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Journal of Drugs in Dermatology : JDD Dec 2023Porokeratosis is a group of disorders characterized by aberrant skin keratinization secondary to genetic alterations in the mevalonate pathway, which participates in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Porokeratosis is a group of disorders characterized by aberrant skin keratinization secondary to genetic alterations in the mevalonate pathway, which participates in cholesterol synthesis. While a rare disorder, malignant transformation to squamous cell carcinoma is seen in up to 11% of cases. Recently, topical cholesterol and topical statin therapy have been suggested as a pathogenesis-directed treatment for porokeratosis.
METHODS
A PubMed/MEDLINE and Embase literature search was performed using the search terms: "porokeratosis" AND "cholesterol" OR "lovastatin" OR "simvastatin" OR "atorvastatin" OR "fluvastatin" OR "pitavastatin" OR "pravastatin" OR "rosuvastatin" OR "statin." Peer-reviewed clinical trials, case series, and case reports of all porokeratosis subtypes were included.
RESULTS
Eleven articles were included in the systematic review and 9 articles in the meta-analysis. The systematic review consisted of an aggregate of 33 patients, most of whom (n=31, 93.9%) applied the treatment twice daily for an average of 9.4 weeks (median=8 weeks), with 93.9% (n=31) experiencing improvement or resolution of porokeratosis. Sixteen patients (48.5%) used lovastatin and 16 (48.5%) used simvastatin with concurrent cholesterol therapy. Mild adverse events including erythema and contact dermatitis were experienced by 12.1% of patients. Our meta-analysis yielded a random effects model supporting a robust reduction in porokeratosis severity (OR = .076, 95% CI [0.022, 0.262]).
CONCLUSION
This underpowered meta-analysis provides limited, preliminary evidence supporting the efficacy of topical cholesterol/statin therapy. Overall, quality studies and aggregated sample size are limited; future large clinical trials are needed to further elucidate the role of topical cholesterol/statin therapy in the treatment of porokeratosis. J Drugs Dermatol. 2023;22(12):1160-1165. doi:10.36849/JDD.7775.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Porokeratosis; Lovastatin; Simvastatin; Cholesterol
PubMed: 38051843
DOI: 10.36849/JDD.7775 -
Seminars in Arthritis and Rheumatism Feb 2021The most efficacious strategy to manage pregnant patients with antiphospholipid syndrome (APS) refractory to conventional heparin/low-dose aspirin treatment or at high... (Review)
Review
The efficacy and safety of second-line treatments of refractory and/or high risk pregnant antiphospholipid syndrome patients. A systematic literature review analyzing 313 pregnancies.
OBJECTIVE
The most efficacious strategy to manage pregnant patients with antiphospholipid syndrome (APS) refractory to conventional heparin/low-dose aspirin treatment or at high risk of adverse pregnancy outcomes has not been determined with any degree of certainty. The study set out to evaluate the efficacy and safety of the second-line treatments most frequently used in addition to conventional therapy, and the data were analyzed to identify which is/are associated to the best pregnancy outcomes.
METHODS
A systematic review of the literature on studies concerning second-line treatments for refractory and/or high risk pregnant APS women published between February 2006 and February 2020 was conducted. The records were retrieved by searching Medline via Pubmed, the Web of Science platform, the Cochrane library database and clinicaltrials.gov.
RESULTS
Fourteen studies met the eligibility criteria of the review: six retrospective cohort studies, one case-control, one case-series and six case reports. The results of single treatment protocols based upon hydroxychloroquine (HCQ), low-dose steroids (LDS), intravenous immunoglobulins (IVIG), plasma exchange (PE) or pravastatin and of combination protocols based upon HCQ+LDS, IVIG+LDS, PE+LDS and PE+IVIG used during 313 pregnancies in 303 APS women were analyzed and compared. The second-line treatments produced 261/313 (83.4%) live births; severe pregnancy complications were registered in 75/313 (24%) pregnancies. Drug side-effects were observed in 3/313 (0.9%) pregnancies. Statistical analysis identified a significantly higher live birth rate and/or a significantly lower number of severe complications in the pregnancies treated with IVIG, HCQ, pravastatin, PE+IVIG and PE+LDS.
CONCLUSION
Our results suggest using low-dose IVIG (< 2 g/Kg/month) or HCQ 400 mg/day starting before pregnancy in women with APS refractory to conventional therapy, while high-dose IVIG (2 g/Kg/month) associated with PE or alone in those with high risk±refractory APS.
Topics: Antiphospholipid Syndrome; Aspirin; Female; Humans; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Retrospective Studies
PubMed: 33360227
DOI: 10.1016/j.semarthrit.2020.10.001 -
PloS One 2022Disturbed cognitive function is associated with several causes of mortality; however, the association between cognitive function and the risk of cancer death has not... (Meta-Analysis)
Meta-Analysis
Association of cognitive function with increased risk of cancer death and all-cause mortality: Longitudinal analysis, systematic review, and meta-analysis of prospective observational studies.
BACKGROUND
Disturbed cognitive function is associated with several causes of mortality; however, the association between cognitive function and the risk of cancer death has not been extensively investigated yet. We aimed to evaluate the association of cognitive function with the risk of cancer death and all-cause mortality in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) and Leiden 85-plus Study. Additionally, a systematic review and meta-analysis of longitudinal studies were conducted to evaluate the association of cognitive function and risk of cancer death.
METHODS
Risk of cancer death and all-cause mortality were reported using hazard ratios (HRs) with 95% confidence interval (CI) in tertiles of cognitive function of PROSPER and Leiden85-Plus Study. Additionally, PubMed, Embase, Web of Science, Cochrane, PsycINFO, Academic Search Premier, CINHAL, and Emcare were searched up to November 1st, 2020 to perform a systematic review and meta-analysis. The relative risks (RRs) with 95%CI of cancer death per each standard deviation lower performance in cognitive measurements were calculated.
RESULTS
Participants of PROSPER had 1.65-fold (95%CI 1.11-2.47) greater risk of cancer death (P for trend = 0.016) and 1.85-fold (95%CI 1.46-2.34) higher risk of all-cause mortality (P for trend<0.001), in multivariable models. Results of the Leiden-85 Plus Study showed that subjects with MMSE score below 24 had a lower chance of cancer death (HR 0.79, 95%CI 0.36-1.70, P for trend = 0.820) but had 2.18-fold (95%CI 1.57-3.02) higher risk of all-cause mortality compared to the reference group (P for trend<0.001). Besides, the results of systematic review and meta-analysis showed that per each standard deviation lower performance in cognitive function, individuals were at a 10% higher chance of cancer death (RR 1.10, 95%CI 1.00-1.20, P-value = 0.044).
CONCLUSIONS
Lower cognitive function performance is associated with a marginally increased risk of cancer death, in line with a significantly greater risk of all-cause mortality.
Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Cognition; Cognitive Dysfunction; Female; Humans; Male; Neoplasms; Pravastatin; Prospective Studies
PubMed: 34995287
DOI: 10.1371/journal.pone.0261826 -
The Cochrane Database of Systematic... Nov 2019Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are affected. Those who are homozygous have severe disease. The average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500, although recent genetic epidemiological data from Denmark and next generation sequencing data suggest the frequency may be closer to 1 in 250. Diagnosis of familial hypercholesterolemia in children is based on elevated total cholesterol and low-density lipoprotein cholesterol levels or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong treatment, started in childhood, is needed to reduce the risk of cardiovascular disease. In children with the disease, diet was the cornerstone of treatment but the addition of lipid-lowering medications has resulted in a significant improvement in treatment. Anion exchange resins, such as cholestyramine and colestipol, were found to be effective, but they are poorly tolerated. Since the 1990s studies carried out on children aged 6 to 17 years with heterozygous familial hypercholesterolemia have demonstrated significant reductions in their serum total and low-density lipoprotein cholesterol levels. While statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. This is an update of a previously published version of this Cochane Review.
OBJECTIVES
To assess the effectiveness and safety of statins in children with heterozygous familial hypercholesterolemia.
SEARCH METHODS
Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline. Date of most recent search: 04 November 2019.
SELECTION CRITERIA
Randomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies for inclusion and extracted data.
MAIN RESULTS
We found 26 potentially eligible studies, of which we included nine randomized placebo-controlled studies (1177 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points (high-quality evidence). There may be little or no difference in liver function (serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations) between treated and placebo groups at any time point (low-quality evidence). There may be little or no difference in myopathy (as measured in change in creatinine levels) (low-quality evidence) or clinical adverse events (moderate-quality evidence) with statins compared to placebo. One study on simvastatin showed that this may slightly improve flow-mediated dilatation of the brachial artery (low-quality evidence), and on pravastatin for two years may have induced a regression in carotid intima media thickness (low-quality evidence). No studies reported rhabdomyolysis (degeneration of skeletal muscle tissue) or death due to rhabdomyolysis, quality of life or compliance to study medication.
AUTHORS' CONCLUSIONS
Statin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia. Few or no safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety remains unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.
Topics: Adolescent; Adult; Child; Cholesterol, LDL; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Male; Randomized Controlled Trials as Topic; Young Adult
PubMed: 31696945
DOI: 10.1002/14651858.CD006401.pub5 -
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 -
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 -
Cancer Causes & Control : CCC Oct 2020The link between lipid-stabilizing medications and epithelial ovarian carcinogenesis is incompletely understood. Statins may reduce ovarian cancer risk, but results are... (Meta-Analysis)
Meta-Analysis
PURPOSE
The link between lipid-stabilizing medications and epithelial ovarian carcinogenesis is incompletely understood. Statins may reduce ovarian cancer risk, but results are inconclusive.
METHODS
We conducted a systematic review and meta-analysis of studies reporting associations between statin use and ovarian cancer risk in PubMed. Summary risk ratios (RRs) and confidence intervals (CIs) were calculated. Subgroup analyses by cancer histotype, statin class (lipo- or hydrophilic) and duration of statin use were conducted. Use of individual statins in populations was assessed to determine population-specific differences in statin types.
RESULTS
Nine studies with 435,237 total women were included (1 randomized controlled trial (RCT); 4 prospective; 4 case-control). Statin use was associated with a reduced risk of ovarian cancer (RR 0.87, 95% CI 0.74-1.03) and risk was significantly reduced in populations with low pravastatin use (RR 0.83, 95% CI 0.70-0.99). Risk estimates varied by statin class (3 studies; lipophilic: RR 0.88, 95% CI 0.69-1.12; hydrophilic: RR 1.06, 95% CI 0.72-1.57) and cancer histotype (3 studies; serous: RR 0.95, 95% CI 0.69-1.30; clear cell: RR 1.17, 95% CI 0.74-1.86). Long-term use was associated with a reduced risk of ovarian cancer (RR 0.77, 95% CI 0.54-1.10) that further reduced when pravastatin use was low (RR 0.68, 95% CI 0.46-1.01). Between-study heterogeneity was high overall and in subgroups (I > 60%).
CONCLUSION
Statins may be associated with a reduced risk of ovarian cancer, but the effect likely differs by individual statin, duration of use and cancer histotype. Additional well-powered studies are needed to elucidate important subgroup effects.
Topics: Case-Control Studies; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ovarian Neoplasms; Prospective Studies; Randomized Controlled Trials as Topic; Risk
PubMed: 32685996
DOI: 10.1007/s10552-020-01327-8 -
American Journal of Obstetrics &... Feb 2024We aimed to perform a systematic review and meta-analysis of randomized controlled trials to evaluate the prophylactic use of pravastatin in pregnant women with... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We aimed to perform a systematic review and meta-analysis of randomized controlled trials to evaluate the prophylactic use of pravastatin in pregnant women with high-risk of preeclampsia.
DATA SOURCES
PubMed, Embase, Cochrane Central, and Web of Science were searched from inception to August 2023 with no language or filters restriction. The references from included studies, previous systematic reviews, and meta-analyses were manually searched for any additional studies.
STUDY ELIGIBILITY CRITERIA
Randomized controlled trials comparing pravastatin in any dose with placebo or no treatment in pregnant women with high risk for preeclampsia and up to 20 weeks of gestation were included in this meta-analysis.
METHODS
We used RStudio version 4.2.2 with random effects models to compute pooled risk ratios for prespecified outcomes data. The quality assessment was conducted using version 2 of the Cochrane Risk of Bias Assessment Tool. We also performed a trial sequential analysis to evaluate the reliability of our findings.
RESULTS
We included 3 randomized controlled trials comprising 213 patients, of whom 106 (49.8%) were allocated to the pravastatin group. There was no significant effect of pravastatin on the incidence of preeclampsia (risk ratio, 0.62; 95% confidence interval, 0.33-1.14; P=.12).
CONCLUSION
Our study was unable to demonstrate the benefit of pravastatin for preventing preeclampsia in high-risk pregnant women. Nevertheless, these findings comprised only preliminary studies with a small number of subjects, highlighting the need of well-designed, and adequately powered clinical trials.
Topics: Pregnancy; Humans; Female; Pre-Eclampsia; Pravastatin; Pregnant Women; Reproducibility of Results
PubMed: 38109997
DOI: 10.1016/j.ajogmf.2023.101260 -
Pharmacogenetics and Genomics Jun 2023Statins are the first-choice therapy for dyslipidemia, but their effectiveness can be influenced by genetic polymorphisms. This study was conducted to assess the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Statins are the first-choice therapy for dyslipidemia, but their effectiveness can be influenced by genetic polymorphisms. This study was conducted to assess the association of variants of the solute carrier anion transporter family 1B1 (SLCO1B1) gene, which encodes a transporter involving the hepatic clearance of the statins and their therapeutic efficacy.
METHOD
A systematic review was performed on four electronic databases to identify relevant studies. The pooled mean difference with 95% confidence interval (CI) in percentage change of concentration of LDL-C, total cholesterol (TC), HDL-C, and triglycerides was calculated. Heterogeneity between studies and publication bias, subgroup analyses, and sensitivity analyses were also carried out using R software.
RESULTS
Twenty-one studies on 24 365 participants and four variants [rs4149056 (c.521T>C), rs2306283 (c.388A>G), rs11045819 (c.463C>A), rs4363657 (g.89595T>C)] were analyzed. A statistically significant association was found between the LDL-C-lowering effectiveness and the rs4149056 and rs11045819 in the heterozygote model; and the rs4149056, rs2306283, and rs11045819 in the homozygote model. In the subgroup analyses, non-Asian populations, simvastatin, and pravastatin showed significant associations between LDL-C-lowering efficacy and the rs4149056 or rs2306283. Significant associations between the rs2306283 and HDL-C-increasing effectiveness were found in the homozygote model. Regarding TC-reducing, significant associations were observed in the heterozygote and homozygote models of the rs11045819. There was no heterogeneity and publication bias among most studies.
CONCLUSION
SLCO1B1 variants can be used as signals to predict the statins' effectiveness.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol, LDL; Polymorphism, Single Nucleotide; Liver-Specific Organic Anion Transporter 1; Simvastatin; Organic Anion Transporters
PubMed: 37098851
DOI: 10.1097/FPC.0000000000000490 -
American Journal of Kidney Diseases :... Jun 2016The effects of statin administration on kidney disease outcomes remain controversial. We undertook a systematic review and meta-analysis to assess the efficacy of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The effects of statin administration on kidney disease outcomes remain controversial. We undertook a systematic review and meta-analysis to assess the efficacy of statins on kidney outcomes.
STUDY DESIGN
We conducted a meta-analysis of randomized controlled trials (RCTs) using MEDLINE (1946 to August 31, 2015), EMBASE (1966 to August 31, 2015), and the Cochrane Library database (no date restriction).
SETTING & POPULATION
Adults who were not receiving dialysis, for whom kidney disease outcomes were reported.
SELECTION CRITERIA FOR STUDIES
RCTs in which statins were given for at least 6 months and kidney outcomes were measured.
INTERVENTION
Statins versus control, including placebo, usual care, and different types or doses of statins.
OUTCOMES
Kidney failure events, rate of change in estimated glomerular filtration rate (eGFR) per year, change in proteinuria or albuminuria, and, in patients with chronic kidney disease, major cardiovascular events.
RESULTS
57 eligible studies with 143,888 participants were included. Statin treatment did not produce an apparent beneficial effect for kidney failure events (OR, 0.98; 95% CI, 0.87-1.10; P=0.7) or end-stage renal disease events (OR, 0.98; 95% CI, 0.90-1.07; P=0.7). However, mean difference for rate of decline in eGFR (0.41 [95% CI, 0.11-0.70] mL/min/1.73m(2) per year slower in statin recipients) and standardized mean difference for change in proteinuria or albuminuria (-0.65 [95% CI, -0.94 to -0.37] standard deviation units, statin recipients vs controls) were statistically significant. In addition, statin therapy significantly reduced the risk for cardiovascular events (OR, 0.69; 95% CI, 0.61-0.79; P<0.001) in patients with chronic kidney disease.
LIMITATIONS
Inclusion of several post hoc analyses from large RCTs and substantial heterogeneity in secondary outcome analyses.
CONCLUSIONS
Statin therapy does not reduce the risk for kidney failure events in adults not receiving dialysis for whom kidney disease outcomes were reported, but may modestly reduce proteinuria and rate of eGFR decline.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Treatment Outcome
PubMed: 26905361
DOI: 10.1053/j.ajkd.2016.01.016