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Autoimmunity Reviews Apr 2016Efficacy and safety of statin therapy in patients with systemic lupus erythematosus (SLE) is controversial. The aim of this meta-analysis was to evaluate whether statin... (Meta-Analysis)
Meta-Analysis Review
Statin impact on disease activity and C-reactive protein concentrations in systemic lupus erythematosus patients: A systematic review and meta-analysis of controlled trials.
BACKGROUND AND PURPOSE
Efficacy and safety of statin therapy in patients with systemic lupus erythematosus (SLE) is controversial. The aim of this meta-analysis was to evaluate whether statin therapy affects SLE disease activity and systemic inflammation (C-reactive protein, CRP) according to the evidence from controlled clinical trials.
EXPERIMENTAL APPROACH
A systematic review followed by a bibliographic search in Medline and SCOPUS (up to March 2015) was performed. Quantitative data synthesis was performed using a random-effects model and the generic inverse variance weighting method. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI).
KEY RESULTS
Meta-analysis of five controlled trials reporting statin impact on SLE disease activity did not suggest any significant effect of statin therapy on SLEDAI. Evaluation of seven controlled trials with reported effects on CRP levels suggested a significant reduction of plasma CRP concentrations in patients with SLE independent of the treatment duration. The effect size on plasma CRP concentrations was significant with lipophilic (atorvastatin) but not hydrophilic (pravastatin and rosuvastatin) statins.
CONCLUSION AND IMPLICATIONS
The present results suggest that statin therapy is likely to be safe in patients with SLE. In addition, statin-treated SLE patients may benefit from CRP reduction in terms of managing severe cardiovascular complications associated with the disease.
Topics: C-Reactive Protein; Controlled Clinical Trials as Topic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lupus Erythematosus, Systemic
PubMed: 26747436
DOI: 10.1016/j.autrev.2015.12.007 -
Cancer Causes & Control : CCC Oct 2020The link between lipid-stabilizing medications and epithelial ovarian carcinogenesis is incompletely understood. Statins may reduce ovarian cancer risk, but results are... (Meta-Analysis)
Meta-Analysis
PURPOSE
The link between lipid-stabilizing medications and epithelial ovarian carcinogenesis is incompletely understood. Statins may reduce ovarian cancer risk, but results are inconclusive.
METHODS
We conducted a systematic review and meta-analysis of studies reporting associations between statin use and ovarian cancer risk in PubMed. Summary risk ratios (RRs) and confidence intervals (CIs) were calculated. Subgroup analyses by cancer histotype, statin class (lipo- or hydrophilic) and duration of statin use were conducted. Use of individual statins in populations was assessed to determine population-specific differences in statin types.
RESULTS
Nine studies with 435,237 total women were included (1 randomized controlled trial (RCT); 4 prospective; 4 case-control). Statin use was associated with a reduced risk of ovarian cancer (RR 0.87, 95% CI 0.74-1.03) and risk was significantly reduced in populations with low pravastatin use (RR 0.83, 95% CI 0.70-0.99). Risk estimates varied by statin class (3 studies; lipophilic: RR 0.88, 95% CI 0.69-1.12; hydrophilic: RR 1.06, 95% CI 0.72-1.57) and cancer histotype (3 studies; serous: RR 0.95, 95% CI 0.69-1.30; clear cell: RR 1.17, 95% CI 0.74-1.86). Long-term use was associated with a reduced risk of ovarian cancer (RR 0.77, 95% CI 0.54-1.10) that further reduced when pravastatin use was low (RR 0.68, 95% CI 0.46-1.01). Between-study heterogeneity was high overall and in subgroups (I > 60%).
CONCLUSION
Statins may be associated with a reduced risk of ovarian cancer, but the effect likely differs by individual statin, duration of use and cancer histotype. Additional well-powered studies are needed to elucidate important subgroup effects.
Topics: Case-Control Studies; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ovarian Neoplasms; Prospective Studies; Randomized Controlled Trials as Topic; Risk
PubMed: 32685996
DOI: 10.1007/s10552-020-01327-8 -
American Journal of Kidney Diseases :... Jun 2016The effects of statin administration on kidney disease outcomes remain controversial. We undertook a systematic review and meta-analysis to assess the efficacy of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The effects of statin administration on kidney disease outcomes remain controversial. We undertook a systematic review and meta-analysis to assess the efficacy of statins on kidney outcomes.
STUDY DESIGN
We conducted a meta-analysis of randomized controlled trials (RCTs) using MEDLINE (1946 to August 31, 2015), EMBASE (1966 to August 31, 2015), and the Cochrane Library database (no date restriction).
SETTING & POPULATION
Adults who were not receiving dialysis, for whom kidney disease outcomes were reported.
SELECTION CRITERIA FOR STUDIES
RCTs in which statins were given for at least 6 months and kidney outcomes were measured.
INTERVENTION
Statins versus control, including placebo, usual care, and different types or doses of statins.
OUTCOMES
Kidney failure events, rate of change in estimated glomerular filtration rate (eGFR) per year, change in proteinuria or albuminuria, and, in patients with chronic kidney disease, major cardiovascular events.
RESULTS
57 eligible studies with 143,888 participants were included. Statin treatment did not produce an apparent beneficial effect for kidney failure events (OR, 0.98; 95% CI, 0.87-1.10; P=0.7) or end-stage renal disease events (OR, 0.98; 95% CI, 0.90-1.07; P=0.7). However, mean difference for rate of decline in eGFR (0.41 [95% CI, 0.11-0.70] mL/min/1.73m(2) per year slower in statin recipients) and standardized mean difference for change in proteinuria or albuminuria (-0.65 [95% CI, -0.94 to -0.37] standard deviation units, statin recipients vs controls) were statistically significant. In addition, statin therapy significantly reduced the risk for cardiovascular events (OR, 0.69; 95% CI, 0.61-0.79; P<0.001) in patients with chronic kidney disease.
LIMITATIONS
Inclusion of several post hoc analyses from large RCTs and substantial heterogeneity in secondary outcome analyses.
CONCLUSIONS
Statin therapy does not reduce the risk for kidney failure events in adults not receiving dialysis for whom kidney disease outcomes were reported, but may modestly reduce proteinuria and rate of eGFR decline.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Treatment Outcome
PubMed: 26905361
DOI: 10.1053/j.ajkd.2016.01.016 -
BMC Gastroenterology Mar 2021There is increased interest in the therapeutic use of statins in cirrhosis, but preferred statin and safety outcomes are still not well known. In this systematic review...
BACKGROUND/AIMS
There is increased interest in the therapeutic use of statins in cirrhosis, but preferred statin and safety outcomes are still not well known. In this systematic review we aimed to address pharmacokinetics (PK), safety, and effects on cardiovascular (CV) outcomes of statins in cirrhosis.
METHODS
Our systematic search in several electronic databases and repositories of two regulatory bodies up to 2020-06-11 yielded 22 articles and 2 drug monographs with relevant data.
RESULTS
Rosuvastatin and pitavastatin showed minimal PK changes in Child-Pugh A cirrhosis. Only rosuvastatin was assessed in a repeated dosing PK study. Atorvastatin showed pronounced PK changes in cirrhosis. No PK data was found for simvastatin, the most commonly used statin in cirrhosis trials. There was insufficient data to assess CV effects of statins in cirrhosis. Clinical trials in cirrhosis were limited to simvastatin, atorvastatin, and pravastatin. In patients taking simvastatin 40 mg, pooled frequency of rhabdomyolysis was 2%, an incidence 40-fold higher than that reported in non-cirrhosis patients, while this was no rhabdomyolysis observed in patients on simvastatin 20 mg, atorvastatin 20 mg, or pravastatin 40 mg. Drug-induced liver injury was of difficult interpretation due to co-existence of muscle damage. No overt liver failure was reported.
CONCLUSIONS
Simvastatin 40 mg should be avoided in decompensated cirrhosis. Safety data on simvastatin 20 mg or other statins are based on small study sample size. This rarity of evidence combined with lack of data in dose adjustment methods in cirrhosis is a barrier for using statins for CV indications or for investigational use for liver indications.
Topics: Atorvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver Cirrhosis; Pravastatin; Simvastatin
PubMed: 33726685
DOI: 10.1186/s12876-021-01704-w -
American Journal of Obstetrics and... Feb 2022There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying...
There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying disease pathophysiology. Molecular targets of candidate treatments include oxidative stress, antiangiogenic factors, and the angiotensin, nitric oxide, and proinflammatory pathways. The proposed treatments undergoing preclinical and clinical trial evaluation are thought to act on placental or endothelial disease or both. Most have adopted the pragmatic strategy of repurposing drugs. Of all the therapeutic agents proposed, pravastatin has received the most interest. There are preclinical studies showing that it has pleiotropic actions that favorably impact on multiple molecular targets and can resolve a preeclampsia phenotype in many animal models. An early phase clinical trial suggests that it may have therapeutic activity. Several large prevention trials are planned or ongoing and, when completed, could definitively address whether pravastatin can prevent preeclampsia. Proton-pump inhibitors, metformin, and sulfasalazine are other drugs with preclinical evidence of multiple molecular actions that could resolve the pathophysiology of preeclampsia. These agents are also currently being evaluated in clinical trials. There have been many recent preclinical studies identifying the potential of numerous natural compounds to treat preeclampsia, such as plant extracts and micronutrients that have potent anti-inflammatory or antioxidant activity. Recent preclinical studies have also proposed novel molecular-targeted strategies, such as monoclonal antibodies targeting tumor necrosis factor alpha, placental growth factor, and short interfering RNA technology, to silence the gene expression of soluble fms-like tyrosine kinase-1 or angiotensinogen. Other treatment approaches that have transitioned to human trials (ranging from single-arm to phase III trials that have been completed or are ongoing) include folic acid, nitric oxide donors (such as L-arginine), recombinant antithrombin III, digoxin immune antigen-binding fragment, and melatonin. There have been case series showing the removal of circulating soluble fms-like tyrosine kinase-1 may help stabilize the disease and prolong pregnancy. Interestingly, there are case reports suggesting that monoclonal antibody eculizumab (complement inhibitor) may have therapeutic potential. If new agents are discovered that are proven to be effective in preventing or treating preeclampsia, the potential to improve global maternal and perinatal health will be significant.
Topics: Antibodies, Monoclonal; Antioxidants; Antithrombin III; Biological Products; Blood Component Removal; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Metformin; Micronutrients; Placenta Growth Factor; Plant Extracts; Pravastatin; Pre-Eclampsia; Pregnancy; Proton Pump Inhibitors; RNA, Small Interfering; Recombinant Proteins; Sulfasalazine; Vascular Endothelial Growth Factor Receptor-1
PubMed: 32946849
DOI: 10.1016/j.ajog.2020.09.014 -
Thrombosis and Haemostasis Aug 2015D-dimers, specific breakdown fragments of cross-linked fibrin, are generally used as circulating markers of activated coagulation. Statins influence haemostatic factors,... (Meta-Analysis)
Meta-Analysis Review
D-dimers, specific breakdown fragments of cross-linked fibrin, are generally used as circulating markers of activated coagulation. Statins influence haemostatic factors, but their effect on plasma D-dimer levels is controversial. Therefore, the aim of this meta-analysis was to evaluate the association between statin therapy and plasma D-dimer levels. We searched PubMed, Web of Science, Cochrane Library, Scopus and EMBASE (up to September 25, 2014) to identify randomised controlled trials (RCTs) investigating the impact of statin therapy on plasma D-dimer levels. Two independent reviewers extracted data on study characteristics, methods and outcomes. Meta-analysis of data from nine RCTs with 1,165 participants showed a significant effect of statin therapy in reducing plasma D-dimer levels (standardised mean difference [SMD]: -0.988 µg/ml, 95 % confidence interval [CI]: -1.590 - -0.385, p=0.001). The effect size was robust in sensitivity analysis and omission of no single study significantly changed the overall estimated effect size. In the subgroup analysis, the effect of statins on plasma D-dimer levels was significant only in the subsets of studies with treatment duration ≥ 12 weeks (SMD: -0.761 µg/ml, 95 %CI: -1.163- -0.360; p< 0.001), and for lipophilic statins (atorvastatin and simvastatin) (SMD: -1.364 µg/ml, 95 % CI: -2.202- -0.526; p=0.001). Hydrophilic statins (pravastatin and rosuvastatin) did not significantly reduce plasma D-dimer levels (SMD: -0.237 µg/ml, 95 %CI: -1.140-0.665, p=0.606). This meta-analysis of RCTs suggests a decrease of plasma D-dimer levels after three months of statin therapy, and especially after treatment with lipophilic statins. Well-designed trials are required to validate these results.
Topics: Anticoagulants; Biomarkers; Blood Coagulation; Dyslipidemias; Fibrin Fibrinogen Degradation Products; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome
PubMed: 26017749
DOI: 10.1160/TH14-11-0937 -
Neurosurgery Jul 2023The exacerbation of neurological outcomes often occurs in aneurysmal subarachnoid hemorrhage (aSAH). Statins have been commonly used for aSAH; however, there is lack of... (Meta-Analysis)
Meta-Analysis
Impacts of Statin Therapy Strategies on Incidence of Ischemic Cerebrovascular Events in Patients With Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Bayesian Network Meta-Analysis.
BACKGROUND
The exacerbation of neurological outcomes often occurs in aneurysmal subarachnoid hemorrhage (aSAH). Statins have been commonly used for aSAH; however, there is lack of evidence of the pharmacological efficacy of different dosages and types of statins.
OBJECTIVE
To apply the Bayesian network meta-analysis to analyze the optimal dosage and type of statins for the amelioration of ischemic cerebrovascular events (ICEs) in patients with aSAH.
METHODS
We developed the Bayesian network meta-analysis and systemic review to analyze the effects of statins on functional prognosis and the impacts of optimal dosage and type of statins on ICEs in patients with aSAH. The outcome variables of the analysis were the incidence of ICEs and functional prognosis.
RESULTS
A total of 2569 patients with aSAH across 14 studies were included. Analysis of 6 randomized controlled trials showed that statin use significantly improved functional prognosis in patients with aSAH (risk ratio [RR], 0.73; 95% CI, 0.55-0.97). Statins significantly reduced the incidence of ICEs (RR, 0.78; 95% CI, 0.67-0.90). Pravastatin (40 mg/d) decreased the incidence ICEs compared with placebo (RR, 0.14; 95% CI, 0.03-0.65) and was ranked the most effective, presenting with a significantly lower rate of the incidence ICEs than the worst-ranked simvastatin (40 mg/d) (RR, 0.13; 95% CI, 0.02-0.79).
CONCLUSION
Statins could significantly diminish the incidence of ICEs and enhance functional prognosis in patients with aSAH. Various types and dosages of statins show distinct efficacies.
Topics: Humans; Subarachnoid Hemorrhage; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Bayes Theorem; Network Meta-Analysis; Vasospasm, Intracranial
PubMed: 36794961
DOI: 10.1227/neu.0000000000002392 -
Drugs Jun 2016The aim of this study was to ascertain the effect size of statins in modulating plasma uric acid concentrations. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The aim of this study was to ascertain the effect size of statins in modulating plasma uric acid concentrations.
DATA SOURCES
A search was undertaken of the MEDLINE, SCOPUS, Web of Science and Google Scholar electronic databases.
STUDY SELECTION
Studies meeting the following criteria were included: (i) randomized controlled trials with either a parallel or crossover design; (ii) investigated the impact of statin therapy on plasma uric acid concentrations; and (iii) presentation of sufficient information on uric acid values at baseline and at the end of follow-up in each group, or presenting the net change.
DATA SYNTHESIS
The present meta-analysis suggested a significant reduction in plasma uric acid levels following statin therapy; however, this does not seem to be a class effect as subgroup analysis revealed a significant reduction with atorvastatin and simvastatin only, and not with pravastatin and rosuvastatin.
CONCLUSIONS
Atorvastatin and simvastatin, but not the other statins, can reduce serum uric acid levels.
Topics: Atorvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperuricemia; Randomized Controlled Trials as Topic; Simvastatin; Uric Acid
PubMed: 27260336
DOI: 10.1007/s40265-016-0591-2 -
Pharmacoepidemiology and Drug Safety Feb 2007Our objective was to determine the association of clinically relevant adverse events from a systematic review and meta-analysis of statin randomized controlled trials... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Our objective was to determine the association of clinically relevant adverse events from a systematic review and meta-analysis of statin randomized controlled trials (RCT).
METHODS
We performed the meta-analysis in the manner of a Cochrane Collaboration systematic review. Outcomes were discontinuances of therapy or muscle-related symptoms due to adverse events. We searched for articles from 1982 through June 2006 in MEDLINE and other databases. The main inclusion criteria were double blind, placebo controlled RCTs with a monotherapy intervention of any marketed statin and active surveillance of adverse events. We excluded studies of drug interactions, organ transplants, or exercise, or those not meeting all of the study quality criteria. The primary analysis was a statin formulation stratified fixed-effect model using Peto odds-ratios (POR). Secondary analyses explored the stability of the primary results.
RESULTS
Over 86,000 study participants from 119 studies were included. Available statins were associated with a lower POR of discontinuance (overall: 0.88 [0.84, 0.93], largest effect with pravastatin: 0.79 [0.74, 0.84]), an elevated POR of rhabdomyolysis (1.59 [0.54, 4.70]) and myositis (2.56 [1.12, 5.85]), and null odds of myalgia (1.09 [0.97, 1.23]). Cerivastatin by comparison demonstrated larger PORs for discontinuances and muscle-related adverse events. Secondary analyses demonstrated the stability of the results.
CONCLUSIONS
Overall, discontinuation of statin therapy due to adverse events was no worse than placebo. The risks of muscle-related adverse events were in general agreement with the known risks of statins.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Myositis; Odds Ratio; Randomized Controlled Trials as Topic; Research Design; Rhabdomyolysis; Risk Assessment
PubMed: 17072896
DOI: 10.1002/pds.1341 -
BMC Medicine Feb 2013Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates more than other lipid-modulating drugs, although evidence from... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates more than other lipid-modulating drugs, although evidence from randomized controlled trials also suggests that statins unexpectedly increase the risk of diabetes and improve immune function. Physiologically, statins would be expected to lower androgens because statins inhibit production of the substrate for the local synthesis of androgens and statins' pleiotropic effects are somewhat similar to the physiological effects of lowering testosterone, so we hypothesized that statins lower testosterone.
METHODS
A meta-analysis of placebo-controlled randomized trials of statins to test the a priori hypothesis that statins lower testosterone. We searched the PubMed, Medline and ISI Web of Science databases until the end of 2011, using '(Testosterone OR androgen) AND (CS-514 OR statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR rosuvastatin OR pravastatin)' restricted to randomized controlled trials in English, supplemented by a bibliographic search. We included studies with durations of 2+ weeks reporting changes in testosterone. Two reviewers independently searched, selected and assessed study quality. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting.
RESULTS
Of the 29 studies identified 11 were eligible. In 5 homogenous trials of 501 men, mainly middle aged with hypercholesterolemia, statins lowered testosterone by -0.66 nmol/l (95% confidence interval (CI) -0.14 to -1.18). In 6 heterogeneous trials of 368 young women with polycystic ovary syndrome, statins lowered testosterone by -0.40 nmol/l (95% CI -0.05 to -0.75). Overall statins lowered testosterone by -0.44 nmol/l (95% CI -0.75 to -0.13).
CONCLUSIONS
Statins may partially operate by lowering testosterone. Whether this is a detrimental side effect or mode of action warrants investigation given the potential implications for drug development and prevention of non-communicable chronic diseases. See commentary article here http://www.biomedcentral.com/1741-7015/11/58.
Topics: Adult; Aged; Anticholesteremic Agents; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Testosterone
PubMed: 23448151
DOI: 10.1186/1741-7015-11-57