-
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 -
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 -
Annals of Translational Medicine Dec 2019Pulmonary hypertension (PH) is a multi-causal disease and no satisfactory therapeutic strategies for it. Statins have been suggested as potential drugs in PH, whose...
BACKGROUND
Pulmonary hypertension (PH) is a multi-causal disease and no satisfactory therapeutic strategies for it. Statins have been suggested as potential drugs in PH, whose effects in different clinic types of PH have not been conclusive. In this study, we included randomized controlled clinical trials (RCTs) evaluating the efficacy and safety of statins therapy in PH.
METHODS
We searched databases including Medline, Embase, Cochrane, PubMed and Web of science, with time up to January 1, 2019. With 95% confidence interval (CI), weighted mean difference (WMD) or standardized mean difference (SMD) was pooled and calculated in a random or fixed effect model according to I2 statistic.
RESULTS
A total of nine RCTs with 657 patients were included. Four types of statins (atorvastatin, pravastatin, rosuvastatin and simvastatin) were used at different doses (10-80 mg daily) for up to 6 months. In the pooled-data analysis, compared with placebo, there were significant improvements in pulmonary arterial pressure (PAP), in addition to low-density lipoprotein (LDL) in patients treated with statins, but not in 6-minute walking distance (6MWD), cardiac index (CDI). No more adverse events and all-cause mortality were revealed. Subgroup analysis indicated that statins could decrease PAP in the subtype of PH due to chronic obstructive pulmonary disease (COPD), but not pulmonary arterial hypertension (PAH).
CONCLUSIONS
This study indicates that statins can efficiently and safely reduce PAP in PH, especially in the subtype due to COPD. Further RCTs are needed to focus on the efficacy and safety of statin therapy in different subtypes of PH.
PubMed: 32042802
DOI: 10.21037/atm.2019.11.19 -
Asian Journal of Andrology 2017The aim of this study is to investigate the effect of statins type or even when grouping statins by hydrophilic or hydrophobic nature on prostate cancer risk. A... (Meta-Analysis)
Meta-Analysis Review
The aim of this study is to investigate the effect of statins type or even when grouping statins by hydrophilic or hydrophobic nature on prostate cancer risk. A literature search was performed without language restrictions using the databases of PubMed (1984.1-2015.3), MEDLINE (1984.1-2015.3), and EMBASE (1990.1-2015.3). Two independent reviewers appraised eligible studies and extracted data. Weighted averages were reported as relative risk (RR) with 95% confidence intervals (CI). Statistic heterogeneity scores were assessed with the standard Cochran's Q-test and I2 statistic. Publication bias was detected using the Begg's and Egger's tests. All statistical analyses were conducted by STATA version 10. Finally, fourteen studies were included in the meta-analysis. Both hydrophilic and hydrophobic statins showed no association with incidence of prostate cancer (RR = 1.00, 95% CI: 0.82-1.17; RR = 0.90, 95% CI: 0.73-1.08, respectively). Meanwhile, the risk of prostate cancer was not reduced in simvastatin (RR = 0.89, 95% CI: 0.72-1.05), pravastatin (RR = 1.02, 95% CI: 0.94-1.11), atorvastatin (RR = 0.89, 95% CI: 0.76-1.02), fluvastatin (RR = 0.99, 95% CI: 0.97-1.01), or lovastatin users (RR = 0.94, 95% CI: 0.79-1.08). The funnel plot showed that there was no publication bias. The results showed that statins had a neutral effect on prostate cancer risk; hydrophilic and hydrophobic statins as well as any subtype of statins did not affect the risk of prostate cancer.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Male; Prostatic Neoplasms; Risk
PubMed: 27924788
DOI: 10.4103/1008-682X.190327 -
Mayo Clinic Proceedings. Innovations,... Jun 2019To assess the effect of statins compared with placebo on the risk of developing hypertransaminasemia.
OBJECTIVE
To assess the effect of statins compared with placebo on the risk of developing hypertransaminasemia.
PATIENTS AND METHODS
We performed a systematic review of electronic databases and included articles published between January 1, 1965, and April 10, 2017. Randomized clinical trials (RCTs) comparing statins vs placebo were included. Odds ratios (ORs) were pooled in random-effect meta-analyses according to established methods recommended by the Cochrane Collaboration.
RESULTS
Seventy-three eligible RCTs, comprising 123,051 patients, were identified. Statins associated with a significantly risk of hypertransaminasemia (OR 1.45; 95% confidence interval [CI], 1.24-1.69; <.001). Atorvastatin showed the highest odds (OR 2.66; 95% CI, 1.74-4.06; <.001) followed by rosuvastatin (OR 1.35; 95% CI, 1.06-1.70; =.01) and lovastatin (OR 1.53; 95% CI, 1.03-2.28; =.04). Pravastatin, fluvastatin, and simvastatin yielded no statistically different odds compared with placebo.
CONCLUSIONS
A dose-dependent risk of developing hypertransaminasemia occurs in patients taking atorvastatin, rosuvastatin, and lovastatin.
PubMed: 31193835
DOI: 10.1016/j.mayocpiqo.2019.01.003 -
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 -
Thrombosis and Haemostasis Mar 2016Increased plasma levels of von Willebrand factor antigen (vWF:Ag) are associated with high risk of coronary artery disease. The effect of statin therapy on vWF:Ag levels... (Meta-Analysis)
Meta-Analysis Review
Increased plasma levels of von Willebrand factor antigen (vWF:Ag) are associated with high risk of coronary artery disease. The effect of statin therapy on vWF:Ag levels remains uncertain. Therefore the aim of this meta-analysis was to evaluate the effect of statin therapy on vWF:Ag Levels. A systematic multiple-database search was carried out to identify randomized controlled trials (RCTs) that investigated the effect of statins on plasma vWF:Ag levels. Random-effect meta-analysis of 21 treatment arms revealed a significant decrease in plasma vWF:Ag levels following statin therapy (SMD: -0.54, 95 %CI: -0.87, -0.21, p=0.001). In subgroup analyses, the greatest effect was observed with simvastatin (SMD: -1.54, 95 %CI: -2.92, -0.17, p=0.028) and pravastatin (SMD: -0.61, 95 %CI: -1.18, -0.04, p=0.035), but not with fluvastatin (SMD: -0.34, 95 %CI: -0.69, 0.02, p=0.065), atorvastatin (SMD: -0.23, 95 %CI: -0.57, 0.11, p=0.179) and rosuvastatin (SMD: -0.20, 95 % CI: -0.71, 0.30, p=0.431). The lowering effect of statins on plasma vWF:Ag levels was greater in the subset of studies lasting ≥ 12 weeks (SMD: -0.70, 95 %CI: -1.19, -0.22, p=0.005) compared with that of studies lasting < 12 weeks (SMD: -0.34, 95 %CI: -0.67, 0.003, p=0.052). Finally, low-intensity statin therapy was not associated with a significant reduction in vWF:Ag levels (SMD: -0.28, 95 %CI: -0.82, 0.27, p=0.320), but a significant effect was observed in high-intensity statin trials (SMD: -0.66, 95 %CI: -1.07, -0.24, p=0.002). This meta-analysis of available RCTs demonstrates a significant reduction in plasma vWF:Ag levels following statin therapy.
Topics: Adult; Aged; Antigens; Atherosclerosis; Atorvastatin; Cardiovascular Diseases; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Male; Middle Aged; Pravastatin; Randomized Controlled Trials as Topic; Regression Analysis; Risk Assessment; Rosuvastatin Calcium; Simvastatin; Thrombosis; Young Adult; von Willebrand Factor
PubMed: 26632869
DOI: 10.1160/TH15-08-0620 -
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 -
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 -
Pharmacological Research Sep 2015Statin therapy may lower plasma coenzyme Q10 (CoQ10) concentrations, but the evidence as to the significance of this effect is unclear. We assessed the impact of statin... (Meta-Analysis)
Meta-Analysis
Statin therapy may lower plasma coenzyme Q10 (CoQ10) concentrations, but the evidence as to the significance of this effect is unclear. We assessed the impact of statin therapy on plasma CoQ10 concentrations through the meta-analysis of available RCTs. The literature search included selected databases up to April 30, 2015. The meta-analysis was performed using either a fixed-effects or random-effect model according to I(2) statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). The data from 8 placebo-controlled treatment arms suggested a significant reduction in plasma CoQ10 concentrations following treatment with statins (WMD: -0.44 μmol/L, 95%CI: -0.52, -0.37, p<0.001). The pooled effect size was robust and remained significant in the leave-one-out sensitivity analysis. Subgroup analysis suggested that the impact of statins on plasma CoQ10 concentrations is significant for all 4 types of statins studied i.e. atorvastatin (WMD: -0.41 μmol/L, 95%CI: -0.53, -0.29, p<0.001), simvastatin (WMD: -0.47 μmol/L, 95% CI: -0.61, -0.33, p<0.001), rosuvastatin (WMD: -0.49 μmol/L, 95%CI: -0.67, -0.31, p<0.001) and pravastatin (WMD: -0.43 μmol/L, 95%CI: -0.69, -0.16, p=0.001). Likewise, there was no differential effect of lipophilic (WMD: -0.43 μmol/L, 95%CI: -0.53, -0.34, p<0.001) and hydrophilic statins (WMD: -0.47 μmol/L, 95%CI: -0.62, -0.32, p<0.001). With respect to treatment duration, a significant effect was observed in both subsets of trials lasting <12 weeks (WMD: -0.51 μmol/L, 95%CI: -0.64, -0.39, p<0.001) and ≥12 weeks (WMD: -0.40 μmol/L, 95%CI: -0.50, -0.30, p<0.001). The meta-analysis showed a significant reduction in plasma CoQ10 concentrations following treatment with statins. Further well-designed trials are required to confirm our findings and elucidate their clinical relevance.
Topics: Adult; Aged; Case-Control Studies; Double-Blind Method; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Placebo Effect; Randomized Controlled Trials as Topic; Ubiquinone
PubMed: 26192349
DOI: 10.1016/j.phrs.2015.07.008