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Pharmacological Research Sep 2016Statin therapy may lower plasma lipid concentrations, but the evidence in HIV-infected patients is still unclear. Therefore, we aimed to investigate the impact of statin... (Meta-Analysis)
Meta-Analysis Review
A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials investigating the effects of statin therapy on plasma lipid concentrations in HIV-infected patients.
Statin therapy may lower plasma lipid concentrations, but the evidence in HIV-infected patients is still unclear. Therefore, we aimed to investigate the impact of statin therapy on plasma lipid concentrations through a systematic review of the literature and meta-analysis of available randomized controlled trials (RCTs). The literature search included PUBMED, SCOPUS, Web of Science and Google Scholar up to October 30, 2015. The meta-analysis was performed using either a fixed-effects or random-effect model according to I(2) statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Two investigators independently reviewed the title or abstract, further reviewed the full-texts and extracted information on study characteristics and study outcomes. Meta-analysis of 12 RCTs with 697 participants suggested significant reductions in plasma concentrations of low density lipoprotein (LDL) cholesterol (WMD: -0.72mmol/L [-27.8mg/dL], 95%CI: -1.04, -0.39, p<0.001; I(2)=85.7%), total cholesterol (WMD: -1.03mmol/L [-39.8mg/dL], 95%CI: -1.42, -0.64, p<0.001; I(2)=94.7%) and non-high density lipoprotein cholesterol (non-HDL-C) (WMD: -0.81mmol/L [-31.3mg/dl], 95%CI: -1.32, -0.30, p=0.002; I(2)=76.5%), and elevations in HDL-C (WMD: 0.072mmol/L [2.8mg/dL], 95%CI: 0.053, 0.092, p<0.001; I(2)=0%) following treatment with statins (mostly of moderate-intensity). No significant alteration in plasma triglycerides (TG) concentrations was found (WMD: -0.16mmol/L [-14.2mg/dL], 95%CI: -0.61, 0.29, p=0.475; I(2)=90.2%). All these effects were robust in sensitivity analysis, suggesting that the computed effect is not driven by any single study. In subgroup analysis, no significant difference was found among different statins in terms of changing plasma concentrations of LDL-C, HDL-C and TG. However, atorvastatin was found to be more efficacious in reducing plasma total cholesterol concentrations (p<0.001). In conclusion, the meta-analysis suggested significant reductions in plasma concentrations of LDL-C, total cholesterol and non-HDL-C, and elevations in HDL-C, but no significant alteration in plasma TG following treatment with statins.
Topics: Adult; Anti-HIV Agents; Biomarkers; Dyslipidemias; Female; HIV Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome
PubMed: 27350264
DOI: 10.1016/j.phrs.2016.06.005 -
World Neurosurgery May 2024Chronic subdural hematoma (CSDH) is a common neurological condition, especially in the elderly population. Atorvastatin has shown the potential to reduce the recurrence... (Review)
Review
BACKGROUND
Chronic subdural hematoma (CSDH) is a common neurological condition, especially in the elderly population. Atorvastatin has shown the potential to reduce the recurrence of CSDH and improve overall outcomes. New studies have emerged since the last meta-analysis, increasing the sample size and the variety of outcomes analyzed.
METHODS
We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for studies comparing the use of atorvastatin in CSDH patients with a control group or placebo. The primary outcome was the recurrence of CSDH. Secondary outcomes of interest were hematoma volume, composite adverse effects, mortality, and neurological function, measured by the Glasgow Outcome Scale and Barthel index for activities of daily living.
RESULTS
Seven studies, of which 2 were randomized controlled trials, were included, containing 1192 patients. Overall recurrence significantly decreased compared to the control group (risk ratio [RR] 0.46; 95% confidence interval [CI] 0.25-0.83; P=0.009). The benefits of atorvastatin were sustained in the subgroup analysis of patients who underwent initial conservative therapy (RR 0.40; 95% CI 0.22-0.70; P=0.001). However, there was no significant difference when atorvastatin was combined with surgical intervention (RR 0.53; 95% CI 0.21-1.32; P=0.17). Adverse effects were not increased by atorvastatin (RR 0.82; 95% CI 0.51-1.34; P=0.44).
CONCLUSIONS
Atorvastatin might be beneficial in reducing CSDH recurrence, especially in conservative treatment patients. Atorvastatin was not significantly associated with adverse effects. Larger, higher-quality randomized studies are needed to adequately evaluate the efficacy, safety, and optimal dose of atorvastatin in CSDH patients.
PubMed: 38759787
DOI: 10.1016/j.wneu.2024.05.069 -
The Cochrane Database of Systematic... Jan 2020Cerivastatin was the most potent statin until it was withdrawn from the market due to a number of fatalities due to rhabdomyolysis, however, the dose-related magnitude... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cerivastatin was the most potent statin until it was withdrawn from the market due to a number of fatalities due to rhabdomyolysis, however, the dose-related magnitude of effect of cerivastatin on blood lipids is not known.
OBJECTIVES
Primary objective To quantify the effects of various doses of cerivastatin on the surrogate markers: LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides in children and adults with and without cardiovascular disease. The aim of this review is to examine the pharmacology of cerivastatin by characterizing the dose-related effect and variability of the effect of cerivastatin on surrogate markers. Secondary objectives To quantify the effect of various doses of cerivastatin compared to placebo on withdrawals due to adverse effects. To compare the relative potency of cerivastatin with respect to fluvastatin, atorvastatin and rosuvastatin for LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides.
SEARCH METHODS
The Cochrane Hypertension Information Specialist searched the following databases for RCTs up to March 2019: CENTRAL (2019, Issue 3), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov.We also searched the European Patent Office, FDA.gov, and ProQuest Dissertations & Theses, and contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.
SELECTION CRITERIA
RCTs and controlled before-and-after studies evaluating the dose response of different fixed doses of cerivastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without cardiovascular disease.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed eligibility criteria for trials to be included and extracted data. We entered data from RCTs and controlled before-and-after studies into Review Manager 5 as continuous and generic inverse variance data respectively. We collected information on withdrawals due to adverse effects from the RCTs. We assessed all trials using the 'Risk of bias' tool under the categories of sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other potential biases.
MAIN RESULTS
Fifty trials (19 RCTs and 31 before-and-after studies) evaluated the dose-related efficacy of cerivastatin in 12,877 participants who had their LDL cholesterol measured. The participants were of any age with and without cardiovascular disease and the trials studied cerivastatin effects within a treatment period of three to 12 weeks. Cerivastatin 0.025 mg/day to 0.8 mg/day caused LDL cholesterol decreases of 11.0% to 40.8%, total cholesterol decreases of 8.0% to 28.8% and triglyceride decreases of 9.0% to 21.4%. We judged the certainty of evidence for these effects to be high. Log dose-response data over doses of 2.5 mg to 80 mg revealed strong linear dose-related effects on LDL cholesterol, total cholesterol and triglycerides. When compared to fluvastatin, atorvastatin and rosuvastatin, cerivastatin was about 250-fold more potent than fluvastatin, 20-fold more potent than atorvastatin and 5.5-fold more potent than rosuvastatin at reducing LDL cholesterol; 233-fold more potent than fluvastatin, 18-fold more potent than atorvastatin and six-fold more potent than rosuvastatin at reducing total cholesterol; and 125-fold more potent than fluvastatin, 11-fold more potent than atorvastatin and 13-fold more potent than rosuvastatin at reducing triglycerides. There was no dose-related effect of cerivastatin on HDL cholesterol, but overall cerivastatin increased HDL cholesterol by 5%. There was a high risk of bias for the outcome withdrawals due to adverse effects, but a low risk of bias for the lipid measurements. Withdrawals due to adverse effects were not different between cerivastatin and placebo in 11 of 19 of these short-term trials (risk ratio 1.09, 95% confidence interval 0.68 to 1.74).
AUTHORS' CONCLUSIONS
The LDL cholesterol, total cholesterol, and triglyceride lowering effect of cerivastatin was linearly dependent on dose. Cerivastatin log dose-response data were linear over the commonly prescribed dose range. Based on an informal comparison with fluvastatin, atorvastatin and rosuvastatin, cerivastatin was about 250-fold more potent than fluvastatin, 20-fold more potent than atorvastatin and 5.5-fold more potent than rosuvastatin in reducing LDL cholesterol, and 233-fold greater potency than fluvastatin, 18-fold greater potency than atorvastatin and six-fold greater potency than rosuvastatin at reducing total cholesterol. This review did not provide a good estimate of the incidence of harms associated with cerivastatin because of the short duration of the trials and the lack of reporting of adverse effects in 42% of the RCTs.
Topics: Cholesterol, HDL; Cholesterol, LDL; Dose-Response Relationship, Drug; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Lipids; Pyridines; Randomized Controlled Trials as Topic; Treatment Outcome; Triglycerides
PubMed: 31981471
DOI: 10.1002/14651858.CD012501.pub2 -
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 -
Central European Journal of Urology 2021The clinical effect of pharmacotherapy on prostate morphometric parameters is largely unknown. The sole exception is 5α-reductase inhibitors (5-ARI) that reduce...
The effect of pharmacotherapy on prostate volume, prostate perfusion and prostate-specific antigen (prostate morphometric parameters) in patients with lower urinary tract symptoms and benign prostatic obstruction. A systematic review and meta-analysis.
INTRODUCTION
The clinical effect of pharmacotherapy on prostate morphometric parameters is largely unknown. The sole exception is 5α-reductase inhibitors (5-ARI) that reduce prostate volume and prostate-specific antigen (PSA). This review assesses the effect of pharmacotherapy on prostate parameters effect on prostate parameters, namely total prostate volume (TPV), transitional zone volume (TZV), PSA and prostate perfusion.
MATERIAL AND METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) reporting on morphometric parameters' changes after pharmacotherapy, as primary or secondary outcomes. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RCTs' quality was assessed by the Cochrane tool and the criteria of the Agency for Healthcare Research and Quality. The effect magnitude was expressed as standard mean difference (SMD). The study protocol was published on PROSPERO (CRD42020170172).
RESULTS
Sixty-seven RCTs were included in the review and 18 in the meta-analysis. The changes after alpha-blockers are comparable to placebo. Long-term studies reporting significant changes from baseline, result from physiologic growth. Finasteride and dutasteride demonstrated large effect sizes in TPV reduction ([SMD]: -1.15 (95% CI: -1.26 to -1.04, p <0.001, and [SMD]:-0.66 (95% CI: -0.83 to -0.49, p <0.001, respectively), and similar PSA reductions. Dutasteride's effect appears earlier (1 vs 3 month), the changes reach a maximum at month 12 and are sustained thereafter. Phosphodiesterase-5 (PDE-5) inhibitors have no effect on morphometric parameters. Phytotherapy's effect on TPV is non-significant [SMD]: 0.12 (95% CI: -0.03 to 0.27, p = 0.13). Atorvastatin reduces TPV as compared to placebo (-11.7% vs +2.5%, p <0.01). Co-administration of testosterone with dutasteride spares the prostate from the androgenic stimulation as both TPV and PSA are reduced significantly.
CONCLUSIONS
The 5-ARIs show large effect size in reducing TPV and PSA. Tamsulosin improves perfusion but no other effect is evident. PDE-5 inhibitors and phytotherapy do not affect morphometric parameters. Atorvastatin reduces TPV and PSA as opposed to testosterone supplementation.
PubMed: 34729231
DOI: 10.5173/ceju.2021.132.R1 -
Reumatologia 2022Statins are a class of lipid-lowering medications used worldwide by millions of people and are safe for frequent use in most patients. However, they cause necrotizing... (Review)
Review
Statins are a class of lipid-lowering medications used worldwide by millions of people and are safe for frequent use in most patients. However, they cause necrotizing autoimmune myopathy in some patients. We reviewed case reports of 80 patients from 2010 to present diagnosed with statin-induced necrotizing autoimmune myopathy (SINAM), aiming to analyze the clinical, physiological, serologic characteristics and outcomes of SINAM. The mean age of these patients was 66 ±9.4, the majority being male (61.3%). All patients reported proximal muscle weakness, and a few had myalgias, extra muscular symptoms such as dysphagia, and pulmonary complications. Most of the patients were on atorvastatin, simvastatin, or rosuvastatin. The mean creatine kinase was 10,094.2 ±7,351.7 U/l, and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme was positive for 93.8% of patients. The majority of patients were started on steroids; other treatments were also used. Prompt cessation of statins and initiation of immunosuppressants reduced morbidity and mortality.
PubMed: 35645423
DOI: 10.5114/reum.2022.114108 -
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 -
Advanced Pharmaceutical Bulletin Sep 2020Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis are two forms of fatty liver disease with benign and malignant nature, respectively. These two conditions... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis are two forms of fatty liver disease with benign and malignant nature, respectively. These two conditions can cause an increased risk of liver cirrhosis and hepatocellular carcinoma. Given the importance and high prevalence of NAFLD, it is necessary to investigate the results of different studies in related scope to provide a clarity guarantee of effectiveness. Therefore, this systematic review and meta-analysis aim to study the efficacy of various medications used in the treatment of NAFLD. A systematic search of medical databases identified 1963 articles. After exclusion of duplicated articles and those which did not meet our inclusion criteria, eta-analysis was performed on 84 articles. Serum levels of alanine aminotransferase (ALT), aspartate amino transferase (AST) were set as primary outcomes and body mass index (BMI), hepatic steatosis, and NAFLD activity score (NAS) were determined as secondary outcomes. Based on the P-score of the therapeutic effects on the non-alcoholic steatohepatitis (NASH), we observed the highest efficacy for atorvastatin, tryptophan, orlistat, omega-3 and obeticholic acid for reduction of ALT, AST, BMI, steatosis and NAS respectively. This meta-analysis showed that atorvastatin. life-style modification, weight loss, and BMI reduction had a remarkable effect on NAFLD-patients by decreasing aminotransferases.
PubMed: 33072533
DOI: 10.34172/apb.2020.065 -
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 -
The Cochrane Database of Systematic... Dec 2012Atorvastatin is one of the most widely prescribed drugs and the most widely prescribed statin in the world. It is therefore important to know the dose-related magnitude... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Atorvastatin is one of the most widely prescribed drugs and the most widely prescribed statin in the world. It is therefore important to know the dose-related magnitude of effect of atorvastatin on blood lipids.
OBJECTIVES
To quantify the dose-related effects of atorvastatin on blood lipids and withdrawals due to adverse effects (WDAE).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library Issue 4, 2011, MEDLINE (1966 to November 2011), EMBASE (1980 to November 2011), ISI Web of Science (1899 to November 2011) and BIOSIS Previews (1969 to November 2011). No language restrictions were applied.
SELECTION CRITERIA
Randomised controlled and uncontrolled before-and-after trials evaluating the dose response of different fixed doses of atorvastatin on blood lipids over a duration of 3 to 12 weeks.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. WDAE information was collected from the placebo-controlled trials.
MAIN RESULTS
Two hundred fifty-four trials evaluated the dose-related efficacy of atorvastatin in 33,505 participants. Log dose-response data revealed linear dose-related effects on blood total cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides. Combining all the trials using the generic inverse variance fixed-effect model for doses of 10 to 80 mg/day resulted in decreases of 36% to 53% for LDL-cholesterol. There was no significant dose-related effects of atorvastatin on blood high-density lipoprotein (HDL)-cholesterol. WDAE were not statistically different between atorvastatin and placebo for these short-term trials (risk ratio 0.99; 95% confidence interval 0.68 to 1.45).
AUTHORS' CONCLUSIONS
Blood total cholesterol, LDL-cholesterol and triglyceride lowering effect of atorvastatin was dependent on dose. Log dose-response data was linear over the commonly prescribed dose range. Manufacturer-recommended atorvastatin doses of 10 to 80 mg/day resulted in 36% to 53% decreases of LDL-cholesterol. The review did not provide a good estimate of the incidence of harms associated with atorvastatin because of the short duration of the trials and the lack of reporting of adverse effects in 37% of the placebo-controlled trials.
Topics: Atorvastatin; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dose-Response Relationship, Drug; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Lipids; Pyrroles; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 23235655
DOI: 10.1002/14651858.CD008226.pub2