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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 -
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 -
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 -
Nutrition in Clinical Practice :... Apr 2013Extensive media coverage of the potential health benefits of vitamin D supplementation has translated into substantial increases in supplement sales over recent years.... (Review)
Review
Extensive media coverage of the potential health benefits of vitamin D supplementation has translated into substantial increases in supplement sales over recent years. Yet, the potential for drug-vitamin D interactions is rarely considered. This systematic review of the literature was conducted to evaluate the extent to which drugs affect vitamin D status or supplementation alters drug effectiveness or toxicity in humans. Electronic databases were used to identify eligible peer-reviewed studies published through September 1, 2010. Study characteristics and findings were abstracted, and quality was assessed for each study. A total of 109 unique reports met the inclusion criteria. The majority of eligible studies were classified as class C (nonrandomized trials, case-control studies, or time series) or D (cross-sectional, trend, case report/series, or before-and-after studies). Only 2 class C and 3 class D studies were of positive quality. Insufficient evidence was available to determine whether lipase inhibitors, antimicrobial agents, antiepileptic drugs, highly active antiretroviral agents, or H2 receptor antagonists alter serum 25(OH)D concentrations. Atorvastatin appears to increase 25(OH)D concentrations, whereas concurrent vitamin D supplementation decreases concentrations of atorvastatin. Use of thiazide diuretics in combination with calcium and vitamin D supplements may cause hypercalcemia in the elderly or those with compromised renal function or hyperparathyroidism. Larger studies with stronger study designs are needed to clarify potential drug-vitamin D interactions, especially for drugs metabolized by cytochrome P450 3A4 (CYP3A4). Healthcare providers should be aware of the potential for drug-vitamin D interactions.
Topics: Dietary Supplements; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Humans; Hypercalcemia; Hyperparathyroidism; Pharmaceutical Preparations; Vitamin D; Vitamins
PubMed: 23307906
DOI: 10.1177/0884533612467824 -
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 -
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 -
Frontiers in Pharmacology 2022This network meta-analysis aimed to explore the effect of different drugs on mortality and neurological improvement in patients with traumatic brain injury (TBI), and...
This network meta-analysis aimed to explore the effect of different drugs on mortality and neurological improvement in patients with traumatic brain injury (TBI), and to clarify which drug might be used as a more promising intervention for treating such patients by ranking. We conducted a comprehensive search from PubMed, Medline, Embase, and Cochrane Library databases from the establishment of the database to 31 January 2022. Data were extracted from the included studies, and the quality was assessed using the Cochrane risk-of-bias tool. The primary outcome measure was mortality in patients with TBI. The secondary outcome measures were the proportion of favorable outcomes and the occurrence of drug treatment-related side effects in patients with TBI in each drug treatment group. Statistical analyses were performed using Stata v16.0 and RevMan v5.3.0. We included 30 randomized controlled trials that included 13 interventions (TXA, EPO, progesterone, progesterone + vitamin D, atorvastatin, beta-blocker therapy, Bradycor, Enoxaparin, Tracoprodi, dexanabinol, selenium, simvastatin, and placebo). The analysis revealed that these drugs significantly reduced mortality in patients with TBI and increased the proportion of patients with favorable outcomes after TBI compared with placebo. In terms of mortality after drug treatment, the order from the lowest to the highest was progesterone + vitamin D, beta-blocker therapy, EPO, simvastatin, Enoxaparin, Bradycor, Tracoprodi, selenium, atorvastatin, TXA, progesterone, dexanabinol, and placebo. In terms of the proportion of patients with favorable outcomes after drug treatment, the order from the highest to the lowest was as follows: Enoxaparin, progesterone + vitamin D, atorvastatin, simvastatin, Bradycor, EPO, beta-blocker therapy, progesterone, Tracoprodi, TXA, selenium, dexanabinol, and placebo. In addition, based on the classification of Glasgow Outcome Scale (GOS) scores after each drug treatment, this study also analyzed the three aspects of good recovery, moderate disability, and severe disability. It involved 10 interventions and revealed that compared with placebo treatment, a higher proportion of patients had a good recovery and moderate disability after treatment with progesterone + vitamin D, Bradycor, EPO, and progesterone. Meanwhile, the proportion of patients with a severe disability after treatment with progesterone + vitamin D and Bradycor was also low. The analysis of this study revealed that in patients with TBI, TXA, EPO, progesterone, progesterone + vitamin D, atorvastatin, beta-blocker therapy, Bradycor, Enoxaparin, Tracoprodi, dexanabinol, selenium, and simvastatin all reduced mortality and increased the proportion of patients with favorable outcomes in such patients compared with placebo. Among these, the progesterone + vitamin D had not only a higher proportion of patients with good recovery and moderate disability but also a lower proportion of patients with severe disability and mortality. However, whether this intervention can be used for clinical promotion still needs further exploration.
PubMed: 36408253
DOI: 10.3389/fphar.2022.1021653 -
Journal of Neurotrauma Aug 2011An increasing number of therapies for spinal cord injury (SCI) are emerging from the laboratory and seeking translation into human clinical trials. Many of these are... (Review)
Review
An increasing number of therapies for spinal cord injury (SCI) are emerging from the laboratory and seeking translation into human clinical trials. Many of these are administered as soon as possible after injury with the hope of attenuating secondary damage and maximizing the extent of spared neurologic tissue. In this article, we systematically review the available pre-clinical research on such neuroprotective therapies that are administered in a non-invasive manner for acute SCI. Specifically, we review treatments that have a relatively high potential for translation due to the fact that they are already used in human clinical applications, or are available in a form that could be administered to humans. These include: erythropoietin, NSAIDs, anti-CD11d antibodies, minocycline, progesterone, estrogen, magnesium, riluzole, polyethylene glycol, atorvastatin, inosine, and pioglitazone. The literature was systematically reviewed to examine studies in which an in-vivo animal model was utilized to assess the efficacy of the therapy in a traumatic SCI paradigm. Using these criteria, 122 studies were identified and reviewed in detail. Wide variations exist in the animal species, injury models, and experimental designs reported in the pre-clinical literature on the therapies reviewed. The review highlights the extent of investigation that has occurred in these specific therapies, and points out gaps in our knowledge that would be potentially valuable prior to human translation.
Topics: Animals; Disease Models, Animal; Humans; Neuroprotective Agents; Spinal Cord Injuries; Treatment Outcome
PubMed: 20146558
DOI: 10.1089/neu.2009.1149 -
Journal of Neurotrauma Aug 2011An increasing number of therapies for spinal cord injury (SCI) are emerging from the laboratory and seeking translation into human clinical trials. Many of these are... (Review)
Review
An increasing number of therapies for spinal cord injury (SCI) are emerging from the laboratory and seeking translation into human clinical trials. Many of these are administered as soon as possible after injury with the hope of attenuating secondary damage and maximizing the extent of spared neurologic tissue. In this article, we systematically reviewed the available preclinical research on such neuroprotective therapies that are administered in a non-invasive manner for acute SCI. Specifically, we reviewed treatments that have a relatively high potential for translation due to the fact that they are already used in human clinical applications or are available in a form that could be administered to humans. These included: erythropoietin, NSAIDs, anti-CD11d antibodies, minocycline, progesterone, estrogen, magnesium, riluzole, polyethylene glycol, atorvastatin, inosine, and pioglitazone. The literature was systematically reviewed to examine studies in which an in vivo animal model was utilized to assess the efficacy of the therapy in a traumatic spinal cord injury paradigm. Using these criteria, 122 studies were identified and reviewed in detail. Wide variations exist in the animal species, injury models, and experimental designs reported in the preclinical literature on the therapies reviewed. The review highlights the extent of investigation that has occurred in these specific therapies, and points out gaps in our knowledge that would be potentially valuable prior to human translation.
Topics: Animals; Antibodies, Monoclonal; Disease Models, Animal; Humans; Myelin Proteins; Nogo Proteins; Spinal Cord Injuries; Treatment Outcome
PubMed: 20082560
DOI: 10.1089/neu.2009.1150 -
Frontiers in Cardiovascular Medicine 2022To explore the associations between different types and doses of statins and adverse events in secondary prevention of cardiovascular disease.
Associations between statins and adverse events in secondary prevention of cardiovascular disease: Pairwise, network, and dose-response meta-analyses of 47 randomized controlled trials.
OBJECTIVES
To explore the associations between different types and doses of statins and adverse events in secondary prevention of cardiovascular disease.
METHODS
We searched PubMed, Embase, and Cochrane databases for randomized controlled trials that compared statins with non-statin controls or different types or doses of statins. The primary outcomes included muscle condition, transaminase elevations, renal insufficiency, gastrointestinal discomfort, cancer, new onset or exacerbation of diabetes, cognitive impairment, and eye condition. We also analyzed myocardial infarction (MI), stroke, death from cardiovascular diseases (CVD), and all-cause death as the secondary outcomes to compare the potential harms with the benefits of statins. We conducted pairwise meta-analyses to calculate the odds ratio (OR) and 95% confidence intervals (CIs) for each outcome. Network meta-analyses were performed to compare the adverse effects of different statins. An Emax model was used to examine the dose-response relationships of the adverse effects of each statin.
RESULTS
Forty-seven trials involving 107,752 participants were enrolled and followed up for 4.05 years. Compared with non-statin control, statins were associated with an increased risk of transaminase elevations [OR 1.62 (95% CI 1.20 to 2.18)]. Statins decreased the risk of MI [OR 0.66 (95% CI 0.61 to 0.71), < 0.001], stroke [OR 0.78 (95% CI 0.72 to 0.84), < 0.001], death from CVD [OR 0.77 (95% CI 0.72 to 0.83), < 0.001] and all-cause death [OR 0.83 (95% CI 0.79 to 0.88), < 0.001]. Atorvastatin showed a higher risk of transaminase elevations than non-statin control [OR 4.0 (95% CI 2.2 to 7.6)], pravastatin [OR 3.49 (95% CI 1.77 to 6.92)] and simvastatin [OR 2.77 (95% CI 1.31 to 5.09)], respectively. Compared with atorvastatin, simvastatin was associated with a lower risk of muscle problems [OR 0.70 (95% CI 0.55 to 0.90)], while rosuvastatin showed a higher risk [OR 1.75 (95% CI 1.17 to 2.61)]. An Emax dose-response relationship was identified for the effect of atorvastatin on transaminase elevations.
CONCLUSION
Statins were associated with increased risks of transaminases elevations in secondary prevention. Our study provides the ranking probabilities of statins that can help clinicians make optimal decisions when there is not enough literature to refer to.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021285161].
PubMed: 36093163
DOI: 10.3389/fcvm.2022.929020