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Neurosurgery Jul 2023The exacerbation of neurological outcomes often occurs in aneurysmal subarachnoid hemorrhage (aSAH). Statins have been commonly used for aSAH; however, there is lack of... (Meta-Analysis)
Meta-Analysis
Impacts of Statin Therapy Strategies on Incidence of Ischemic Cerebrovascular Events in Patients With Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Bayesian Network Meta-Analysis.
BACKGROUND
The exacerbation of neurological outcomes often occurs in aneurysmal subarachnoid hemorrhage (aSAH). Statins have been commonly used for aSAH; however, there is lack of evidence of the pharmacological efficacy of different dosages and types of statins.
OBJECTIVE
To apply the Bayesian network meta-analysis to analyze the optimal dosage and type of statins for the amelioration of ischemic cerebrovascular events (ICEs) in patients with aSAH.
METHODS
We developed the Bayesian network meta-analysis and systemic review to analyze the effects of statins on functional prognosis and the impacts of optimal dosage and type of statins on ICEs in patients with aSAH. The outcome variables of the analysis were the incidence of ICEs and functional prognosis.
RESULTS
A total of 2569 patients with aSAH across 14 studies were included. Analysis of 6 randomized controlled trials showed that statin use significantly improved functional prognosis in patients with aSAH (risk ratio [RR], 0.73; 95% CI, 0.55-0.97). Statins significantly reduced the incidence of ICEs (RR, 0.78; 95% CI, 0.67-0.90). Pravastatin (40 mg/d) decreased the incidence ICEs compared with placebo (RR, 0.14; 95% CI, 0.03-0.65) and was ranked the most effective, presenting with a significantly lower rate of the incidence ICEs than the worst-ranked simvastatin (40 mg/d) (RR, 0.13; 95% CI, 0.02-0.79).
CONCLUSION
Statins could significantly diminish the incidence of ICEs and enhance functional prognosis in patients with aSAH. Various types and dosages of statins show distinct efficacies.
Topics: Humans; Subarachnoid Hemorrhage; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Bayes Theorem; Network Meta-Analysis; Vasospasm, Intracranial
PubMed: 36794961
DOI: 10.1227/neu.0000000000002392 -
Cureus Sep 20213-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors are commonly used drugs in the management of elevated lipid levels and cardiovascular disease. In... (Review)
Review
3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors are commonly used drugs in the management of elevated lipid levels and cardiovascular disease. In cardiovascular diseases, among other common chronic conditions, inflammatory biomarkers are used to monitor disease progression and the risk of recurrent adverse events. We explored whether or not there was a positive effect on these biomarkers using HMG-CoA reductase inhibitors. The systematic review was conducted by gathering relevant papers mainly from three databases, identified through a generated Medical Subject Headings (MeSH) strategy. Identification of papers was subsequently followed by applying a selected inclusion and exclusion criteria to narrow the papers chosen for review. Post the application of stipulated criteria, 12 papers remained. They were subsequently assessed for risk of bias using a Cochrane risk analysis tool, identifying most as having some concerns of bias or low risk of bias. We found that HMG-CoA reductase inhibitors exhibit both a lipid-lowering effect addition to an anti-inflammatory effect.
PubMed: 34722051
DOI: 10.7759/cureus.18273 -
American Journal of Obstetrics and... Feb 2022There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying...
There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying disease pathophysiology. Molecular targets of candidate treatments include oxidative stress, antiangiogenic factors, and the angiotensin, nitric oxide, and proinflammatory pathways. The proposed treatments undergoing preclinical and clinical trial evaluation are thought to act on placental or endothelial disease or both. Most have adopted the pragmatic strategy of repurposing drugs. Of all the therapeutic agents proposed, pravastatin has received the most interest. There are preclinical studies showing that it has pleiotropic actions that favorably impact on multiple molecular targets and can resolve a preeclampsia phenotype in many animal models. An early phase clinical trial suggests that it may have therapeutic activity. Several large prevention trials are planned or ongoing and, when completed, could definitively address whether pravastatin can prevent preeclampsia. Proton-pump inhibitors, metformin, and sulfasalazine are other drugs with preclinical evidence of multiple molecular actions that could resolve the pathophysiology of preeclampsia. These agents are also currently being evaluated in clinical trials. There have been many recent preclinical studies identifying the potential of numerous natural compounds to treat preeclampsia, such as plant extracts and micronutrients that have potent anti-inflammatory or antioxidant activity. Recent preclinical studies have also proposed novel molecular-targeted strategies, such as monoclonal antibodies targeting tumor necrosis factor alpha, placental growth factor, and short interfering RNA technology, to silence the gene expression of soluble fms-like tyrosine kinase-1 or angiotensinogen. Other treatment approaches that have transitioned to human trials (ranging from single-arm to phase III trials that have been completed or are ongoing) include folic acid, nitric oxide donors (such as L-arginine), recombinant antithrombin III, digoxin immune antigen-binding fragment, and melatonin. There have been case series showing the removal of circulating soluble fms-like tyrosine kinase-1 may help stabilize the disease and prolong pregnancy. Interestingly, there are case reports suggesting that monoclonal antibody eculizumab (complement inhibitor) may have therapeutic potential. If new agents are discovered that are proven to be effective in preventing or treating preeclampsia, the potential to improve global maternal and perinatal health will be significant.
Topics: Antibodies, Monoclonal; Antioxidants; Antithrombin III; Biological Products; Blood Component Removal; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Metformin; Micronutrients; Placenta Growth Factor; Plant Extracts; Pravastatin; Pre-Eclampsia; Pregnancy; Proton Pump Inhibitors; RNA, Small Interfering; Recombinant Proteins; Sulfasalazine; Vascular Endothelial Growth Factor Receptor-1
PubMed: 32946849
DOI: 10.1016/j.ajog.2020.09.014 -
Current Medicinal Chemistry Aug 2023The literature suggests that statins may increase superoxide dismutase (SOD) levels by different mechanisms. These effects may contribute to the antioxidant and...
BACKGROUND AND OBJECTIVE
The literature suggests that statins may increase superoxide dismutase (SOD) levels by different mechanisms. These effects may contribute to the antioxidant and anti-inflammatory effects of statins, which are thought to be beneficial in preventing cardiovascular events. However, there are also conflicting results concerning the effect of statins on SOD levels. The goal of this systematic review was to evaluate the effect of statin therapy on SOD activity.
METHODS
This systematic review was performed based on the PRISMA statement. The terms ("statin" or "HMG-CoA reductase inhibitor" OR "lipid-lowering agents" OR "Atorvastatin" OR "Simvastatin" OR "Pravastatin" OR "Fluvastatin" OR "Lovastatin") AND ("superoxide dismutase" OR "SOD" OR "anti-oxidative" OR "oxidative stress") were searched in database systems Google Scholar, PubMed/MEDLINE, and Scopus from inception to April 2022.
RESULTS
A total of 14 controlled clinical trials - 10 randomized and 4 non-randomized - were found to be eligible. Four studies measured SOD levels in plasma, six in serum, two in red blood cells, one in venous blood, and one on both red blood cells and venous blood matrices. Seven clinical trials used atorvastatin, six used simvastatin, and four used rosuvastatin. Six studies reported an increase in SOD activity, seven found no significant changes, and one showed a reduced SOD activity.
CONCLUSION
Our systematic review suggests that treatment with statins has a positive effect on SOD activity. However, evidence from further randomized controlled trials is required to confirm the potential antioxidant effect of statin therapy.
PubMed: 37653630
DOI: 10.2174/0929867331666230831145809 -
European Journal of Neurology Jun 2020Prevention of ischaemic stroke and cardiovascular events is an established benefit of statin therapy, but the effects of statin treatment on the accrual of magnetic... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Prevention of ischaemic stroke and cardiovascular events is an established benefit of statin therapy, but the effects of statin treatment on the accrual of magnetic resonance imaging (MRI) markers of ischaemic cerebral injury remain unknown. A systematic review was performed to identify all studies that randomized patients with cardiovascular risk factors to statin treatment and assessed the effect of statin treatment on covert infarcts (asymptomatic, evident only on neuroimaging) and white matter hyperintensity (WMH) accrual on MRI.
METHODS
A systematic review in MEDLINE and Scopus from inception to 23 October 2019 was performed. A random-effects model was used to calculate the pooled estimates of the crude risk ratios and standardized mean differences.
RESULTS
Data from three randomized controlled trials (1430 participants) were included evaluating the effect of rosuvastatin (10 mg/day) in 668 hypertensive patients older than 60 years of age over 5 years, pravastatin (40 mg/day) in 554 elderly people more than 70 years of age over 3 years and simvastatin (20 mg/day) in 208 patients with asymptomatic middle cerebral artery stenosis over 2 years. Patients randomized to statin treatment had decreased accrual of new covert infarcts (risk ratio 0.63, 95% confidence interval 0.46-0.88) during a mean follow-up of 2-6 years. Only one study reported WMH decreased volume change in patients randomized to statin treatment compared to patients randomized to non-statin treatment (standardized mean difference -1.17; 95% confidence interval -1.33, -1.00).
CONCLUSION
Our findings suggest that, in addition to stroke prevention, statin treatment can reduce the accrual of covert MRI markers of ischaemic cerebral injury.
Topics: Aged; Brain Ischemia; Cerebral Infarction; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic; Stroke
PubMed: 32133735
DOI: 10.1111/ene.14196 -
Andrology Sep 2021Statins constitute the mainstay of treatment in patients with hypercholesterolemia. However, their effect on semen parameters is unknown.
BACKGROUND
Statins constitute the mainstay of treatment in patients with hypercholesterolemia. However, their effect on semen parameters is unknown.
OBJECTIVE
This study aimed to systematically review the best available evidence regarding the effect of statins on ejaculate volume and sperm concentration, motility, morphology, or vitality.
MATERIALS/METHODS
A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases up to January 10, 2021. Either randomized-controlled trials or prospective cohorts, conducted in males with hypercholesterolemia, were included.
RESULTS
Four studies, published between 1992 and 2014, were eligible. The number of participants ranged from 8 to 120 (n = 161). Study duration ranged from 14 to 48 weeks. The type and dose of statin used were pravastatin 20-80 mg/day and simvastatin 20-40 mg/day. With regard to ejaculate volume (n = 3) and sperm concentration (n = 4), no effect was shown with either pravastatin or simvastatin. Regarding sperm motility, either an increase (n = 2; pravastatin, simvastatin), decrease (n = 1; pravastatin), or no effect (n = 1; pravastatin, simvastatin) was found. With respect to sperm morphology, either a decrease (n = 2; pravastatin, simvastatin) or no effect (n = 2; pravastatin, simvastatin) was shown. Concerning sperm vitality, a single study showed a decrease with simvastatin. Because of the high heterogeneity of the populations studied and the limited number of studies, a meta-analysis was not performed.
CONCLUSION
This is the first systematic review on the effect of statins on semen parameters. As there is no evidence for such a detrimental effect, no specific approach has to be suggested regarding the preservation of reproductive function in men with hypercholesterolemia.
Topics: Adult; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Pravastatin; Prospective Studies; Randomized Controlled Trials as Topic; Semen; Simvastatin; Sperm Motility
PubMed: 33998174
DOI: 10.1111/andr.13039 -
Pharmacological Research Mar 2021Recent studies have suggested that statins may be associated with a lower risk of recurrent venous thromboembolism (VTE). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recent studies have suggested that statins may be associated with a lower risk of recurrent venous thromboembolism (VTE).
METHODS
We systematically searched PubMed, Web of Science and Cochrane Library from inception until May 2020 to identify any eligible studies that reported the association between statin use and the risk of recurrent VTE, and conducted a comprehensive systematic review and meta-analysis (PROSPERO registration number: CRD42020190169) on this matter.
RESULTS
A total of 14 observational studies were included for qualitative review and 12 of them qualified for meta-analyses. The main meta-analysis found that statin use was associated with a lower risk of disease recurrence among patients with VTE (pooled adjusted HR: 0.76, 95% CI: 0.69-0.83), which was robust in sensitivity analyses and free of significant publication bias. Additionally, such association was present when restricting to periods after anticoagulation withdrawal (pooled adjusted HR: 0.78, 95% CI: 0.70-0.88) and when separately analyzing recurrent deep vein thrombosis (pooled adjusted HR: 0.71, 95% CI: 0.62-0.81) and recurrent pulmonary embolism (pooled adjusted HR: 0.80, 95% CI: 0.66-0.97; P = 0.027). Furthermore, statin use in patients with VTE was also found to be associated with a lower risk of all-cause mortality (adjusted HR: 0.65, 95% CI: 0.56-0.77), and possibly an even lower risk of bleeding (adjusted HR: 0.88, 95% CI: 0.73-1.07), albeit not statistically significant.
CONCLUSION
Statins have the potential to reduce recurrent events among patient with VTE. Randomized clinical trials to better explore the effect of statins in secondary prevention of VTE are warranted.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pulmonary Embolism; Recurrence; Risk Factors; Venous Thromboembolism; Venous Thrombosis
PubMed: 33412275
DOI: 10.1016/j.phrs.2020.105413 -
Frontiers in Pharmacology 2022Different treatment protocols have been employed to manage heparin/low-dose aspirin refractory or high-risk pregnancies in antiphospholipid antibody syndrome (APS)...
Different treatment protocols have been employed to manage heparin/low-dose aspirin refractory or high-risk pregnancies in antiphospholipid antibody syndrome (APS) pregnancies. A systematic review of the literature on additional treatments used in refractory and/or high-risk APS pregnancies was conducted. Records from February 2006 to October 2021 were retrieved from PubMed, Web of Science, Cochrane, and the www.clinicaltrials.gov platform. Twenty-one studies met our eligibility criteria. Live birth rate is this study's primary endpoint, while pregnancy complications and adverse events are secondary endpoints. A total of 434 pregnancies, 162 (37.3%) refractory and 272 (62.7%) high-risk/refractory pregnancies, were included. Both IVIG <2 gr/kg/monthly/HCQ/LDS and PEX/IA ± LDS led to 100% viable infants in refractory APS. Furthermore, HCQ 200-400 mg showed a higher live birth rate than HCQ + LDS (88.6% . 82.7%). Following treatment protocol with HCQ 200-400 mg and IVIG <2 gr/kg/monthly/HCQ/LDS, pregnancy complications rates of 16.7 and 83.3% were registered, respectively. Pravastatin 20 mg, IA weekly + IVIG 2 gr/monthly, and PEX weekly + IVIg 2 gr/kg/monthly showed higher live birth rates in high-risk APS pregnancies of 100, 100 and 92%, respectively, whereas the lower severe pregnancy complications were reported in pregnancies treated with PEX weekly + IVIg 2 gr/kg/monthly (11.1%). One (0.6%) case of dermatitis during treatment with HCQ was observed. The results of this study showed that HCQ 200-400 mg and PEX weekly + IVIG 2 gr/kg/monthly achieved a higher live birth rate in refractory APS and high-risk/refractory APS, respectively. The results presented provide clinicians with up-to-date knowledge in the management of APS pregnancies according to risk stratification.
PubMed: 35662738
DOI: 10.3389/fphar.2022.849692 -
European Journal of Clinical... Dec 2020A growing body of preclinical and observational research suggests that statins have potential as a therapeutic strategy in patients with cancer. This systematic review...
PURPOSE
A growing body of preclinical and observational research suggests that statins have potential as a therapeutic strategy in patients with cancer. This systematic review of randomised controlled trials (RCTs) in patients with solid tumours aimed to determine the efficacy of statin therapy on mortality outcomes, their safety profile and the risk of bias of included studies.
METHODS
Full-text articles comparing statin therapy versus control in solid tumours and reporting mortality outcomes were identified from Medline and Embase from conception to February 2020. A systematic review with qualitative (primarily) and quantitative synthesis was conducted. This systematic review was prospectively registered (Prospero registration CRD42018116364).
RESULTS
Eleven trials of 2165 patients were included. Primary tumour sites investigated included lung, colorectal, gastro-oesophageal, pancreatic and liver. Most trials recruited patients with advanced malignancy and used sub-maximal statin doses for relatively short durations. Aside from one trial which demonstrated benefit with allocation to pravastatin 40 mg in hepatocellular carcinoma, the remaining ten trials did not demonstrate efficacy with statins. The pooled hazard ratio for all-cause mortality with allocation to pravastatin in patients with hepatocellular carcinoma in two trials was 0.69 (95% confidence interval CI 0.30-1.61). Study estimates were imprecise. There were no clinically important differences in statin-related adverse events between groups. Overall, included trials were deemed low risk of bias.
CONCLUSION
The trial evidence is not sufficiently robust to confirm or refute the efficacy and safety of statins in patients with solid malignant tumours. Study and patient characteristics may explain this uncertainty. The potential role of high-dose statins in adjuvant settings deserves further research.
Topics: Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Neoplasms; Pravastatin; Progression-Free Survival; Randomized Controlled Trials as Topic; Time Factors
PubMed: 32719919
DOI: 10.1007/s00228-020-02967-0 -
Nutrients Jul 2020Statins and omega-3 supplementation have been recommended for cardiovascular disease prevention, but comparative effects have not been investigated. This study aimed to... (Comparative Study)
Comparative Study Meta-Analysis
Comparative Effect of Statins and Omega-3 Supplementation on Cardiovascular Events: Meta-Analysis and Network Meta-Analysis of 63 Randomized Controlled Trials Including 264,516 Participants.
Statins and omega-3 supplementation have been recommended for cardiovascular disease prevention, but comparative effects have not been investigated. This study aimed to summarize current evidence of the effect of statins and omega-3 supplementation on cardiovascular events. A meta-analysis and a network meta-analysis of 63 randomized controlled trials were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs) for the effects of specific statins and omega-3 supplementation compared with controls. Overall, the statin group showed significant risk reductions in total cardiovascular disease, coronary heart disease, myocardial infarction, and stroke; however, omega-3 supplementation significantly decreased the risks of coronary heart disease and myocardial infarction only, in the comparison with the control group. In comparison with omega-3 supplementation, pravastatin significantly reduced the risks of total cardiovascular disease (RR = 0.81, 95% CI = 0.72-0.91), coronary heart disease (RR = 0.75, 95% CI = 0.60-0.94), and myocardial infarction (RR = 0.71, 95% CI = 0.55-0.94). Risks of total cardiovascular disease, coronary heart disease, myocardial infarction, and stroke in the atorvastatin group were statistically lower than those in the omega-3 group, with RRs (95% CIs) of 0.80 (0.73-0.88), 0.64 (0.50-0.82), 0.75 (0.60-0.93), and 0.81 (0.66-0.99), respectively. The findings of this study suggest that pravastatin and atorvastatin may be more beneficial than omega-3 supplementation in reducing the risk of total cardiovascular disease, coronary heart disease, and myocardial infarction.
Topics: Aged; Atorvastatin; Cardiovascular Diseases; Coronary Disease; Dietary Supplements; Fatty Acids, Omega-3; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Myocardial Infarction; Network Meta-Analysis; Pravastatin; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome
PubMed: 32722395
DOI: 10.3390/nu12082218