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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 -
The Cochrane Database of Systematic... Jul 2023Statins are lipid-lowering agents with pleiotropic actions. Experts have proposed that in addition to improving the dyslipidaemia associated with polycystic ovary... (Review)
Review
BACKGROUND
Statins are lipid-lowering agents with pleiotropic actions. Experts have proposed that in addition to improving the dyslipidaemia associated with polycystic ovary syndrome (PCOS), statins may also exert other beneficial metabolic and endocrine effects, such as reducing testosterone levels. This is an update of a Cochrane Review first published in 2011.
OBJECTIVES
To assess the efficacy and safety of statin therapy in women with PCOS who are not actively trying to conceive.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHLs, and four ongoing trials registers on 7 November 2022. We also handsearched relevant conference proceedings and the reference lists of relevant trials for any additional studies, and we contacted experts in the field for any further ongoing studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that evaluated the effects of statin therapy in women with PCOS not actively trying to conceive. Eligible comparisons were statin versus placebo or no treatment, statin plus another agent versus the other agent alone, and statin versus another agent. We performed statistical analysis using Review Manager 5, and we assessed the certainty of the evidence using GRADE methods.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology. Our primary outcomes were resumption of menstrual regularity and resumption of spontaneous ovulation. Our secondary outcomes were clinical and physiological measures including hirsutism, acne severity, testosterone levels, and adverse events.
MAIN RESULTS
Six RCTs fulfilled the criteria for inclusion. They included 396 women with PCOS who received six weeks, three months, or six months of treatment; 374 women completed the studies. Three studies evaluated the effects of simvastatin and three studies evaluated the effects of atorvastatin. We summarised the results of the studies under the following comparisons. Statins versus placebo (3 RCTs) One trial measured resumption of menstrual regularity as menstrual cycle length in days. We are uncertain if statins compared with placebo shorten the mean length of the menstrual cycle (mean difference (MD) -2.00 days, 95% confidence interval (CI) -24.86 to 20.86; 37 participants; very low-certainty evidence). No studies reported resumption of spontaneous ovulation, improvement in hirsutism, or improvement in acne. We are uncertain if statins compared with placebo reduce testosterone levels after six weeks (MD 0.06, 95% CI -0.72 to 0.84; 1 RCT, 20 participants; very low-certainty evidence), after 3 months (MD -0.53, 95% CI -1.61 to 0.54; 2 RCTs, 64 participants; very low-certainty evidence), or after 6 months (MD 0.10, 95% CI -0.43 to 0.63; 1 RCT, 28 participants; very low-certainty evidence) Two studies recorded adverse events, and neither reported significant differences between the groups. Statins plus metformin versus metformin alone (1 RCT) The single RCT included in this comparison measured resumption of menstrual regularity as the number of spontaneous menses per six months. We are uncertain if statins plus metformin compared with metformin improves resumption of menstrual regularity (MD 0.60 menses, 95% CI 0.08 to 1.12; 69 participants; very low-certainty evidence). The study did not report resumption of spontaneous ovulation. We are uncertain if statins plus metformin compared with metformin alone improves hirsutism measured using the Ferriman-Gallwey score (MD -0.16, 95% CI -0.91 to 0.59; 69 participants; very low-certainty evidence), acne severity measured on a scale of 0 to 3 (MD -0.31, 95% CI -0.67 to 0.05; 69 participants; very low-certainty evidence), or testosterone levels (MD -0.03, 95% CI -0.37 to 0.31; 69 participants; very low-certainty evidence). The study reported that no significant adverse events occurred. Statins plus oral contraceptive pill versus oral contraceptive pill alone (1 RCT) The single RCT included in this comparison did not report resumption of menstrual regularity or spontaneous ovulation. We are uncertain if statins plus the oral contraceptive pill (OCP) improves hirsutism compared with OCP alone (MD -0.12, 95% CI -0.41 to 0.17; 48 participants; very low-certainty evidence). The study did not report improvement in acne severity. We are also uncertain if statins plus OCP compared with OCP alone reduces testosterone levels, because the certainty of the evidence was very low (MD -0.82, 95% CI -1.38 to -0.26; 48 participants). The study reported that no participants experienced significant side effects. Statins versus metformin (2 RCTs) We are uncertain if statins improve menstrual regularity compared with metformin (number of spontaneous menses per six months) compared to metformin (MD 0.50 menses, 95% CI -0.05 to 1.05; 1 RCT, 61 participants, very low-certainty evidence). No studies reported resumption of spontaneous ovulation. We are uncertain if statins compared with metformin reduce hirsutism measured using the Ferriman-Gallwey score (MD -0.26, 95% CI -0.97 to 0.45; 1 RCT, 61 participants; very low-certainty evidence), acne severity measured on a scale of 0 to 3 (MD -0.18, 95% CI -0.53 to 0.17; 1 RCT, 61 participants; very low-certainty evidence), or testosterone levels (MD -0.24, 95% CI -0.58 to 0.10; 1 RCT, 61 participants; very low-certainty evidence). Both trials reported that no significant adverse events had occurred. Statins versus oral contraceptive pill plus flutamide (1 RCT) According to the study report, no participants experienced any significant side effects. There were no available data for any other main outcomes.
AUTHORS' CONCLUSIONS
The evidence for all main outcomes of this review was of very low certainty. Due to the limited evidence, we are uncertain if statins compared with placebo, or statins plus metformin compared with metformin alone, improve resumption of menstrual regularity. The trial evaluating statin plus OCP versus OCP alone reported neither of our primary outcomes. No other studies reported resumption of spontaneous ovulation. We are uncertain if statins improve hirsutism, acne severity, or testosterone. All trials that measured adverse events reported no significant differences between the groups.
Topics: Female; Humans; Polycystic Ovary Syndrome; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hirsutism; Metformin; Acne Vulgaris; Contraceptives, Oral; Testosterone
PubMed: 37462232
DOI: 10.1002/14651858.CD008565.pub3 -
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 -
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 -
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 -
European Journal of Internal Medicine Apr 2017
Meta-Analysis Review
Topics: Atorvastatin; Child; Cholesterol, LDL; Drug Administration Schedule; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myalgia; Randomized Controlled Trials as Topic; Rosuvastatin Calcium
PubMed: 28063659
DOI: 10.1016/j.ejim.2016.12.014 -
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 -
The Journal of Pharmacy and Pharmacology Apr 2023Peripheral neuropathy (PN), as an adverse reaction attributed to statin drugs, as well as the beneficial neuroprotective properties of statins, have been widely reported...
OBJECTIVES
Peripheral neuropathy (PN), as an adverse reaction attributed to statin drugs, as well as the beneficial neuroprotective properties of statins, have been widely reported and discussed in the literature. The aim of this study was to systematically review original publications that investigated the association of statin use and PN in diabetic and non-diabetic models, whether determined as a result of laboratory experimentation, or in a clinical setting.
KEY FINDINGS
A comprehensive search of the databases Google Scholar, PubMed/MEDLINE and Scopus was conducted. Sixty-six articles, which evaluated the link between statins and PN in either a clinical or in-vivo/in-vitro condition were included. Statin treatment in neuropathy-induced animal models demonstrates favourable neurological effects in both the morphological and functional aspects of neurons. However, an extended duration of statin treatment is minimally associated with the development of non-diabetic idiopathic neuropathy. Importantly, statins have the potential to regress diabetic PN through anti-inflammatory, anti-oxidant and immunomodulatory properties.
SUMMARY
When interpreting the results from studies that deal with the relationship between statins and PN, it is important to determine the mechanism(s) underlying the development of any potential neuropathies (in the presence or absence of diabetes), the type of model used (human or animal) and the duration of statin treatment.
Topics: Animals; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Diabetic Neuropathies; Diabetes Mellitus
PubMed: 36843566
DOI: 10.1093/jpp/rgac104 -
Thrombosis and Haemostasis Aug 2015D-dimers, specific breakdown fragments of cross-linked fibrin, are generally used as circulating markers of activated coagulation. Statins influence haemostatic factors,... (Meta-Analysis)
Meta-Analysis Review
D-dimers, specific breakdown fragments of cross-linked fibrin, are generally used as circulating markers of activated coagulation. Statins influence haemostatic factors, but their effect on plasma D-dimer levels is controversial. Therefore, the aim of this meta-analysis was to evaluate the association between statin therapy and plasma D-dimer levels. We searched PubMed, Web of Science, Cochrane Library, Scopus and EMBASE (up to September 25, 2014) to identify randomised controlled trials (RCTs) investigating the impact of statin therapy on plasma D-dimer levels. Two independent reviewers extracted data on study characteristics, methods and outcomes. Meta-analysis of data from nine RCTs with 1,165 participants showed a significant effect of statin therapy in reducing plasma D-dimer levels (standardised mean difference [SMD]: -0.988 µg/ml, 95 % confidence interval [CI]: -1.590 - -0.385, p=0.001). The effect size was robust in sensitivity analysis and omission of no single study significantly changed the overall estimated effect size. In the subgroup analysis, the effect of statins on plasma D-dimer levels was significant only in the subsets of studies with treatment duration ≥ 12 weeks (SMD: -0.761 µg/ml, 95 %CI: -1.163- -0.360; p< 0.001), and for lipophilic statins (atorvastatin and simvastatin) (SMD: -1.364 µg/ml, 95 % CI: -2.202- -0.526; p=0.001). Hydrophilic statins (pravastatin and rosuvastatin) did not significantly reduce plasma D-dimer levels (SMD: -0.237 µg/ml, 95 %CI: -1.140-0.665, p=0.606). This meta-analysis of RCTs suggests a decrease of plasma D-dimer levels after three months of statin therapy, and especially after treatment with lipophilic statins. Well-designed trials are required to validate these results.
Topics: Anticoagulants; Biomarkers; Blood Coagulation; Dyslipidemias; Fibrin Fibrinogen Degradation Products; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome
PubMed: 26017749
DOI: 10.1160/TH14-11-0937 -
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