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Autoimmunity Reviews Apr 2016Efficacy and safety of statin therapy in patients with systemic lupus erythematosus (SLE) is controversial. The aim of this meta-analysis was to evaluate whether statin... (Meta-Analysis)
Meta-Analysis Review
Statin impact on disease activity and C-reactive protein concentrations in systemic lupus erythematosus patients: A systematic review and meta-analysis of controlled trials.
BACKGROUND AND PURPOSE
Efficacy and safety of statin therapy in patients with systemic lupus erythematosus (SLE) is controversial. The aim of this meta-analysis was to evaluate whether statin therapy affects SLE disease activity and systemic inflammation (C-reactive protein, CRP) according to the evidence from controlled clinical trials.
EXPERIMENTAL APPROACH
A systematic review followed by a bibliographic search in Medline and SCOPUS (up to March 2015) was performed. Quantitative data synthesis was performed using a random-effects model and the generic inverse variance weighting method. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI).
KEY RESULTS
Meta-analysis of five controlled trials reporting statin impact on SLE disease activity did not suggest any significant effect of statin therapy on SLEDAI. Evaluation of seven controlled trials with reported effects on CRP levels suggested a significant reduction of plasma CRP concentrations in patients with SLE independent of the treatment duration. The effect size on plasma CRP concentrations was significant with lipophilic (atorvastatin) but not hydrophilic (pravastatin and rosuvastatin) statins.
CONCLUSION AND IMPLICATIONS
The present results suggest that statin therapy is likely to be safe in patients with SLE. In addition, statin-treated SLE patients may benefit from CRP reduction in terms of managing severe cardiovascular complications associated with the disease.
Topics: C-Reactive Protein; Controlled Clinical Trials as Topic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lupus Erythematosus, Systemic
PubMed: 26747436
DOI: 10.1016/j.autrev.2015.12.007 -
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 -
The Cochrane Database of Systematic... Dec 2011Multiple sclerosis (MS) 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 (MS) is an inflammatory demyelinating disease of the human central nervous system. Statins, prescribed as cholesterol lowering agents, have shown possible 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 METHODS
The Trials Search Coordinator searched the Cochrane MS Group Trials Register (1 August 2011). We searched the Chinese National Knowledge Infrastructure (CNKI) (1979 to 1 August 2011), trials registers and conference proceedings. Pharmaceutical companies and authors of included studies were contacted 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 for patients with MS.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed trial quality and extracted data.
MAIN RESULTS
Four trials involving 458 participants were included. All trials compared statins (two evaluating atorvastatin and two simvastatin) plus interferon beta-1a with interferon beta-1a alone for treating MS. The methodological quality was good for three studies and poor for remaining one. None 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, 12, 24 months follow up period. Statins 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.
AUTHORS' CONCLUSIONS
There is no convincing evidence to support the use of either atorvastatin or simvastatin as an adjunctive therapy in MS.
Topics: Atorvastatin; Disease Progression; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interferon-beta; Multiple Sclerosis; Pyrroles; Randomized Controlled Trials as Topic; Secondary Prevention; Simvastatin
PubMed: 22161428
DOI: 10.1002/14651858.CD008386.pub3 -
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 -
Drugs 2009The concomitant use of herbal medicines and pharmacotherapy is wide spread. We have reviewed the literature to determine the possible interactions between seven popular... (Review)
Review
The concomitant use of herbal medicines and pharmacotherapy is wide spread. We have reviewed the literature to determine the possible interactions between seven popular herbal medicines (ginkgo, St John's wort, ginseng, garlic, echinacea, saw palmetto and kava) and conventional drugs. Literature searches were performed using MEDLINE, Cochrane Library and EMBASE and we identified 128 case reports or case series, and 80 clinical trials. Clinical trials indicate that St John's wort (Hypericum perforatum), via cytochrome P450 (CYP) and/or P-glycoprotein induction, reduces the plasma concentrations (and/or increases the clearance) of alprazolam, amitriptyline, atorvastatin, chlorzoxazone, ciclosporin, debrisoquine, digoxin, erythromycin, fexofenadine, gliclazide, imatinib, indinavir, irinotecan, ivabradine, mephenytoin, methadone, midazolam, nifedipine, omeprazole, oral contraceptives, quazepam, simvastatin, tacrolimus, talinolol, verapamil, voriconazole and warfarin. Case reports or case series suggest interactions of St John's wort with adrenergic vasopressors, anaesthetics, bupropion, buspirone, ciclosporin, eletriptan, loperamide, nefazodone, nevirapine, oral contraceptives, paroxetine, phenprocoumon, prednisone, sertraline, tacrolimus, theophylline, tibolone, tryptophan, venlafaxine and warfarin. Ginkgo (Ginkgo biloba) decreases the plasma concentrations of omeprazole, ritonavir and tolbutamide. Clinical cases indicate interactions of ginkgo with antiepileptics, aspirin (acetylsalicylic acid), diuretics, ibuprofen, risperidone, rofecoxib, trazodone and warfarin. Ginseng (Panax ginseng) may interact with phenelzine and warfarin. Kava (Piper methysticum) increases the clearance of chlorzoxazone (a CYP2E1 substrate) and may interact with alprazolam, levodopa and paroxetine. Garlic (Allium sativum) interacts with chlorpropamide, fluindione, ritonavir and warfarin; it also reduces plasma concentrations of chlorzoxazone (a CYP2E1 probe). Echinacea might affect the clearance of caffeine (a CYP1A2 probe) and midazolam (a CYP3A4 probe). No interactions have been reported for saw palmetto (Serenoa repens). Numerous interactions between herbal medicines and conventional drugs have been documented. While the significance of many interactions is uncertain, several interactions, particularly those with St John's wort, may have serious clinical consequences.
Topics: Clinical Trials as Topic; Cytochrome P-450 Enzyme System; Herb-Drug Interactions; Humans
PubMed: 19719333
DOI: 10.2165/11317010-000000000-00000 -
Cardiovascular Drugs and Therapy Apr 2014Coronary reperfusion by primary percutaneous coronary intervention (PCI) has been established as an essential therapy of ST-elevation myocardial infarction (STEMI).... (Review)
Review
PURPOSE
Coronary reperfusion by primary percutaneous coronary intervention (PCI) has been established as an essential therapy of ST-elevation myocardial infarction (STEMI). Although the coronary intervention is undoubtedly beneficial, reperfusion itself can induce processes resulting in additional myocardial damage-a phenomenon known as ischemia-reperfusion injury (IRI). Oxidative stress is one of the major factors contributing to IRI. This systematic review focuses on the effect of antioxidant therapy on reperfusion triggered oxidative stress and myocardial IRI in patients with STEMI.
METHODS
We performed a systematic search in EMBASE and Pubmed and included eight randomised clinical trials evaluating edaravone, allopurinol, vitamin c, nicorandil, N-acetylcysteine, glucose-insulin-potassium, atorvastatin and deferoxamine.
RESULTS
Administration of edaravone, allopurinol, atorvastatin and nicorandil as a supplement to primary PCI significantly reduced oxidative stress and myocardial damage as well as improved cardiac function and clinical outcomes. Treatment with deferoxamine and N-acetylcysteine reduced the oxidative stress but an effect on the clinical outcome parameters could not be shown.
CONCLUSIONS
Preliminary studies of edaravone, allopurinol, atorvastatin and nicorandil seems promising though larger clinical trials with a wider range of clinical outcome parameters and trials of higher methodological quality should confirm the clinical benefits before a general recommendation can be given. Moreover, the included studies revealed a complex link between oxidative stress and cardiac function and/or cardiac adverse events and in order to further elucidate the detrimental role of oxidative stress in IRI in relation to primary PCI the assessment of oxidative stress and the clinical outcome parameters should be standardized.
Topics: Antioxidants; Humans; Myocardial Infarction; Myocardial Reperfusion; Myocardium; Oxidative Stress; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 24532094
DOI: 10.1007/s10557-014-6511-3 -
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 -
Pulmonary Circulation Sep 2016Statins improve pulmonary vascular remodeling and right ventricular hypertrophy in animal models of pulmonary arterial hypertension (PAH). However, clinical trials...
Statins improve pulmonary vascular remodeling and right ventricular hypertrophy in animal models of pulmonary arterial hypertension (PAH). However, clinical trials assessing the efficacy of statins in patients with PAH have reported mixed results. In this systematic review and meta-analysis, we assess the efficacy of statins in patients with PAH. We included randomized controlled clinical trials (RCTs) that evaluated the efficacy of statins in patients with PAH. Primary outcomes were mortality and change in 6-minute walk distance (6MWD). Data are presented as odds ratio (OR) and weighted mean difference (WMD), with 95% confidence intervals (CIs), for binary and continuous variables, respectively. We included 4 RCTs of high quality. The mean age of participants was 42 ± 13 years, and 70% were women. The statins used were simvastatin at 40-80 mg in two trials, atorvastatin 10 mg in one trial, and rosuvastatin 10 mg in the other. In the pooled-data analysis, there was no statistically significant improvement in mortality (OR: 0.75 [95% CI: 0.32-1.74]), 6MWD (WMD: -9.27 [95% CI: -27.73 to 9.20]), or cardiac index (WMD: 0.11 [95% CI: -0.04 to 0.27]) with statin therapy when compared to placebo. There was no difference in adverse events leading to withdrawal of therapy between statin and placebo groups. These data suggest that statins are not beneficial in the treatment of PAH. There is a need for large, well-conducted clinical trials assessing the effects of statins in patients with PAH. Future trials should include homogeneous patient populations and should be long-term, event-driven trials with combined morbidity and mortality end points.
PubMed: 27683606
DOI: 10.1086/687304 -
BMC Medicine Feb 2013Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates more than other lipid-modulating drugs, although evidence from... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates more than other lipid-modulating drugs, although evidence from randomized controlled trials also suggests that statins unexpectedly increase the risk of diabetes and improve immune function. Physiologically, statins would be expected to lower androgens because statins inhibit production of the substrate for the local synthesis of androgens and statins' pleiotropic effects are somewhat similar to the physiological effects of lowering testosterone, so we hypothesized that statins lower testosterone.
METHODS
A meta-analysis of placebo-controlled randomized trials of statins to test the a priori hypothesis that statins lower testosterone. We searched the PubMed, Medline and ISI Web of Science databases until the end of 2011, using '(Testosterone OR androgen) AND (CS-514 OR statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR rosuvastatin OR pravastatin)' restricted to randomized controlled trials in English, supplemented by a bibliographic search. We included studies with durations of 2+ weeks reporting changes in testosterone. Two reviewers independently searched, selected and assessed study quality. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting.
RESULTS
Of the 29 studies identified 11 were eligible. In 5 homogenous trials of 501 men, mainly middle aged with hypercholesterolemia, statins lowered testosterone by -0.66 nmol/l (95% confidence interval (CI) -0.14 to -1.18). In 6 heterogeneous trials of 368 young women with polycystic ovary syndrome, statins lowered testosterone by -0.40 nmol/l (95% CI -0.05 to -0.75). Overall statins lowered testosterone by -0.44 nmol/l (95% CI -0.75 to -0.13).
CONCLUSIONS
Statins may partially operate by lowering testosterone. Whether this is a detrimental side effect or mode of action warrants investigation given the potential implications for drug development and prevention of non-communicable chronic diseases. See commentary article here http://www.biomedcentral.com/1741-7015/11/58.
Topics: Adult; Aged; Anticholesteremic Agents; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Testosterone
PubMed: 23448151
DOI: 10.1186/1741-7015-11-57 -
Journal of Periodontal Research Jun 2018The cholesterol-lowering drugs, statins, possess anti-inflammatory, antimicrobial and pro-osteogenic properties, and thus have been tested as an adjunct to periodontal... (Meta-Analysis)
Meta-Analysis
The cholesterol-lowering drugs, statins, possess anti-inflammatory, antimicrobial and pro-osteogenic properties, and thus have been tested as an adjunct to periodontal treatment. The present systematic review aimed to answer the following focused research question: What is the effect of local and/or systemic statin use on periodontal tissues in preclinical in vivo studies of experimentally induced periodontitis (EIP) and/or acute/chronified periodontal defect (ACP) models? A literature search (of Medline/PubMed, Embase/Ovid, CENTRAL/Ovid) using the following main eligibility criteria was performed: (i) English or German language; (ii) controlled preclinical in vivo trials; (iii) local and/or systemic statin use in EIP and/or ACP models; and (iv) quantitative evaluation of periodontal tissues (i.e., alveolar bone level/amount, attachment level, cementum formation, periodontal ligament formation). Sixteen studies in EIP models and 7 studies in ACP models evaluated simvastatin, atorvastatin or rosuvastatin. Thirteen of the EIP (81%) and 2 of the ACP (29%) studies presented significantly better results in terms of alveolar bone level/amount in favor of statins. Meta-analysis based on 14 EIP trials confirmed a significant benefit of local and systemic statin use (P < .001) in terms of alveolar bone level/amount; meta-regression revealed that statin type exhibited a significant effect (P = .014) in favor of atorvastatin. Three studies reported a significantly higher periodontal attachment level in favor of statin use (P < .001). Complete periodontal regeneration was never observed; furthermore, statins did not exert any apparent effect on cementum formation. Neither local nor systemic use of statins resulted in severe adverse effects. Statin use in periodontal indications has a positive effect on periodontal tissue parameters, supporting the positive results already observed in clinical trials. Nevertheless, not all statins available have been tested so far, and further research is needed to identify the maximum effective concentration/dose and optimal carrier.
Topics: Animals; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Periodontitis; Randomized Controlled Trials as Topic
PubMed: 29211309
DOI: 10.1111/jre.12514