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Acta Neurologica Belgica Aug 2022Amyotrophic lateral sclerosis (ALS) is a paralytic, heterogeneous and progressive disease characterized by the degeneration of both upper and lower motor neurons.... (Meta-Analysis)
Meta-Analysis
Amyotrophic lateral sclerosis (ALS) is a paralytic, heterogeneous and progressive disease characterized by the degeneration of both upper and lower motor neurons. Several studies about the effects of statins drug on the risk of ALS showed contradictory results and evidence for this is inconclusive. So we aimed to perform a meta-analysis on previous studies to clarify the association between statin use and risk of ALS. The databases including PubMed, Scopus, and Web of science were searched in February 2021 for studies that reported the association between statin use and risk of ALS. The eligible studies had to provide a report on the effect of statin and the incidence of ALS while comparing it to the control group. Articles that had low statin exposure time, the absence of a control group and an unknown number of ALS patients were excluded. The rate ratio and 95% confidence interval (CI) were used for association measures in case-control and cohort studies. After full-text and abstract review, data from 8 studies with a total of 547,622 participants and 13,890 cases of ALS were entered in the present meta-analysis. We combined eight studies using a random-effect model and the RR for statin users among groups was 0.98 (95% CI 0.80-1.20) which indicates no association between statin and incidence of ALS. Also high heterogeneity was detected across the studies (Q value = 26.62, P = .00; I = 72.71%). In our meta-analysis study, we found no association between statin use and an increase in ALS incidence. This result is in line with some previous studies and provides strong evidence that denies the possible association between statin uptake and disease induction.
Topics: Amyotrophic Lateral Sclerosis; Case-Control Studies; Cohort Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence
PubMed: 34322852
DOI: 10.1007/s13760-021-01753-8 -
JAMA Jul 2023Lipid screening in childhood and adolescence can lead to early dyslipidemia diagnosis. The long-term benefits of lipid screening and subsequent treatment in this... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Lipid screening in childhood and adolescence can lead to early dyslipidemia diagnosis. The long-term benefits of lipid screening and subsequent treatment in this population are uncertain.
OBJECTIVE
To review benefits and harms of screening and treatment of pediatric dyslipidemia due to familial hypercholesterolemia (FH) and multifactorial dyslipidemia.
DATA SOURCES
MEDLINE and the Cochrane Central Register of Controlled Trials through May 16, 2022; literature surveillance through March 24, 2023.
STUDY SELECTION
English-language randomized clinical trials (RCTs) of lipid screening; recent, large US cohort studies reporting diagnostic yield or screen positivity; and RCTs of lipid-lowering interventions.
DATA EXTRACTION AND SYNTHESIS
Single extraction, verified by a second reviewer. Quantitative synthesis using random-effects meta-analysis.
MAIN OUTCOMES AND MEASURES
Health outcomes, diagnostic yield, intermediate outcomes, behavioral outcomes, and harms.
RESULTS
Forty-three studies were included (n = 491 516). No RCTs directly addressed screening effectiveness and harms. Three US studies (n = 395 465) reported prevalence of phenotypically defined FH of 0.2% to 0.4% (1:250 to 1:500). Five studies (n = 142 257) reported multifactorial dyslipidemia prevalence; the prevalence of elevated total cholesterol level (≥200 mg/dL) was 7.1% to 9.4% and of any lipid abnormality was 19.2%. Ten RCTs in children and adolescents with FH (n = 1230) demonstrated that statins were associated with an 81- to 82-mg/dL greater mean reduction in levels of total cholesterol and LDL-C compared with placebo at up to 2 years. Nonstatin-drug trials showed statistically significant lowering of lipid levels in FH populations, but few studies were available for any single drug. Observational studies suggest that statin treatment for FH starting in childhood or adolescence reduces long-term cardiovascular disease risk. Two multifactorial dyslipidemia behavioral counseling trials (n = 934) demonstrated 3- to 6-mg/dL greater reductions in total cholesterol levels compared with the control group, but findings did not persist at longest follow-up. Harms reported in the short-term drug trials were similar in the intervention and control groups.
CONCLUSIONS AND RELEVANCE
No direct evidence on the benefits or harms of pediatric lipid screening was identified. While multifactorial dyslipidemia is common, no evidence was found that treatment is effective for this condition. In contrast, FH is relatively rare; evidence shows that statins reduce lipid levels in children with FH, and observational studies suggest that such treatment has long-term benefit for this condition.
Topics: Adolescent; Child; Humans; Cholesterol; Dyslipidemias; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Mass Screening; Hypercholesterolemia
PubMed: 37462700
DOI: 10.1001/jama.2023.8867 -
Therapeutic Drug Monitoring Oct 2021The utility of measuring thiopurine metabolites (TM) to individualize therapy in autoimmune hepatitis (AIH) has not been defined, and the evidence regarding its use in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The utility of measuring thiopurine metabolites (TM) to individualize therapy in autoimmune hepatitis (AIH) has not been defined, and the evidence regarding its use in clinical practice is heterogeneous. This systematic review and meta-analysis aimed to compare the mean concentration of TM between patients in biochemical remission and those not in remission.
METHODS
A systematic literature search was conducted using PubMed, Scopus, the Cochrane Library, and Google Scholar for keywords related to TM and AIH. Two reviewers independently searched and selected studies comparing the levels of 6-methyl mercaptopurine (6-MMP) and 6-thioguanine nucleotide (6-TGN) and their ratio in cases of AIH in remission and otherwise. Meta-analysis was performed by calculating the weighted mean difference using the inverse variance heterogeneity model.
RESULTS
A total of 1066 records were identified through systematic search; of which, 7 (n = 3 pediatric, n = 4 adults) were considered for inclusion, and 442 TM measurements (n = 128 in children) were analyzed. Mean 6-TGN levels were significantly higher among patients in remission than in those who were not, with a pooled weighted mean difference (WMD) of 15.67 [95% confidence interval (CI), 6.68-24.66] pmol/8 × 108 red blood cells (RBC). The difference was higher in the pediatric age group (WMD, 56.11; 95% CI, 13.60-98.62) than in adults (WMD, 13.77; 95% CI, 4.58-22.97). There was no significant difference in the 6-MMP levels (WMD, -431.7; 95% CI, -1237.4 to 373.9 pmol/8 × 108 RBC; I2 = 82%; n = 3 studies) or 6-MMP/6-TGN ratio among the patients who were in biochemical remission and those who were not (WMD, -0.97; 95% CI, -5.77 to 3.84; I2 = 82%; n = 3 studies).
CONCLUSIONS
This meta-analysis suggests a link between 6-TGN levels and biochemical remission in AIH. Further high-quality studies are required to determine the therapeutic cutoff of 6-TGN.
Topics: Adult; Azathioprine; Child; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Mercaptopurine; Thioguanine
PubMed: 33346628
DOI: 10.1097/FTD.0000000000000848 -
Endocrine Aug 2023This systematic review aimed to evaluate the benefits and harms of fibrate therapy, alone or in combination with statins, in adult patients with type 2 diabetes (T2D). (Meta-Analysis)
Meta-Analysis
PURPOSE
This systematic review aimed to evaluate the benefits and harms of fibrate therapy, alone or in combination with statins, in adult patients with type 2 diabetes (T2D).
METHODS
A comprehensive search was conducted in six databases, from inception to January 27, 2022. Clinical trials that compared fibrate therapy with other lipid-lowering interventions or placebo were included. Outcomes of interest comprised cardiovascular (CV) events, complications of T2D, metabolic profile, and adverse events. Random-effects meta-analyses were performed to estimate mean differences (MD) and risk ratios (RR), alongside 95% confidence intervals (CI).
RESULTS
A total of 25 studies were included, six comparing fibrates against statins, 11 against placebo, and eight evaluating the combination of fibrates with statins. Overall risk of bias was rated as moderate, and most outcomes rendered low confidence per GRADE approach. Fibrates showed reduction of serum triglycerides (TGs) (MD -17.81, CI -33.92 to -1.69) and a marginal increase of high-density lipoprotein cholesterol (HDL-c) (MD: 1.60, CI 0.29 to 2.90) in adults with T2D, but no differences were found in CV events when compared to statin therapy (RR 0.99, CI 0.76 to 1.09). When used in combination with statins, no major differences were exhibited regarding lipid profile and CV outcomes. Adverse events were comparable between fibrate and statin monotherapies (e.g., RR of 1.03 for rhabdomyolysis, and 0.90 for gastrointestinal events).
CONCLUSIONS
Fibrate therapy in patients with T2D results in a marginal improvement of TGs and HDL-c but without reducing the risk of CV events and mortality. Their use should be reserved for very specific scenarios after a deliberative dialogue between patients and clinicians regarding their benefits and harms.
Topics: Adult; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Fibric Acids; Diabetes Mellitus, Type 2; Cholesterol, HDL; Triglycerides; Cardiovascular Diseases
PubMed: 37247046
DOI: 10.1007/s12020-023-03401-y -
Phytomedicine : International Journal... Apr 2023Berberine has been widely used for the adjuvant therapy of several cardiovascular diseases (CVDs). However, evidence for its efficacy remains controversial. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Berberine has been widely used for the adjuvant therapy of several cardiovascular diseases (CVDs). However, evidence for its efficacy remains controversial.
PURPOSE
This study aimed to evaluate the efficacy and safety of berberine in CVDs.
STUDY DESIGN
A systematic review and meta-analysis of randomized controlled trials (RCTs).
METHODS
We searched ten electronic databases for articles from inception to December 23, 2022. RCTs comparing berberine alone or combined with statins versus statins or routine for CVDs were included. Meta-analysis was performed according to the Cochrane Handbook.
RESULTS
Forty-four RCTs were included with 4606 patients. There were no differences between berberine alone and routine or statins in improving total cholesterol (TC) (SMD, 0.43; 95% CI, -0.39 to 1.24; p = 0.30; I = 95%), triglyceride (TG) (SMD, -0.14; 95% CI, -0.49 to 0.21; p = 0.44; I = 76%), low-density lipoprotein cholesterol (LDL-C) (SMD, 0.69; 95% CI, -0.23 to 1.60; p = 0.14; I = 96%), high-density lipoprotein cholesterol (HDL-C) (SMD, 0.55; 95% CI, -0.48 to 1.57; p = 0.30; I = 96%), and Crouse score levels. Berberine alone significantly reduced National Institute of Health Stroke Scale (NIHSS) score, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intima-media thickness (IMT) levels than routine therapy. Berberine plus statins significantly reduced TC, TG, LDL-C, NIHSS score, hs-CRP, TNF-α, IMT, Crouse score, and number of unstable plaques levels than routine or statins. However, no differences were found between groups in improving HDL-C and IL-6 levels. There were no significant differences between groups in the incidence of adverse reactions.
CONCLUSION
This study suggests that berberine may be a promising alternative for CVDs with no serious adverse reactions. However, our results may be limited by the quality of existing research. High-quality RCTs are needed to provide more convinced evidence.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Berberine; Cardiovascular Diseases; Cholesterol, LDL; C-Reactive Protein; Tumor Necrosis Factor-alpha; Interleukin-6; Randomized Controlled Trials as Topic; Triglycerides; Cholesterol, HDL
PubMed: 36805484
DOI: 10.1016/j.phymed.2023.154716 -
Journal of Gastrointestinal and Liver... Dec 2020The use of statins has been shown to be associated with a decreased risk of cholangiocarcinoma (CCA) in many studies although the results have been inconsistent. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
The use of statins has been shown to be associated with a decreased risk of cholangiocarcinoma (CCA) in many studies although the results have been inconsistent. We conducted this systematic review and meta-analysis to further investigate this possible association by identifying all relevant studies and combining their results together.
METHODS
A comprehensive literature review was conducted utilizing the MEDLINE and EMBASE databases through March 2020 to identify all studies that compared the risk of CCA among individuals who use statins with individuals who do not use statins. Effect estimates from each study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird.
RESULTS
A total of seven studies with 6,251,187 participants fulfilled the eligibility criteria and were included in this meta-analysis. The pooled analysis found a significantly decreased risk of CCA among individuals who use statins compared with individuals who do not use statins with the pooled odds ratio of 0.68 (95% CI: 0.52-0.89; I 2 96%).
CONCLUSIONS
The current systematic review and meta-analysis found a significant association between the use of statins and a decreased risk of CCA.
Topics: Bile Duct Neoplasms; Cholangiocarcinoma; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 33331334
DOI: 10.15403/jgld-2990 -
The Cochrane Database of Systematic... Jun 2020Pitavastatin is the newest statin on the market, and the dose-related magnitude of effect of pitavastatin on blood lipids is not known. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pitavastatin is the newest statin on the market, and the dose-related magnitude of effect of pitavastatin on blood lipids is not known.
OBJECTIVES
Primary objective To quantify the effects of various doses of pitavastatin on the surrogate markers: LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides in participants with and without cardiovascular disease. To compare the effect of pitavastatin on surrogate markers with other statins. Secondary objectives To quantify the effect of various doses of pitavastatin on withdrawals due to adverse effects. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for trials up to March 2019: the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2019), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.
SELECTION CRITERIA
RCT and controlled before-and-after studies evaluating the dose response of different fixed doses of pitavastatin 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 studies to be included, and extracted data. We entered data from RCT and controlled before-and-after studies into Review Manager 5 as continuous and generic inverse variance data, respectively. Withdrawals due to adverse effects (WDAE) information was collected from the RCTs. We assessed all included trials using the Cochrane 'Risk of bias' tool under the categories of allocation (selection bias), blinding (performance bias and detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and other potential sources of bias.
MAIN RESULTS
Forty-seven studies (five RCTs and 42 before-and-after studies) evaluated the dose-related efficacy of pitavastatin in 5436 participants. The participants were of any age with and without cardiovascular disease, and pitavastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over doses of 1 mg to 16 mg revealed strong linear dose-related effects on blood total cholesterol and LDL cholesterol and triglycerides. There was no dose-related effect of pitavastatin on blood HDL cholesterol, which was increased by 4% on average by pitavastatin. Pitavastatin 1 mg/day to 16 mg/day reduced LDL cholesterol by 33.3% to 54.7%, total cholesterol by 23.3% to 39.0% and triglycerides by 13.0% to 28.1%. For every two-fold dose increase, there was a 5.35% (95% CI 3.32 to 7.38) decrease in blood LDL cholesterol, a 3.93% (95% CI 2.35 to 5.50) decrease in blood total cholesterol and a 3.76% (95% CI 1.03 to 6.48) decrease in blood triglycerides. The certainty of evidence for these effects was judged to be high. When compared to other statins for its effect to reduce LDL cholesterol, pitavastatin is about 6-fold more potent than atorvastatin, 1.7-fold more potent than rosuvastatin, 77-fold more potent than fluvastatin and 3.3-fold less potent than cerivastatin. For the placebo group, there were no participants who withdrew due to an adverse effect per 109 subjects and for all doses of pitavastatin, there were three participants who withdrew due to an adverse effect per 262 subjects.
AUTHORS' CONCLUSIONS
Pitavastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. Based on the effect on LDL cholesterol, pitavastatin is about 6-fold more potent than atorvastatin, 1.7-fold more potent than rosuvastatin, 77-fold more potent than fluvastatin and 3.3-fold less potent than cerivastatin. There were not enough data to determine risk of withdrawal due to adverse effects due to pitavastatin.
Topics: Atorvastatin; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Controlled Before-After Studies; Drug Administration Schedule; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Pyridines; Quinolines; Randomized Controlled Trials as Topic; Rosuvastatin Calcium; Sex Factors; Triglycerides
PubMed: 32557581
DOI: 10.1002/14651858.CD012735.pub2 -
Nitric Oxide : Biology and Chemistry Mar 2022We conducted an updated systematic review and meta-analysis of the effect of statins on serum or plasma concentrations of the endogenous inhibitor of endothelial nitric... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We conducted an updated systematic review and meta-analysis of the effect of statins on serum or plasma concentrations of the endogenous inhibitor of endothelial nitric oxide synthase, asymmetric N,N-dimethyl-l-arginine (ADMA).
METHODS
A systematic literature search was conducted in the electronic databases PubMed, Web of Science, and Scopus, from inception to July 2021. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist for analytical studies and GRADE, respectively.
RESULTS
In 23 studies, reporting 25 treatment arms in 845 participants (mean age 53 years, 57% males, treatment duration 4-48 weeks), statins significantly reduced ADMA concentrations (SMD = -0.39, 95% CI -0.62 to -0.16, p = 0.001; moderate certainty of evidence). The extreme heterogeneity observed was substantially reduced in study subgroups of specific class and individual statins, regional areas, and analytical methods for ADMA concentrations. There was no publication bias. In sensitivity analysis, the corresponding SMD values were not substantially modified when individual studies were sequentially removed. Significant associations were observed, in meta-regression, between the SMD and publication year (t = -3.25, p = 0.003), but not baseline cholesterol concentrations.
CONCLUSION
Statin treatment significantly lowers ADMA concentrations. This effect is independent of baseline cholesterol. Prospective studies are required to determine whether ADMA-lowering mediates, at least partly, the protective effects of statins against atherosclerotic cardiovascular disease. (PROSPERO registration number: CRD42021275123).
Topics: Arginine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 35032642
DOI: 10.1016/j.niox.2022.01.001 -
Current Oncology (Toronto, Ont.) Jul 2023Statins are widely used due to their ability to lower plasma cholesterol and offer protection from the effects of atherosclerosis. However, their role in urology and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Statins are widely used due to their ability to lower plasma cholesterol and offer protection from the effects of atherosclerosis. However, their role in urology and specifically bladder cancer remains unclear. We aimed to systematically address this issue in the literature and determine any possible effects of statin therapy on bladder cancer.
METHODS
We searched MEDLINE (PubMed) and Cochrane Library databases for records up to 26 March 2023, for studies evaluating the effects of statins on urinary bladder cancer (UBC). We included all randomized controlled trials (RCTs), cohorts, and case-control studies that were conducted on the adult population. PROSPERO registration number: CRD42023407795.
RESULTS
Database searches returned 2251 reports, and after thorough investigation and assessment for eligibility, 32 reports were included in the analysis. Of them, 4 were RCTs, 6 were case-control studies, and 22 were cohort studies. Our qualitative analysis demonstrated no association between statin administration and UBC local control, recurrence, survival, or mortality, or between statin administration and bacille Calmette-Guérin (BCG) immunotherapy effectiveness. A meta-analysis of 10 trials revealed a non-significant reduction of 11% in UBC risk among users compared with non-users in RCTs (RR: 0.89, 95% CI 0.68-1.16, = 0.37) and a non-significant increase of 32% of UBC risk among statin users compared with non-users in the analysis of the cohort studies (RR: 1.32, 95% CI 0.76-2.30, = 0.33).
CONCLUSIONS
Our results provide strong evidence to support the neutral effect of statins on UBC local control, recurrence, survival, and mortality, and on BCG immunotherapy. Our meta-analysis revealed a non-significant effect on UBC risk among statin users when compared with non-users, indicating no statin effect on UBC incidence and overall prognosis.
Topics: Adult; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; BCG Vaccine; Incidence; Prognosis; Urinary Bladder Neoplasms
PubMed: 37504348
DOI: 10.3390/curroncol30070488 -
International Journal of Environmental... Dec 2022In the United States, a significant amount of the population is affected by hyperlipidemia, which is associated with increased levels of serum low-density lipoprotein... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
In the United States, a significant amount of the population is affected by hyperlipidemia, which is associated with increased levels of serum low-density lipoprotein (LDL-C) and risk of cardiovascular disease. As of 2019, the guidelines set by the American College of Cardiology/American Heart Association advocate for the use of statins as the major contributor to lowering serum LDL-C. While proven to be effective, side effects, including muscle-related symptoms and new-onset diabetes mellitus, can make patients unable to tolerate statin therapy. Additionally, there is a subset of the population which does not approach a recommended LDL-C goal on statin treatment. Due to these findings, it was deemed necessary to review the literature of current statin-alternative lipid-lowering therapies.
METHODS
A systematic review of preclinical and clinical papers, and a current meta-analysis, was performed using PubMed and Google Scholar. Following the literature review, a meta-analysis was conducted using ProMeta 3.
RESULTS
Through systematic review and meta-analysis of the current literature, it is suggested that newer lipid-lowering therapies such as proprotein convertase subtilsin-kixen type 9 (PCSK9) inhibitors are a safe and effective statin alternative for the population with statin intolerance. PCSK9 inhibitors were shown to have no significant effect in causing myalgia in patients and showed no increase in adverse cardiovascular outcomes compared to a control of a current antilipemic medication regimen.
DISCUSSION
There are many statin-alternative therapies that should be investigated further as a potential replacement for patients with statin intolerance or as an addition for patients with statin resistance.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Proprotein Convertase 9; PCSK9 Inhibitors; Cholesterol, LDL; Cardiovascular Diseases; Anticholesteremic Agents
PubMed: 36554779
DOI: 10.3390/ijerph192416899