Pleiotropic effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in pulmonary diseases: A comprehensive review

Krishna, Rama K.; Issa, Omar; Saha, Debjit; Macedo, Francisco; Correal, Barbara; Santana, Orlando

doi:10.1016/j.pupt.2014.08.006

Cited by 9 publications

(8 citation statements)

References 85 publications

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“…Besides a proven effect on reducing cardiovascular disease by treating hypercholesterolaemia, they have other pleiotropic anti-inflammatory effects as well. 7 8 In the lung, statins have an effect on bronchial remodelling, emphysema development and recruitment of inflammatory cells. Effects are systemically observed on various biomarkers and cytokines such as high-sensitivity C reactive protein (hsCRP), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor α (TNF-α).…”

Section: Introductionmentioning

confidence: 99%

Statins and morbidity and mortality in COPD in the COMIC study: a prospective COPD cohort study

et al. 2016

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BackgroundBoth chronic inflammation and cardiovascular comorbidity play an important role in the morbidity and mortality of patients with chronic obstructive pulmonary disease (COPD). Statins could be a potential adjunct therapy. The additional effects of statins in COPD are, however, still under discussion. The aim of this study is to further investigate the association of statin use with clinical outcomes in a well-described COPD cohort.Methods795 patients of the Cohort of Mortality and Inflammation in COPD (COMIC) study were divided into statin users or not. Statin use was defined as having a statin for at least 90 consecutive days after inclusion. Outcome parameters were 3-year survival, based on all-cause mortality, time until first hospitalisation for an acute exacerbation of COPD (AECOPD) and time until first community-acquired pneumonia (CAP). A sensitivity analysis was performed without patients who started a statin 3 months or more after inclusion to exclude immortal time bias.ResultsStatin use resulted in a better overall survival (corrected HR 0.70 (95% CI 0.51 to 0.96) in multivariate analysis), but in the sensitivity analysis this association disappeared. Statin use was not associated with time until first hospitalisation for an AECOPD (cHR 0.95, 95% CI 0.74 to 1.22) or time until first CAP (cHR 1.1, 95% CI 0.83 to 1.47).ConclusionsIn the COMIC study, statin use is not associated with a reduced risk of all-cause mortality, time until first hospitalisation for an AECOPD or time until first CAP in patients with COPD.

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Section: Introductionmentioning

confidence: 99%

Statins and morbidity and mortality in COPD in the COMIC study: a prospective COPD cohort study

et al. 2016

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“…This injury could result from an altered host immune response after mechanical stretch [3]. Using statin therapy to protect patients with lung injury could therefore be a reasonable strategy, as these drugs could abate the host inflammatory response to infection [21], especially within the lungs [6]. This study revealed that statin use was associated with improved 28-day survival and in-hospital survival.…”

Section: Discussionmentioning

confidence: 86%

“…In addition to lowering cholesterol, statins exert pleiotropic effects [6][7][8][9] such as anti-inflammatory, antioxidant, and immunomodulatory effects, especially in the context of pulmonary disorders [22].…”

Section: Discussionmentioning

confidence: 99%

“…Statins, also known as 3-hydroxy-3 methylblycel coenzyme A (HMG-CoA) reductase inhibitors, exert pleiotropic effects in addition to their lipid-lowering effects in the context of coronary artery disease [4] and ischemic stroke [5] prophylaxes. Studies in vitro and in vivo have shown that statins can provide additional protective effects, including the reduction in inflammation, immunomodulation, antimicrobial effects, improved endothelial cell function and antithrombotic actions [6][7][8][9][10]. In pneumonia patients, current statin use was associated with decreased mortality [11] .…”

Section: Introductionmentioning

confidence: 99%

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Statin Use Is Associated With Reduced Mortality On Mechanically Ventilated Patients: A Retrospective Propensity-Matched Analysis Of MIMIC-III Database

Lin

Chen

et al. 2020

Preprint

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Objective: Mechanical ventilation can cause injury and inflammatory disorders in the lungs of critically ill patients. We sought to determine whether statin treatment has a protective effect on the outcome of these patients. Methods: A retrospective observational study of ICU patients from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Information on ventilated patients was analyzed using data from the MIMIC-III database. The non-statin cohort was selected using 1:1 propensity matching with the statin cohort by age, sex, severity scores and 29 other variables. Compared with nonusers, the use of statins was associated with improved 28-day survival in the unmatched cohort (HR 0.85 95% CI 0.80~0.90) and matched cohort (HR 0.72 95% CI 0.67~0.77). Statin use was also associated with improved in-hospital survival in both the unmatched cohort (HR 0.90, 95% CI 0.85~0.95) and the matched cohort (HR 0.75 95% CI 0.70~0.80). In the multivariate Cox model, the use of statins was also associated with an improvement in 28-day survival in the unmatched cohort (HR 0.73 95% CI 0.68～0.77) and in the matched cohort (HR 0.73 95% CI 0.68~0.78). The use of statins was associated with longer ICU length of stay (LOS), shorter ventilator-free days (VFDs) and fewer model for end-stage liver disease score (MELD) in the matched cohort. The subgroup analysis results showed improved 28-day survival, but this improvement was not observed in patients with pneumonia, obesity, septicemia or acute respiratory failure. Conclusions: In a population of mechanically ventilated patients, the use of statins may be associated with reduced mortality.

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“…The pleiotropic effects of statins through induction of endothelial nitric oxide (NO) expression as well as anti-inflammatory and antiproliferative mechanisms possibly confer various clinical advantages beyond the reduction of serum cholesterol levels 8 9 . Since statins have been suggested as potential drugs for PAH treatment 10 , we assessed the impact of statin therapy on multiple parameters in PAH in this systematic review and meta-analysis.…”

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confidence: 99%

Efficacy of Statin Therapy in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis

Rysz-Górzyńska

Gluba-Brzózka

Sahebkar

et al. 2016

Sci Rep

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Since the evidence regarding statin therapy in PAH has not been conclusive, we assessed the impact of statin therapy in PAH through a systematic review and meta-analysis of available studies. We searched selected databases up to August 1, 2015 to identify the studies investigating the effect of statin administration on PAH. Meta-analysis was performed using either a fixed-effects or random-effect model according to I2 statistic. Meta-analysis of 8 studies with 665 patients did not suggest any significant improvement in 6-min walking distance (6MWD) by statin therapy (weighed mean difference [WMD]: −6.08 m, 95% confidence interval [CI]: −25.66, 13.50, p = 0.543; Q = 8.41, I2 = 28.64%). Likewise, none of the other indices including pulmonary arterial pressure (WMD: −0.97 mmHg, 95%CI: −4.39, 2.44, p = 0.577; Q = 14.64, I2 = 79.51%), right atrial pressure (WMD: 1.01 mmHg, 95%CI: −0.93, 2.96, p = 0.307; Q = 44.88, I2 = 95.54%), cardiac index (WMD: 0.05 L/min/m2, 95%CI: −0.05, 0.15, p = 0.323; Q = 3.82, I2 = 21.42%), and pulmonary vascular resistance (WMD: −1.42 dyn*s/cm5, 95%CI: −72.11, 69.27, p = 0.969; Q = 0.69, I2 = 0%) was significantly altered by statin therapy. In conclusion, the results of the meta-analysis did not show a statistically significant effect of statin therapy in the improvement of 6MWD, pulmonary arterial pressure, right atrial pressure, cardiac index and pulmonary vascular resistance.

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Pleiotropic effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in pulmonary diseases: A comprehensive review

Cited by 9 publications

References 85 publications

Statins and morbidity and mortality in COPD in the COMIC study: a prospective COPD cohort study

Statins and morbidity and mortality in COPD in the COMIC study: a prospective COPD cohort study

Statin Use Is Associated With Reduced Mortality On Mechanically Ventilated Patients: A Retrospective Propensity-Matched Analysis Of MIMIC-III Database

Efficacy of Statin Therapy in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis

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