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The Cochrane Database of Systematic... Dec 2010Multiple sclerosis is an inflammatory demyelinating disease of the human central nervous system. Statins, prescribed as cholesterol lowering agents, have shown... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis is an inflammatory demyelinating disease of the human central nervous system. Statins, prescribed as cholesterol lowering agents, have shown beneficial effects for treating MS in experimental and preliminary clinical studies.
OBJECTIVES
To evaluate the efficacy and safety of statins administered alone or as add-on to approved treatments for MS.
SEARCH STRATEGY
We searched the Cochrane MS Group Trials Register (April 2010), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2010), MEDLINE (PubMed) (January 1966 to April 2010), EMBASE (January 1974 to April 2010), the Chinese Biomedical Database (CBM) (1979 to April 2010) and the Chinese National Knowledge Infrastructure (CNKI) (1979 to April 2010). We searched trials registers and conference proceedings and contacted pharmaceutical companies and authors of included studies included for additional information.There were no language restrictions.
SELECTION CRITERIA
Randomised controlled trials comparing statins with placebo, or comparing statins in combination with approved treatments alone in for patients with MS.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed trial quality and extracted data.
MAIN RESULTS
Two trials involving 71 participants were included. Both trials compared atorvastatin plus beta interferon with beta interferon alone for treating MS. Only one was assessed of good methodological quality while the other one of poor methodological quality. Neither of them showed statistically significant difference between both treatment groups in reducing relapses, preventing disease progression or developing new T2 or gadolinium-enhanced lesions on MRI after 9 or 24 months follow up period. When combined with beta interferon, atorvastatin resulted to be safe and well tolerated, no serious adverse effects were reported. Changes on quality of life after receiving statins were not reported in the trials. Six trials which assess simvastatin or atorvastatin monotherapy or added to beta interferon for MS are still ongoing or awaiting publication.
AUTHORS' CONCLUSIONS
There is insufficient evidence to support statins as an effective treatment for patients with MS. Future high quality randomised controlled trials are needed.Improvements in methodology in trials which are ongoing or awaiting publication, are required for meaningful synthesis of data.
Topics: Atorvastatin; Disease Progression; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interferon-beta; Multiple Sclerosis; Pyrroles; Randomized Controlled Trials as Topic; Secondary Prevention
PubMed: 21154395
DOI: 10.1002/14651858.CD008386.pub2 -
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 -
Asian Journal of Andrology 2014To evaluate the effect of statins for erectile dysfunction (ED), a systematic review of the literature was conducted in the Cochrane Library, Embase and PubMed from the... (Meta-Analysis)
Meta-Analysis Review
To evaluate the effect of statins for erectile dysfunction (ED), a systematic review of the literature was conducted in the Cochrane Library, Embase and PubMed from the inception of each database to June 2013. Only randomized controlled trials (RCTs) comparing treatment for ED with statins were identified. Placebo RCTs with the International Index of Erectile Function (IIEF) as the outcome measure were eligible for meta-analysis. A total of seven RCTs including two statins with a total of 586 patients strictly met our criteria for systematic review and five of them qualified for the meta-analysis. A meta-analysis using a random effects model showed that statins were associated with a significant increase in IIEF-5 scores (mean difference (MD): 3.27; 95% confidential interval (CI):1.51 to 5.02; P < 0.01) and an overall improvement of lipid profiles including total cholesterol (MD: -1.08; 95% CI: -1.68 to -0.48; P < 0.01), low-density lipoprotein (LDL) cholesterol (MD: -1.43; 95% CI: -2.07 to -0.79; P < 0.01), high-density lipoprotein (HDL) cholesterol (MD: 0.24; 95% CI: 0.13 to 0.35; P < 0.01) and triglycerides (TGs) (MD: -0.55; 95% CI: -0.61 to -0.48; P < 0.01). In summary, our study revealed positive consequences of these lipid-lowering drugs on erectile function, especially for nonresponders to phosphodiesterase type 5 inhibitors (PDE5Is). However, it has been reported that statin therapy may reduce levels of testosterone and aggravate symptoms of ED. Therefore, larger, well-designed RCTs are needed to investigate the double-edged role of statins in the treatment of ED.
Topics: Atorvastatin; Dyslipidemias; Endothelium, Vascular; Erectile Dysfunction; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Pyrroles; Randomized Controlled Trials as Topic; Simvastatin
PubMed: 24556747
DOI: 10.4103/1008-682X.123678 -
Neural Regeneration Research Jun 2012To assess the clinical efficacy and safety of atorvastatin in the treatment of Alzheimer's disease.
OBJECTIVE
To assess the clinical efficacy and safety of atorvastatin in the treatment of Alzheimer's disease.
DATA SOURCES
Medline (1948/2011-04), Embase (1966/2011-04), Cochrane Library (Issue 3, 2011), Chinese National Knowledge Infrastructure (1989/2011-04), and the Chinese Biomedical Literature Database (1979/2011-04) were searched for randomized clinical trials regardless of language. Abstracts of conference papers were manually searched. Furthermore, Current Controlled Trials (http://controlled-trials.com), Clinical Trials.gov (http://clinicaltrials.gov), and Chinese Clinical Trial Registry (http://www.chictr.org) were also searched. Key words included Alzheimer disease, dementia, cognition, affection, memory dysfunction, hydroxymethylglutaryl-CoA reductase inhibitors, atorvastatin and statins.
DATA SELECTION
Randomized controlled trials of grade A or B according to quality evaluation criteria of the Cochrane Collaboration were selected, in which atorvastatin and placebo were used to evaluate the effects of atorvastatin in the treatment of Alzheimer's disease. Study methodological quality was evaluated based on criteria described in Cochrane Reviewer's Handbook 5.0.1. Revman 5.1 software was used for data analysis.
MAIN OUTCOME MEASURES
Clinical efficacy, safety, withdrawal from the studies, and withdrawal due to adverse effects.
RESULTS
Two randomized controlled trials were included, one was scale A, and the other was scale B. All patients (n = 710, age range 50-90 years) were diagnosed as probable or possible mild to moderate Alzheimer's disease according to standard criteria and treated with atorvastatin 80 mg/d or placebo. There was no difference between the two groups in the final follow-up for Clinical Global Impression of Change scale (WMD = 0.13, 95%CI: -0.15 to 0.40), the Alzheimer's Disease Assessment Scale-cognitive subscale (WMD = 1.05, 95%CI: -3.06 to 6.05), Mini-Mental State Examination Scale (WMD = 0.77, 95%CI: -0.57 to 2.10), and the Neuropsychiatric Instrument (WMD = 2.07, 95%CI: -1.59 to 5.73). The rates of abnormal liver function, withdrawal from treatment, and withdrawal due to adverse effects were higher in the treatment group (OR = 7.86, 95%CI: 2.50-24.69; OR = 4.70, 95%CI: 2.61-8.44; and OR = 5.47, 95%CI: 3.01-9.94; respectively) compared with the placebo group.
CONCLUSION
There is insufficient evidence to recommend atorvastatin for the treatment of mild to moderate Alzheimer's disease, because there was no benefit on general function, cognitive function or mental/behavior abnormality outcome measures. Efficacy and safety need to be confirmed by larger and higher quality randomized controlled trials, especially for moderate to severe Alzheimer's disease, because results of this systematic review may be limited by selection bias, implementation bias, as well as measurement bias.
PubMed: 25657666
DOI: 10.3969/j.issn.1673-5374.2012.17.010 -
Journal of Clinical Rheumatology :... Jan 2022We queried the PubMed, Embase, Web of Science, and the CENTRAL (Cochrane Central Register of Controlled Trials) databases for this study. The pooled efficacy was... (Meta-Analysis)
Meta-Analysis
Efficacy of Atorvastatin Plus Conventional Disease-Modifying Antirheumatic Drugs on Disease Activity in Rheumatoid Arthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
METHODS
We queried the PubMed, Embase, Web of Science, and the CENTRAL (Cochrane Central Register of Controlled Trials) databases for this study. The pooled efficacy was evaluated using standardized mean differences. The inverse of the variance model was used for data pooling.
RESULTS
Based on the search, we identified 9 randomized controlled trials. The trials included 258 patients in the atorvastatin plus DMARD groups and 246 patients in the DMARD alone groups. The primary outcome was the change from baseline in the 2018 (209:228 Disease Activity Score in 28 Joints). Based on the Disease Activity Score in 28 Joints, disease activity in RA patients decreased significantly in patients given atorvastatin plus DMARD compared with patients given DMARD alone (standardized mean difference, -2.46; 95% confidence interval, -3.98 to -0.95; p = 0.0015; I2 = 97%; p < 0.01). Subgroup analysis did not identify any confounding factors, and no publication bias was detected in the meta-analysis.
CONCLUSIONS
The result supports that atorvastatin could be added to DMARDs to treat patients with RA.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Atorvastatin; Humans; Randomized Controlled Trials as Topic
PubMed: 33902096
DOI: 10.1097/RHU.0000000000001724 -
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 -
European Journal of Preventive... Aug 2013The extent to which individual statins vary in terms of clinical outcomes across all populations, in addition to secondary and primary prevention has not been studied... (Meta-Analysis)
Meta-Analysis Review
Comparative benefits of statins in the primary and secondary prevention of major coronary events and all-cause mortality: a network meta-analysis of placebo-controlled and active-comparator trials.
BACKGROUND
The extent to which individual statins vary in terms of clinical outcomes across all populations, in addition to secondary and primary prevention has not been studied extensively in meta-analyses.
METHODS
We systematically studied 199,721 participants in 92 placebo-controlled and active-comparator trials comparing atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin in participants with, or at risk of developing, cardiovascular disease. We performed pairwise and network meta-analyses for major coronary events and all-cause mortality outcomes, taking into account the dose differences across trials. Systematic review registration: PROSPERO 2011:CRD42011001470.
RESULTS
There were only a few trials that evaluated fluvastatin. Most frequent comparisons occurred between pravastatin and placebo, atorvastatin and placebo, and rosuvastatin and atorvastatin. No trial directly compared all six statins to each other. Across all populations, statins were significantly more effective than control in reducing all-cause mortality (OR 0.87, 95% credible interval 0.82-0.92) and major coronary events (OR 0.69, 95% CI 0.64-0.75). In terms of reducing major coronary events, atorvastatin (OR 0.66, 95% CI 0.48-0.94) and fluvastatin (OR 0.59, 95% CI 0.36-0.95) were significantly more effective than rosuvastatin at comparable doses. In participants with cardiovascular disease, statins significantly reduced deaths (OR 0.82, 95% CI 0.75-0.90) and major coronary events (OR 0.69, 95% CI 0.62-0.77). Atorvastatin was significantly more effective than pravastatin (OR 0.65, 95% CI 0.43-0.99) and simvastatin (OR 0.68, 95% CI 0.38-0.98) for secondary prevention of major coronary events. In primary prevention, statins significantly reduced deaths (OR 0.91, 95% CI 0.83-0.99) and major coronary events (OR 0.69, 95% CI 0.61-0.79) with no differences among individual statins. Across all populations, atorvastatin (80%), fluvastatin (79%), and simvastatin (62%) had the highest overall probability of being the best treatment in terms of both outcomes. Higher doses of atorvastatin and fluvastatin had the highest number of significant differences in preventing major coronary events compared with other statins. No significant heterogeneity or inconsistency was detected.
CONCLUSIONS
Statins significantly reduce the incidence of all-cause mortality and major coronary events as compared to control in both secondary and primary prevention. This analysis provides evidence for potential differences between individual statins, which are not fully explained by their low-density lipoprotein cholesterol-reducing effects. The observed differences between statins should be investigated in future prospective studies.
Topics: Controlled Clinical Trials as Topic; Coronary Disease; Dyslipidemias; Evidence-Based Medicine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Odds Ratio; Primary Prevention; Randomized Controlled Trials as Topic; Risk Factors; Secondary Prevention; Treatment Outcome
PubMed: 23447425
DOI: 10.1177/2047487313480435 -
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 -
Rheumatology International Sep 2015To evaluate the efficacy of current treatments for the Raynaud phenomenon (RP) in patients with systemic sclerosis (SSc), a systematic literature search was performed... (Review)
Review
To evaluate the efficacy of current treatments for the Raynaud phenomenon (RP) in patients with systemic sclerosis (SSc), a systematic literature search was performed using Medline, EMBASE, and Cochrane Central Register of Controlled Trials (from 1961 to October 2011). We included meta-analyses, systematic reviews, clinical trials, and high-quality cohort studies published in English or Spanish. Patient populations had to include adults diagnosed with limited cutaneous or diffuse SSc who had associated RP and/or digital ulcers under pharmacological treatment. Efficacy of treatments was evaluated based on: number of RP episodes, RP severity, episode-free time, ulcer improvement/healing, and appearance of new ulcers. We used the Jadad scale of methodological quality to evaluate the quality of randomized clinical trials, and the 2009 Oxford Centre for Evidence-Based Medicine classification for other studies. Of a total of 1617 studies identified, only 27 fulfilled inclusion criteria. Drugs received the following grade recommendations: Grade A for nifedipine, nicardipine, quinapril, IV iloprost, bosentan, tadalafil, and MQx-503; Grade B for beraprost, cicaprost, DMSO, cyclofenil, and atorvastatin; and Grade C for misoprostol, prazosin, OPC-2826, enalapril, sildenafil, antioxidant, and stanazolol. Calcium channel blockers, prostanoids, tadalafil, and bosentan received the highest recommendation level for their effectiveness. However, most systematic reviews reviewed just a handful of studies with small sample sizes and short follow-ups. Our review shows that the existing evidence on the efficacy of RP treatment in SSc patients is inconclusive which calls for further research, especially in the form of prospective studies of high quality with long-term follow-ups.
Topics: Humans; Raynaud Disease; Scleroderma, Systemic; Skin Ulcer; Treatment Outcome; Vasodilator Agents
PubMed: 25824427
DOI: 10.1007/s00296-015-3241-1 -
Drugs Jun 2016The aim of this study was to ascertain the effect size of statins in modulating plasma uric acid concentrations. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The aim of this study was to ascertain the effect size of statins in modulating plasma uric acid concentrations.
DATA SOURCES
A search was undertaken of the MEDLINE, SCOPUS, Web of Science and Google Scholar electronic databases.
STUDY SELECTION
Studies meeting the following criteria were included: (i) randomized controlled trials with either a parallel or crossover design; (ii) investigated the impact of statin therapy on plasma uric acid concentrations; and (iii) presentation of sufficient information on uric acid values at baseline and at the end of follow-up in each group, or presenting the net change.
DATA SYNTHESIS
The present meta-analysis suggested a significant reduction in plasma uric acid levels following statin therapy; however, this does not seem to be a class effect as subgroup analysis revealed a significant reduction with atorvastatin and simvastatin only, and not with pravastatin and rosuvastatin.
CONCLUSIONS
Atorvastatin and simvastatin, but not the other statins, can reduce serum uric acid levels.
Topics: Atorvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperuricemia; Randomized Controlled Trials as Topic; Simvastatin; Uric Acid
PubMed: 27260336
DOI: 10.1007/s40265-016-0591-2