The Effect of Statins on Mortality in Septic Patients: A Meta-Analysis of Randomized Controlled Trials (original) (raw)
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Impact of Statins in Outcomes of Septic Patients: A Systematic Review
Postgraduate Medicine, 2014
The pleiotropic effects of statins have prompted considerable research in fields other than cardiovascular disease. We reviewed the literature aiming to summarize and critically evaluate the current evidence about the potential use of statins in sepsis. Materials and Methods: We searched the Pubmed, SciELO, and Cochrane electronic databases from inception through November 1, 2013, for randomized controlled trials (RCTs) and cohort studies that examined the association between statin use (upon hospital admission or previous users) and the risk or outcome of sepsis. Data on study characteristics, measurement of statin use, and outcomes (adjusted for potential confounders) were extracted. We structured our review according to the Principles of Reporting in Systematic Reviews and Meta-Analysis criteria. Quality assessment of cohort studies was performed using the Ottawa-Newcastle Scale. Results: Twenty-three cohort studies and 5 RCTs were eligible, comprising 42 549 statin users and 54 201 non-statin users, from 1995 to 2013. The populations included varied from patients admitted to general wards or intensive care units with bacterial infections, community-acquired pneumonia, ventilatorassociated pneumonia, bacteremia, or sepsis, to outpatients with chronic kidney disease or established cardiovascular disease. Overall, 16 studies reported a benefit from statin use in morbidity or mortality outcomes (range of adjusted odds ratio, 0.06-0.62; α = 0.05). The remaining 12 studies found no protective effect associated with statin use upon hospital admission or previous users. Among the 5 RCTs, none demonstrated a reduction in mortality. Conclusion: There is insufficient evidence to support the use of statins in patients with sepsis, as the existing studies failed to prove a consistent mortality benefit. More clinical trials are warranted to provide more conclusive knowledge and ultimately change clinical practice.
Systematic review of statins in sepsis: There is no evidence of dose response
Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine, 2016
Sepsis is a common cause of morbidity and mortality and is associated with significant costs to the healthcare organizations. We performed a systematic review and meta-analysis to assess whether high or low-dose statin therapy improved mortality in patients with sepsis. The trials analyzed in this study were multicenter or single center randomized control studies using statins for sepsis in a hospital setting. The patients included were adults with suspected or confirmed infection. This study found eight randomized controlled trials where participants were given either a statin or placebo daily for 14-28 days, the duration of their illness, or until their death or discharge, which ever occurred first. This meta-analysis measured the effect of statin therapy on in hospital and 28 days mortality. In unselected patients, there was no demonstrable difference in the 28 days mortality (relative risk [RR] 0.88 95% confidence interval [CI], 0.70-1.12 and P = 0.16). There was also no signifi...
Reduction in Mortality Associated with Statin Therapy in Patients with Severe Sepsis
Pharmacotherapy, 2009
Study Objective. To evaluate the effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) on mortality in patients with severe sepsis. Design. Retrospective cohort study. Setting. Intensive care unit (ICU) of an academic medical center. Patients. One hundred eighty-eight patients aged 40 years or older with a diagnosis of severe sepsis and an ICU stay between January 1, 2005, and December 31, 2006. Measurements and Main Results. Patient demographic data, statin use, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores at the time of sepsis diagnosis were collected from the patient database. We used a multivariable logistic regression model to evaluate the association between statin use and in-hospital all-cause mortality after controlling for age, sex, and severity of illness. Of the 188 patients who met our inclusion criteria, 60 (32%) had statin exposure. Patients receiving statins were similar in age, sex, and APACHE II scores to those not receiving statins. In the univariable comparison, the statin group had a 35% relative reduction in mortality compared with the nonstatin group (mortality rate 31.7% vs 48.4%, p=0.040). Most of the mortality reduction attributed to statins occurred in patients with APACHE II scores higher than 24 (mortality rate 32.3% vs 57.5%, p=0.031), with a minimal mortality difference in patients with APACHE II scores of 24 or lower (31% vs 36.4%, p=0.810). In the multivariable regression model, statin use had a protective effect (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.21-0.84, p=0.014), whereas increasing age (OR 1.03, 95% CI 1.01-1.06, p=0.013) and higher APACHE II score (OR 1.11, 95% CI 1.05-1.18, p=0.001) were associated with increased mortality. Conclusion. The use of statins was associated with a protective effect in patients with severe sepsis, as demonstrated by a significant reduction in mortality compared with patients not receiving statins.
A Population-Based Cohort Study on the Drug-Specific Effect of Statins on Sepsis Outcome
Chest, 2017
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. 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. 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...
Statins for sepsis: a critical and updated review
Clinical Microbiology and Infection, 2009
There is increasing discussion of a potential role for statins in the management of sepsis. A search of PubMed, Embase, Scopus and the Cochrane Library databases was performed by combining the terms ‘statins’, ‘infection’, ‘sepsis’, ‘bacteraemia’, ‘pneumonia’, and ‘ICU infections’. A total of 22 studies were retrieved, which included 177 260 people and compared clinical outcomes between 51 193 statin users and 126 067 non-statin users. Nineteen were cohort studies (seven prospective and 12 retrospective), two were retrospective case–control studies, and one was a randomized controlled study. Nine studies examined the use of statins in sepsis, four in community-acquired pneumonia (CAP), three in bacteraemia, and three in post-operative patients. Mortality data were presented in 15 studies; in ten, mortality was lower among statin users (three of six sepsis studies, five of six CAP studies, and two of three bacteraemia studies). In four studies, there was no difference in mortality (two of six sepsis studies, one of six CAP studies, and one of three bacteraemia studies) and in one study there was increased mortality among septic intensive-care unit patients receiving statins. Five of the nine studies that examined the risk of developing sepsis/infection as a primary outcome (six of nine sepsis studies and all studies in the postoperative setting) found a decreased risk among statin users, whereas the remaining studies found no difference. Irrespective of their design (matched vs. non-matched), the majority of the studies suggested that statins have a beneficial effect on the outcome of infection; however, their observational design does not allow us to draw firm conclusions. The clinical benefit of statin therapy in sepsis remains to be determined by ongoing randomized controlled trials.
Effectiveness of Statins in Reducing the Rate of Severe Sepsis: A Retrospective Evaluation
Pharmacotherapy, 2007
To determine whether use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is associated with a reduced rate of severe sepsis, and to further characterize the effect of statins on the frequency of organ dysfunction in patients with severe sepsis. Design. Retrospective cohort study. Setting. University-associated teaching hospital. Patients. Fifty-three patients admitted with sepsis; 16 were receiving statins and 37 were not receiving statins (controls) before admission.
Prior Statin Therapy Is Associated With a Decreased Rate of Severe Sepsis
Circulation, 2004
Background— Statins have anti-inflammatory properties that are independent of their lipid-lowering abilities. We hypothesized that statin therapy before the onset of an acute bacterial infection may have a protective effect against severe sepsis. The aim of this study was to determine whether patients treated with statins develop severe sepsis less frequently. Methods and Results— In this prospective observational cohort study, consecutive patients admitted with presumed or documented acute bacterial infection were enrolled. The primary outcomes were the rate of severe sepsis and intensive care unit (ICU) admission. Of the 361 patients enrolled, 82 (22.7%) were treated with statins before their admission. Both groups had a similar severity of illness on admission. Severe sepsis developed in 19% of patients in the no-statin group and in only 2.4% of the statin group ( P <0.001). Statin treatment was associated with a relative risk of developing severe sepsis of 0.13 (95% CI, 0.03 ...
2011
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 [6-14] 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.