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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 -
Frontiers in Aging Neuroscience 2021Several pharmacological treatments have been used to treat patients with chronic subdural hematoma (CSDH), although little is known about the comparative effectiveness...
Several pharmacological treatments have been used to treat patients with chronic subdural hematoma (CSDH), although little is known about the comparative effectiveness of different classes of medication. We performed a Bayesian network meta-analysis to compare and rank the efficacy and safety of five drug regimens to determine the best treatment for this group of patients. We systematically searched PubMed, Medline, clinicaltrials.gov, the Cochrane database, and Embase to identify relevant randomized clinical trials (RCTs) comparing drug treatments in adult patients with CSDH. A network meta-analysis was conducted using a Bayesian framework. Random- and fixed-effects models were used to pool the network results, and the preferred model was selected by comparing the deviance information criteria (DIC). Efficacy outcomes included recurrence requiring surgery, changes in hematoma volume, and a good recovery. The safety outcomes were treatment-related adverse events and all-cause mortality. In this Bayesian network meta-analysis, available data were obtained from 12 eligible trials, including 2,098 patients and 5 techniques. Compared to placebo, atorvastatin (RR: 0.45, 95% CrI: 0.24-0.81) and dexamethasone (RR: 0.38, 95% CrI: 0.22-0.63) were similarly effective in reducing recurrence requiring surgery by 55% and 62%, respectively. Dexamethasone (RR: 0.46, 95% CrI: 0.23-0.91) was more effective in reducing recurrence requiring surgery than goreisan. Additionally, atorvastatin reduced the hematoma volume to a greater extent than placebo (MD: -7.44, 95% CrI: -9.49 to -5.43) or goreisan (MD: -14.09, 95% CrI: -23.35 to -4.82). Moreover, tranexamic acid (MD: -12.07, 95% CrI: -21.68 to -2.29) reduced the hematoma volume to a greater extent than goreisan. No significant differences were detected between drugs and placebo with regard to a good recovery. In terms of safety, dexamethasone (RR: 1.96, 95% CrI: 1.20-3.28) increased the risk of mortality compared to placebo. These findings suggest that dexamethasone is the best treatment to reduce recurrence and atorvastatin is the best treatment to reduce hematoma volume in patients with CSDH. However, clinicians should pay close attention to the elevated risk of all-cause mortality and potential adverse events caused by dexamethasone. Future well-designed RCTs with more participants are needed to verify these findings. http://osf.io/u9hqp.
PubMed: 34276343
DOI: 10.3389/fnagi.2021.684501 -
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 -
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 -
BMC Cardiovascular Disorders Dec 2015Previous studies reported that Atorvastatin (ATOR) can improve the efficacy of Mesenchymal stem cells (MSCs) transplantation after acute myocardial infarction (AMI).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Previous studies reported that Atorvastatin (ATOR) can improve the efficacy of Mesenchymal stem cells (MSCs) transplantation after acute myocardial infarction (AMI). However, the results of those studies were inconsistent. To clarify the beneficial effects of atorvastatin added to the cell therapy with MSCs in animal model of acute myocardial infarction (AMI), we performed a systematic review and meta-analysis of case-control studies.
METHODS
Searches were performed using the PubMed database, the Excerpta Medica Database (Embase), the Science Citation Index, the China National Knowledge Information database, the Wanfang database, and the Chinese Scientific and Technological Journal Database (VIP database). The search term included "Atorvastatin (or Ator)", "Mesenchymal Stem Cells (or Mesenchymal Stem Cell or MSC or MSCs)" and "Acute Myocardial Infarction (or Myocardial Infarction or AMI or MI)". The endpoints were the left ventricular ejection fraction (LVEF) in animal model with AMI.
RESULTS
In total, 5 studies were included in the meta-analysis. Pooled analysis indicated a significant LVEF difference at 4 weeks follow-up between MSCs + ATOR combine group and MSCs alone group (95 % CI, 9.09-13.62 %; P < 0.01) with heterogeneity (P = 0.28; P >0.05) and inconsistency (I(2): 22 %).
CONCLUSIONS
Atorvastatin can enhance the existing effects of MSCs transplantation, and this combinational therapy is a superior cell/pharmacological therapeutic approach that merits future preclinical and clinical studies.
Topics: Animals; Atorvastatin; Chi-Square Distribution; Combined Modality Therapy; Disease Models, Animal; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mesenchymal Stem Cell Transplantation; Myocardial Infarction; Myocardium; Recovery of Function; Regeneration; Stroke Volume; Time Factors; Ventricular Function, Left
PubMed: 26667804
DOI: 10.1186/s12872-015-0162-6 -
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 -
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 -
Basic & Clinical Pharmacology &... Apr 2020The high prevalence of statin and clarithromycin utilization creates potential for overlapping use. The objectives of this MiniReview were to investigate the evidence... (Comparative Study)
Comparative Study
The high prevalence of statin and clarithromycin utilization creates potential for overlapping use. The objectives of this MiniReview were to investigate the evidence base for drug-drug interactions between clarithromycin and currently marketed statins and to present management strategies for these drug combinations. We conducted a systematic literature review following PRISMA guidelines with English language studies retrieved from PubMed and EMBASE (from inception through March 2019). We included 29 articles (16 case reports, 5 observational, 5 clinical pharmacokinetic and 3 in vitro studies). Based on mechanistic/clinical studies involving clarithromycin or the related macrolide erythromycin (both strong inhibitors of CYP3A4 and of hepatic statin uptake transporters OATP1B1 and OATP1B3), clarithromycin is expected to substantially increase systemic exposure to simvastatin and lovastatin (>5-fold increase in area under the plasma concentration-time curve (AUC)), moderately increase AUCs of atorvastatin and pitavastatin (2- to 4-fold AUC increase) and slightly increase pravastatin exposure (≈2-fold AUC increase) while having little effect on fluvastatin or rosuvastatin. The 16 cases of statin-clarithromycin adverse drug reactions (rhabdomyolysis (n = 14) or less severe clinical myopathy) involved a CYP3A4-metabolized statin (simvastatin, lovastatin or atorvastatin). In line, a cohort study found concurrent use of clarithromycin and CYP3A4-metabolized statins to be associated with a doubled risk of hospitalization with rhabdomyolysis or other statin-related adverse events as compared with azithromycin-statin co-administration. If clarithromycin is necessary, we recommend (a) avoiding co-administration with simvastatin, lovastatin or atorvastatin; (b) withholding or dose-reducing pitavastatin; (c) continuing pravastatin therapy with caution, limiting pravastatin dose to 40 mg daily; and (d) continuing fluvastatin or rosuvastatin with caution.
Topics: Area Under Curve; Clarithromycin; Drug Interactions; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rhabdomyolysis
PubMed: 31628882
DOI: 10.1111/bcpt.13343 -
Medicine Jun 2021Atorvastatin treatment has been suggested as a therapeutic method for women with polycystic ovary syndrome (PCOS) in many clinical studies. Nonetheless, the effects of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atorvastatin treatment has been suggested as a therapeutic method for women with polycystic ovary syndrome (PCOS) in many clinical studies. Nonetheless, the effects of atorvastatin on insulin resistance in PCOS patients still remain controversial.
OBJECTIVE
The aim of this report was to evaluate the effects of atorvastatin therapy on the insulin resistance in the treatment of PCOS compared to that of placebo, in order to confer a reference for clinical practice.
METHODS
Randomized controlled trials (RCTs) of atorvastatin for PCOS published up to August, 2020 were searched. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated, and heterogeneity was measured by the I2 test. Sensitivity analysis was also carried out. The outcomes of interest were as follows: fasting glucose concentration, fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR) or body mass index (BMI) value.
RESULTS
Nine RCTs with 406 participants were included. The difference of fasting glucose concentration in PCOS patients between atorvastatin group and placebo group was not statistically significant (8 trials; SMD -0.06, 95% CI -0.31 to 0.20, P = .66). PCOS patients in atorvastatin group had lower fasting insulin level than those in placebo group (7 trials; SMD -1.84, 95% CI -3.06 to -0.62, P < .003). The homeostasis model assessment of insulin resistance (HOMA-IR) value showed significant decrease in the atorvastatin therapy compared to placebo (6 trials; SMD -4.12, 95% CI -6.00 to -2.23, P < .0001). In contrast to placebo, atorvastatin therapy did not decrease the BMI value significantly in PCOS patients (7 trials; SMD 0.12, 95% CI -0.07 to 0.31, P = .22).
CONCLUSIONS
Atorvastatin therapy can reduce insulin resistance in the treatment of patients with PCOS. In addition, further large-sample, multi-center RCTs are needed to identify these findings.
Topics: Adolescent; Adult; Atorvastatin; Blood Glucose; Body Mass Index; Fasting; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin; Insulin Resistance; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Treatment Outcome; Young Adult
PubMed: 34128863
DOI: 10.1097/MD.0000000000026289 -
The Cochrane Database of Systematic... Nov 2016Fibrates are effective for modifying atherogenic dyslipidaemia, and particularly for lowering serum triglycerides. However, evidence that fibrates reduce mortality and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fibrates are effective for modifying atherogenic dyslipidaemia, and particularly for lowering serum triglycerides. However, evidence that fibrates reduce mortality and morbidity associated with cardiovascular disease (CVD), or overall mortality and morbidity, in the primary prevention of CVD is lacking.
OBJECTIVES
This Cochrane Review and meta-analysis aimed to evaluate the clinical benefits and harms of fibrates versus placebo or usual care or fibrates plus other lipid-modifying drugs versus other lipid-modifying drugs alone for the primary prevention of cardiovascular disease (CVD) morbidity and mortality.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO), and Web of Science (all from inception to 19 May 2016). We searched four clinical trial registers (last searched on 3 August 2016) with the help of an experienced professional librarian. We searched the databases to identify randomised controlled trials (RCTs) evaluating the clinical effects of fibrate therapy in the primary prevention of CVD events. We did not impose any language restrictions.
SELECTION CRITERIA
We aimed to include all RCTs comparing the effects of fibrate monotherapy versus placebo or usual care, or fibrates plus other lipid-modifying drugs versus other lipid-modifying drugs alone. Included studies had a follow-up of at least six months for the primary prevention of CVD events. We excluded trials with clofibrate, because it was withdrawn from the market in 2002.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles and abstracts for potential study inclusion. Two review authors independently retrieved the full-text papers and extracted data. Disagreements were resolved by consensus. We calculated risk ratios (RRs) and accompanying 95% confidence intervals (CIs) for aggregate data on primary and secondary outcomes. We tested for heterogeneity with the Cochrane Q-test and used the I statistic to measure inconsistency of treatment effects across studies. Using the GRADE approach, we assessed the quality of the evidence and used the GRADE profiler software (GRADEpro GDT) to import data from Review Manager 5 to create 'Summary of findings' tables.
MAIN RESULTS
We identified six eligible trials including 16,135 individuals. The mean age of trial populations varied across trials; between 47.3 and 62.3 years. Four trials included individuals with diabetes mellitus type 2 only. The mean treatment duration and follow-up of participants across trials was 4.8 years. We judged the risks of selection and performance bias to be low; risks of detection bias, attrition bias, and reporting bias were unclear. Reporting of adverse effects by included trials was very limited; that is why we used discontinuation of therapy due to adverse effects as a proxy for adverse effects. Patients treated with fibrates had a reduced risk for the combined primary outcome of CVD death, non-fatal myocardial infarction, or non-fatal stroke compared to patients on placebo (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.74 to 0.96; participants = 16,135; studies = 6; moderate-quality of evidence). For secondary outcomes we found RRs for fibrate therapy compared with placebo of 0.79 for combined coronary heart disease death or non-fatal myocardial infarction (95% CI 0.68 to 0.92; participants = 16,135; studies = 6; moderate-quality of evidence); 1.01 for overall mortality (95% CI 0.81 to 1.26; participants = 8471; studies = 5; low-quality of evidence); 1.01 for non-CVD mortality (95% CI 0.76 to 1.35; participants = 8471; studies = 5; low-quality of evidence); and 1.38 for discontinuation of therapy due to adverse effects (95% CI 0.71 to 2.68; participants = 4805; studies = 3; I = 74%; very low-quality of evidence). Data on quality of life were not available from any trial. Trials that evaluated fibrates in the background of statins (2 studies) showed no benefits in preventing cardiovascular events.
AUTHORS' CONCLUSIONS
Moderate-quality evidence suggests that fibrates lower the risk for cardiovascular and coronary events in primary prevention, but the absolute treatment effects in the primary prevention setting are modest (absolute risk reductions < 1%). There is low-quality evidence that fibrates have no effect on overall or non-CVD mortality. Very low-quality evidence suggests that fibrates are not associated with increased risk for adverse effects.
Topics: Atorvastatin; Bezafibrate; Cardiovascular Diseases; Clofibric Acid; Fenofibrate; Gemfibrozil; Humans; Hypolipidemic Agents; Middle Aged; Myocardial Infarction; Primary Prevention; Simvastatin; Stroke
PubMed: 27849333
DOI: 10.1002/14651858.CD009753.pub2