta-regression to explore sources of heterogeneity, examined the effect of publication bias using contour-enhanced funnel plot [59] and used a novel regression-based method to adjust the pooled estimate for publication bias. "
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    ABSTRACT: Emerging epidemiological evidence suggests that statins may reduce the risk of community-acquired pneumonia (CAP) and its complications. Performed a systematic review to address the role of statins in the prevention or treatment of CAP. Ovid MEDLINE, Cochrane, EMBASE, ISI Web of Science, and Scopus from inception through December 2011 were searched for randomized clinical trials, cohort and case-control studies. Two authors independently reviewed studies that examined the role of statins in CAP. Data about study characteristics, adjusted effect-estimates and quality characteristics was extracted. Eighteen studies corresponding to 21 effect-estimates (eight and 13 of which addressed the preventive and therapeutic roles of statins, respectively) were included. All studies were of good methodological quality. Random-effects meta-analyses of adjusted effect-estimates were used. Statins were associated with a lower risk of CAP, 0.84 (95% CI, 0.74-0.95), I(2) = 90.5% and a lower short-term mortality in patients with CAP, 0.68 (95% CI, 0.59-0.78), I(2) = 75.7%. Meta-regression did not identify sources of heterogeneity. A funnel plot suggested publication bias in the treatment group, which was adjusted by a novel regression method with a resultant effect-estimate of 0.85 (95% CI, 0.77-0.93). Sensitivity analyses using the rule-out approach showed that it is unlikely that the results were due to an unmeasured confounder. Our meta-analysis reveals a beneficial role of statins for the risk of development and mortality associated with CAP. However, the results constitute very low quality evidence as per the GRADE framework due to observational study design, heterogeneity and publication bias.
    PLoS ONE 01/2013; 8(1):e52929. DOI:10.1371/journal.pone.0052929 · 3.23 Impact Factor

  • European Journal of Clinical Pharmacology 12/2011; 68(5):889-90. DOI:10.1007/s00228-011-1190-5 · 2.97 Impact Factor
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