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Endocrine Jan 2024Thyroid eye disease (TED) is the foremost extrathyroidal manifestation of Graves' disease (GD). Currently, available treatments do not entirely prevent the long-term... (Review)
Review
PURPOSE
Thyroid eye disease (TED) is the foremost extrathyroidal manifestation of Graves' disease (GD). Currently, available treatments do not entirely prevent the long-term consequences of TED and have distinct disadvantages. Therefore, this systematic review explored available evidence regarding the efficacy of statins in preventing and treating TED.
METHODS
Relevant studies investigating statin usage in patients with GD or TED were identified by searching Medline (Pubmed and Ovid), Scopus, Web of Science, ProQuest, and Cochrane Library databases (from the database inception to September 2023). The review was done according to the PRISMA statement. Web searching was done independently by two investigators. Two researchers independently extracted the data, and any disagreement was adjudicated by consensus. Based on the study design, the studies' quality appraisal was done using the Newcastle-Ottawa Scale (NOS) and Version 2 of the Cochrane risk-of-bias tool (RoB2).
RESULTS
The literature search identified 145 publications, of which four met the inclusion criteria (Three retrospective cohort studies and one randomized clinical trial) and were reviewed in full text. The two retrospective cohort studies demonstrated the beneficial effects of statins on TED in newly diagnosed GD Stein et al. showed that statins, regardless of the type, prevent or delay TED (HR: 0.74 (0.65-0.84)), especially in men or treatment duration of more than one year. Nilsson et al. fascinatingly revealed that at least 60 days of statin usage in the preceding year could decrease the risk of TED development by around 40%. One RCT showed a higher treatment response for active moderate-to-severe TED in patients with hypercholesterolemia who took atorvastatin 20 mg in addition to ivGC for 24 weeks without any increase in serious side effects. The retrospective study revealed that the need for reconstructive surgery was reduced in patients with severe TED who received statin therapy.
CONCLUSION
Statin therapy could be a potential adjunctive modality for preventing and treating TED.
TRIAL REGISTRATION
PROSPERO registration number: CRD42022315522.
PubMed: 38194219
DOI: 10.1007/s12020-023-03680-5 -
World Neurosurgery: X Jul 2023Despite recent encouraging pharmaceutical and technical breakthroughs in neurosurgical critical care, traumatic brain injury (TBI)-related mortality and morbidity remain... (Review)
Review
Despite recent encouraging pharmaceutical and technical breakthroughs in neurosurgical critical care, traumatic brain injury (TBI)-related mortality and morbidity remain substantial clinical issues. Medication of statins was revealed to enhance outcomes following TBI in animal research. In addition to their main role of decreasing serum cholesterol, statins decrease inflammation and enhance cerebral blood flow. However, research on the efficacy of statins in TBI is still limited. This systematic review was conducted to determine the efficacy of statins in enhancing the clinical outcomes of TBI individuals, and specifically investigate the optimal dose and form of statins. The databases of PubMed, DOAJ, EBSCO, and Cochrane were extensively researched. The date of publication within the last fifteen years was the inclusion criterion. Meta-analyses, clinical trials, and randomized controlled trials were prioritized forms of research publications. Ambiguous remarks, irrelevant correlations to the main issue, or a focus on disorders other than TBI were the exclusion criteria. Thirteen research were included in this study. Simvastatin, atorvastatin, and rosuvastatin were the main form of statins discussed in this study. Enhancement of the Glasgow Coma Scale, survival rates, hospital length of stay, and cognitive outcomes were revealed in this study. This study suggests either simvastatin 40 mg, atorvastatin 20 mg, or rosuvastatin 20 mg for 10 days as the optimal therapeutic forms and doses to be applied in the management of TBI. Pre-TBI statin use was linked to lower risk of mortality in TBI individuals compared to nonusers, whereas statin discontinuation was linked to an increase in mortality.
PubMed: 37251243
DOI: 10.1016/j.wnsx.2023.100211 -
Frontiers in Cardiovascular Medicine 2022The objective of this study was to measure the efficacy of various types and dosages of statins on C-reactive protein (CRP) levels in patients with dyslipidemia or...
The effect of various types and doses of statins on C-reactive protein levels in patients with dyslipidemia or coronary heart disease: A systematic review and network meta-analysis.
OBJECTIVE
The objective of this study was to measure the efficacy of various types and dosages of statins on C-reactive protein (CRP) levels in patients with dyslipidemia or coronary heart disease.
METHODS
Randomized controlled trials were searched from PubMed, Embase, Cochrane Library, OpenGray, and ClinicalTrials.gov. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for data extraction and synthesis. The pairwise meta-analysis compared statins and controls using a random-effects model, and a network meta-analysis compared the types and dosages of statins using the Bayesian random-effects model. The PROSPERO registration number is CRD42021242067.
RESULTS
The study included 37 randomized controlled trials with 17,410 participants and 20 interventions. According to the pairwise meta-analysis, statins significantly decreased CRP levels compared to controls (weighted mean difference [WMD] = -0.97, 95% confidence interval [CI] [-1.31, -0.64], < 0.0001). In the network meta-analysis, simvastatin 40 mg/day appeared to be the best strategy for lowering CRP (Rank = 0.18, WMD = -4.07, 95% CI = [-6.52, -1.77]). The same was true for the high-sensitivity CRP, non-acute coronary syndrome (ACS), <12 months duration, and clear measurement subgroups. In the CRP subgroup (rank = 0.79, WMD = -1.23, 95% CI = [-2.48, -0.08]) and ≥12-month duration subgroup (Rank = 0.40, WMD = -2.13, 95% CI = [-4.24, -0.13]), atorvastatin 80 mg/day was most likely to be the best. There were no significant differences in the dyslipidemia and ACS subgroups ( > 0.05). Node-splitting analysis showed no significant inconsistency ( > 0.05), except for the coronary heart disease subgroup.
CONCLUSION
Statins reduced serum CRP levels in patients with dyslipidemia or coronary heart disease. Simvastatin 40 mg/day might be the most effective therapy, and atorvastatin 80 mg/day showed the best long-term effect. This study provides a reference for choosing statin therapy based on LDL-C and CRP levels.
PubMed: 35966518
DOI: 10.3389/fcvm.2022.936817 -
Journal of the National Cancer Institute Nov 2006Large randomized, controlled clinical trials of lovastatin and gemfibrozil for heart disease prevention have reported statistically significantly lower melanoma... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Large randomized, controlled clinical trials of lovastatin and gemfibrozil for heart disease prevention have reported statistically significantly lower melanoma incidences in persons receiving these medications. Results of in vitro animal model and human case-control studies also suggest that statins and fibrates may reduce the risk of melanoma.
METHODS
We performed a systematic review of trials that randomly assigned participants to receive statins or fibrates versus an alternative therapy for a minimum of 6 months. Trials were identified by searching five electronic databases and the reference lists of eligible publications. Unpublished data were solicited from trial investigators and pharmaceutical companies. A meta-analysis was performed using a fixed-effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate pooled treatment effects. All statistical tests were two-sided.
RESULTS
We obtained data on incident melanomas from 20 of 36 qualifying randomized controlled trials (12 statin trials and eight fibrate trials), with a total of 70,820 participants. A total of 127 melanomas occurred among the 39,426 participants in the statin trials (59 among the 19,872 statin group participants and 68 among the 19,554 control group participants). A total of 27 melanomas occurred among the 31,394 participants enrolled in the fibrate trials (seven among the 12,324 fibrate group participants and 20 among the 19,070 control group participants). Overall, incidence of melanoma was not statistically significantly associated with the use of either statins (OR = 0.87, 95% CI = 0.61 to 1.23) or fibrates (OR = 0.45, 95% CI = 0.20 to 1.01). In a subgroup analysis by drug, only lovastatin use (in one trial) was statistically significantly associated with lower incidence of melanoma (OR = 0.52, 95% CI = 0.27 to 0.99).
CONCLUSIONS
These findings do not validate the possibility that statins or fibrates prevent melanoma.
Topics: Atorvastatin; Bezafibrate; Clofibrate; Gemfibrozil; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Incidence; Lovastatin; Melanoma; Odds Ratio; Pravastatin; Pyrroles; Randomized Controlled Trials as Topic; Reproducibility of Results; Simvastatin; Skin Neoplasms; United States
PubMed: 17077356
DOI: 10.1093/jnci/djj412 -
Health Technology Assessment... Feb 2014Annual screening for adults with type 2 diabetes to detect the early onset of kidney disease is widely recommended, but the recommendations are based on a limited... (Review)
Review
Optimal strategies for identifying kidney disease in diabetes: properties of screening tests, progression of renal dysfunction and impact of treatment - systematic review and modelling of progression and cost-effectiveness.
BACKGROUND
Annual screening for adults with type 2 diabetes to detect the early onset of kidney disease is widely recommended, but the recommendations are based on a limited methodological approach. In addition, there are continuing uncertainties about underlying rates of progression of the condition and the benefits of treatments with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.
OBJECTIVES
We aimed to estimate the clinical value and cost-effectiveness of different screening intervals to diagnose early diabetic kidney disease.
DATA SOURCES
We used the following databases for the literature review (searched January 2005 to August 2010): MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews. Individual patient data were obtained from the Oxford Regional Prospective Diabetes Study and the Collaborative Atorvastatin Diabetes Study.
METHODS
Data from systematically identified randomised trials reporting the impact on renal outcomes of angiotensin-converting enzyme inhibitors and angiotensin 2 receptor blockers for type 1 and type 2 diabetes patients with normoalbuminuria and microalbuminuria were pooled to derive estimates of effect. Individual patient data for type 1 and type 2 diabetes patients were used to obtain parameters describing progression and variability of measurement over time for the albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate. Based on accepted diagnostic thresholds, we modelled whether these tests accurately identified patients who were developing early diabetic kidney disease and required intensification of treatment. Cost-effectiveness analyses were carried out using simulation outcome models to estimate the incremental costs per quality-adjusted life-year (QALY) for different screening intervals.
RESULTS
In total, 49 trials (n = 34,082 patients) were eligible for inclusion in the systematic review. For type 1 diabetes, pooled estimates of urinary albumin excretion (UAE) for treated patients with microalbuminuria were on average 67% [95% confidence interval (CI) 54% to 77%] lower at the end of the trial than for untreated patients. There was no significant treatment effect for patients with normoalbuminuria (p interaction = 0.006). For treated patients with type 2 diabetes and normoalbuminuria or microalbuminuria, UAE was lower by, on average, 21% (95% CI 97% to 32%) or 27% (95% CI 15% to 38%), respectively. The proportion (95% CI) of men and women with type 1 diabetes screened annually for microalbuminuria over 6 years and inaccurately identified as having microalbuminuria would be 48% (43% to 53%) and 55% (48% to 61%), respectively. The corresponding proportions for type 2 diabetes are 36% (32% to 42%) and 48% (41% to 55%). Decreasing the screening interval to 3-yearly would reduce this for men with type 1 diabetes to 38% (33% to 44%), with an increase in those not identified over 6 years from 1.5% (95% CI 1% to 2%) to 4% (95% CI 3% to 5%). For type 1 diabetes, incremental cost per QALY [standard deviation (SD)] of a 5-yearly compared with a 4-yearly screening interval was £3612 (£6586), increasing to £9601 (£34,112) for annual compared with 2-yearly screening. The probability that the intervention is cost saving is around 25%, and it has around an 80% chance of being below a cost-effectiveness threshold of £30,000. For type 2 diabetes, incremental cost per QALY (SD) of a yearly compared with a 2-yearly screening interval was £606 (£1782). The intervention is almost certainly below a cost-effectiveness threshold of £5000.
CONCLUSIONS
These results support current UK guidance, which recommends annual screening with ACR to identify early kidney disease in patients with diabetes, despite a high false-positive rate leading to, at worst, unnecessary or, at best, early therapeutic intervention. For type 1 diabetes, screening costs for annual compared with 2-yearly screening are well within the bounds of accepted cost-effectiveness. Annual screening is even more cost-effective in type 2 diabetes than in type 1 diabetes. Identification of alternative markers for developing diabetic nephropathy may improve targeting of treatment for those at high risk.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diagnostic Tests, Routine; Disease Progression; Female; Humans; Kidney Function Tests; Male; Outcome Assessment, Health Care; Risk Factors
PubMed: 24576414
DOI: 10.3310/hta18140 -
Frontiers in Clinical Diabetes and... 2022Hyperglycemia is associated with a higher cardiovascular risk, as evidenced by increased carotid-intima media thickness (CIMT) in youth with diabetes. We conducted a...
INTRODUCTION
Hyperglycemia is associated with a higher cardiovascular risk, as evidenced by increased carotid-intima media thickness (CIMT) in youth with diabetes. We conducted a systematic review and meta-analysis to assess the effect of pharmacological or non-pharmacological interventions on CIMT in children and adolescents with prediabetes or diabetes.
METHODS
We conducted systematic searches of MEDLINE, EMBASE, and CENTRAL, together with supplementary searches in trial registers and other sources for studies completed up to September 2019. Interventional studies assessing ultrasound CIMT in children and adolescents with prediabetes or diabetes were considered for inclusion. Where appropriate, data were pooled across studies using random-effect meta-analysis. Quality was assessed using The Cochrane Collaboration's risk-of-bias tool and a CIMT reliability tool.
RESULTS
Six studies involving 644 children with type 1 diabetes mellitus were included. No study involved children with prediabetes or type 2 diabetes. Three randomized controlled trials (RCTs) evaluated the effects of metformin, quinapril, and atorvastatin. Three non-randomized studies, with a before-and-after design, evaluated the effects of physical exercise and continuous subcutaneous insulin infusion (CSII). The mean CIMT at baseline ranged from 0.40 to 0.51 mm. The pooled difference in CIMT was -0.01 mm (95% CI: -0.04 to 0.01) for metformin compared to placebo (2 studies; 135 participants; I: 0%). The difference in CIMT was -0.01 mm (95% CI: -0.03 to 0.01) for quinapril compared to placebo (1 study; 406 participants). The mean change from baseline in CIMT was -0.03 mm (95% CI: -0.14 to 0.08) after physical exercise (1 study; 7 participants). Inconsistent results were reported for CSII or for atorvastatin. CIMT measurement was rated at a higher quality on all reliability domains in 3 (50%) studies. The confidence in results is limited by the low number of RCTs and their small sample sizes, as well as the high risk of bias in before-and-after studies.
CONCLUSIONS
Some pharmacological interventions may decrease CIMT in children with type 1 diabetes. However, there is great uncertainty with respect to their effects and no strong conclusions can be drawn. Further evidence from larger RCTs is required.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42017075169.
PubMed: 36992735
DOI: 10.3389/fcdhc.2022.882504 -
European Review For Medical and... Sep 2021The aim of this systematic review is to assess the efficacy of locally delivered statins used in adjunct to scaling and root planing (SRP), compared with SRP alone. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this systematic review is to assess the efficacy of locally delivered statins used in adjunct to scaling and root planing (SRP), compared with SRP alone.
MATERIALS AND METHODS
An electronic and hand search was carried out up to April 2020. Only randomized controlled trials (RCTs) were included. Clinical attachment level gain (CALgain) and probing depth reduction (PDred), modified sulcular bleeding index reduction (mSBIred), and intrabony defect reduction (IBDred) were the investigated outcomes. Meta-analysis was performed, and the power of the meta-analytic findings was determined by trial sequential analysis (TSA). Studies were also sub-grouped based on the type of statin used. Statistical heterogeneity and publication bias were assessed.
RESULTS
Twenty RCTs were included (1212 patients, 1289 defects). An overall statistically significant effect size in favor of statins for CALgain and PDred was found. As opposed to atorvastatin and rosuvastatin, simvastatin did not reach statistical significance for these outcomes, as shown by the sub-group analysis.
CONCLUSIONS
Within the limits of the available studies, the local administration of statins (in particular, atorvastatin and rosuvastatin) in adjunct to SRP may result in additional significant improvement in terms of CALgain and PDred compared with SRP alone. The high heterogeneity of data and the high risk of bias found, however, impose caution. No approved preparations, moreover, exist, and further well-designed RCTs from independent research centers are needed to confirm the beneficial effects of the different statins and their mutual differences in the non-surgical periodontal treatment.
Topics: Chronic Periodontitis; Combined Modality Therapy; Dental Scaling; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic; Root Planing; Treatment Outcome
PubMed: 34604965
DOI: 10.26355/eurrev_202109_26792 -
Journal of Dentistry Dec 2017To evaluate the effect of local and/or systemic statin use as an adjunct to non-surgical and/or surgical periodontal therapy. (Review)
Review
OBJECTIVES
To evaluate the effect of local and/or systemic statin use as an adjunct to non-surgical and/or surgical periodontal therapy.
DATA
Literature search according to PRISMA guidelines with the following eligibility criteria: (a) English or German language; (b) interventional studies; (c) statins as monotherapy or as an adjunct to non-surgical and/or surgical treatment of periodontitis; (d) clinical and/or radiographic treatment effect size of statin intake reported.
SOURCES
Medline (PubMed), Embase (Ovid), CENTRAL (Ovid).
STUDY SELECTION
Thirteen clinical studies regarding local application and 2 with systemic administration of statins as an adjunct to non-surgical treatment (SRP) and 4 studies regarding intrasurgical statin application with a maximum follow-up of 9 months could be included; simvastatin, atorvastatin, and rosuvastatin were used. Local but not systemic statin application as an adjunct to SRP yielded significantly larger probing pocket depth (PD), radiographic defect depth (RDD), and bleeding index reduction, and larger clinical attachment level gain, and less residual PD and RDD (p≤0.016); rosuvastatin appeared as the most efficacious. Three of 4 studies reported a significant positive effect of intrasurgical statin application. No adverse events were reported after statin use. The vast majority of the included studies were from the same research group.
CONCLUSIONS
Significant additional clinical and radiographic improvements are obtained after local, but not systemic, statin use as an adjunct to SRP in deep pockets associated with intrabony defects and seemingly with furcation defects; intrasurgical statin application seems similarly beneficial. Confirmation of these results, and especially of the effect size, from other research groups is warranted.
Topics: Atorvastatin; Databases, Factual; Drug Administration Routes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Meta-Analysis as Topic; Periodontal Attachment Loss; Periodontal Diseases; Periodontal Index; Periodontal Pocket; Periodontitis; Rosuvastatin Calcium; Simvastatin
PubMed: 28855141
DOI: 10.1016/j.jdent.2017.08.011 -
The Cochrane Database of Systematic... Aug 2011Statins have been claimed to be effective in the acute phase of ischemic stroke. The potential positive actions of statins during an acute cerebrovascular ischemic event... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Statins have been claimed to be effective in the acute phase of ischemic stroke. The potential positive actions of statins during an acute cerebrovascular ischemic event are two-fold: a neuroprotective effect, limiting damage and improving recovery; and a preventative effect on early recurrence.
OBJECTIVES
To quantify the potential benefits and harms of statins in the acute treatment of cerebrovascular ischemic events (both transient ischemic attacks (TIAs) and ischemic stroke).
SEARCH STRATEGY
We searched the Cochrane Stroke Group's Trials Register (November 2010); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4); MEDLINE (1950 to November 2010); and EMBASE (1980 to November 2010). In an effort to identify further published, unpublished and ongoing trials we searched ongoing trials and research registers (November 2010), checked reference lists from relevant articles and contacted authors.
SELECTION CRITERIA
We included all randomized controlled trials (RCTs) comparing statins (any type and dosage) versus placebo or no treatment, administered within two weeks of the onset of acute ischemic stroke or TIA.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion and extracted data. We assessed methodological quality and, when necessary, contacted study authors for additional data. We based quantitative analysis of outcome on the intention-to-treat principle. The primary outcomes were mortality from ischemic stroke and mortality from adverse drug effects, bleedings and infections. We estimated the overall treatment effect by the pooled odds ratio (OR) with 95% confidence interval (CI) using a fixed-effect model (Mantel-Haenszel).
MAIN RESULTS
We included eight RCTs involving 625 participants. Only one study was judged as 'low risk' of bias. There were insufficient published data from the eight studies for all planned primary and secondary outcomes. No patients died from ischemic stroke or from adverse drug effects, bleeding or infections among the 444 participants in the six studies where these outcomes were reported. Statin treatment did not reduce all-cause mortality compared with placebo or no treatment (OR 1.51, 95% CI 0.60 to 3.81) in the 431 patients enrolled in seven studies. No cases of rhabdomyolysis (the breakdown of muscle fibres resulting in the release of muscle fibre contents (myoglobin) into the bloodstream) occurred in 274 patients enrolled in three studies.
AUTHORS' CONCLUSIONS
Insufficient data were available from randomized trials to establish if statins are safe and effective in cases of acute ischemic stroke and TIA.
Topics: Atorvastatin; Cause of Death; Clopidogrel; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ischemic Attack, Transient; Neuroprotective Agents; Platelet Aggregation Inhibitors; Pyrroles; Randomized Controlled Trials as Topic; Simvastatin; Stroke; Ticlopidine
PubMed: 21833959
DOI: 10.1002/14651858.CD007551.pub2 -
The Pharmacogenomics Journal Jun 2021This meta-analysis was conducted to determine the genotypic effects of rs4149056 and rs2306283 polymorphism in SLCO1B1 gene on myopathy in patients with statin. Studies... (Meta-Analysis)
Meta-Analysis
This meta-analysis was conducted to determine the genotypic effects of rs4149056 and rs2306283 polymorphism in SLCO1B1 gene on myopathy in patients with statin. Studies were searched using multiple databases and selected following inclusion criteria. Two reviewers independently performed data extraction and assessments for risk of bias. Fixed-or-random-effect was applied to pool allele frequency/effects. Mixed-effect logit model was used to pool genotypic effects using individual patient data. Heterogeneity and publication bias were explored. Fourteen studies were pooled for rs4149056; the minor C allele frequency were 15% in Caucasians and 14% in Asians. Six studies were pooled for rs2306283; the minor G allele frequency was 34% in Caucasian and 75% in Asians. Genotypic effects of rs4149056 polymorphism in Caucasians indicated that statin users who carried CC and TC genotypes had a significantly higher risk of myopathy than those who carried TT genotype, with a pooled odds ratio (OR) of 2.9 (95% confidence interval, 1.59, 5.34) and 1.6 (1.20, 2.16), respectively. For subgroup analysis, CC and TC genotypes also suggested a higher risk of myopathy in simvastatin users [OR = 2.8 (1.17, 6.77) and OR = 1.8 (1.15, 2.77), respectively] and in atorvastatin users [OR = 4.0 (1.23, 12.63) and OR = 2.0 (1.11, 3.52), respectively] than those who carried TT genotype. There was no significant association between rs2306283 polymorphism and myopathy in Caucasians and Asians. There was no evidence of publication bias for both polymorphisms.
Topics: Animals; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver-Specific Organic Anion Transporter 1; Muscular Diseases
PubMed: 33608664
DOI: 10.1038/s41397-021-00208-w