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European Journal of Preventive... Apr 2024Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized by markedly elevated circulating low-density lipoprotein cholesterol (LDL-C) from birth....
AIMS
Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized by markedly elevated circulating low-density lipoprotein cholesterol (LDL-C) from birth. This review aimed to critically evaluate treatments for HoFH with respect to their efficacy, safety, accessibility, overall context and position within the treatment pathway.
METHODS
A mixed-methods review was undertaken to systematically identify and characterize primary interventional studies on HoFH, with a focus on LDL-C reduction as the primary outcome. Interventions assessed were ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), lomitapide, evinacumab, with or without LDL apheresis.
RESULTS
Twenty-six seminal studies reporting unique patient data were identified. Four studies were randomized controlled trials (RCTs) with the remainder being single-arm trials or observational registries. Data extracted were heterogeneous and not suitable for meta-analyses. Two RCTs, assessed at being low risk of bias, demonstrated PCSK9i were safe and moderately effective. An RCT demonstrated evinacumab was safe and effective in all HoFH subgroups. Lomitapide was reported to be efficacious in a single-arm trial, but issues with adverse events, tolerability, and adherence were identified. An RCT on ezetimibe showed it was moderately effective when combined with a statin. LDL apheresis was reported as effective, but its evidence base was at very high risk of bias. All interventions lowered LDL-C, but the magnitude of this, and certainty in the supporting evidence, varied.
CONCLUSION
In practice, multiple treatments are required to treat HoFH. The sequencing of these should be made on an individualized basis, with consideration made to the benefits of each intervention.
PubMed: 38640433
DOI: 10.1093/eurjpc/zwae144 -
American Journal of Cardiovascular... May 2024Statin therapy is considered the gold standard for treating hypercholesterolemia. This updated meta-analysis aims to compare the efficacy and safety of a... (Meta-Analysis)
Meta-Analysis
Comparative Safety and Efficacy of Low/Moderate-Intensity Statin plus Ezetimibe Combination Therapy vs. High-Intensity Statin Monotherapy in Patients with Atherosclerotic Cardiovascular Disease: An Updated Meta-Analysis.
AIM
Statin therapy is considered the gold standard for treating hypercholesterolemia. This updated meta-analysis aims to compare the efficacy and safety of a low/moderate-intensity statin in combination with ezetimibe compared with high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (ASCVD).
METHODS
A systematic search of two databases (PubMed and Cochrane CENTRAL) was conducted from inception to January 2023 and a total of 21 randomized clinical trials (RCTs) were identified and included in the analysis. Data were pooled using Hedges's g and a Mantel-Haenszel random-effects model to derive standard mean differences (SMDs) and 95% confidence intervals (Cis). The primary outcome studied was the effect of these treatments on lipid parameters and safety events.
RESULTS
The results revealed that combination therapy was more effective in reducing low-density lipoprotein cholesterol (LDL-C) levels (SMD= - 0.41; CI - 0.63 to - 0.19; P = 0.0002). There was no significant change in the levels of high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG), high-sensitivity C-reactive protein (hs-CRP), Apo A1, or Apo B. The safety of these treatments was assessed by the following markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine phosphokinase (CK), and a significant difference was only observed in CK (SMD: - 0.81; CI - 1.52 to - 0.10; P = 0.02).
CONCLUSION
This meta-analysis demonstrated that the use of low/moderate-intensity statin combination therapy significantly reduced LDL-C levels compared with high-intensity statin monotherapy, making it preferable for patients with related risks. However, further trials are encouraged to evaluate potential adverse effects associated with combined therapy.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ezetimibe; Drug Therapy, Combination; Atherosclerosis; Anticholesteremic Agents; Cholesterol, LDL; Randomized Controlled Trials as Topic; Cardiovascular Diseases; Hypercholesterolemia; Cholesterol, HDL
PubMed: 38578578
DOI: 10.1007/s40256-024-00642-8 -
Nutrition Reviews Apr 2024Several studies have investigated the relationship between serum vitamin D and dyslipidemia in children and adolescents, but the findings have been contradictory.
The association between serum vitamin D levels and abnormal lipid profile in pediatrics: A GRADE-assessed systematic review and dose-response meta-analysis of epidemiologic studies.
CONTEXT
Several studies have investigated the relationship between serum vitamin D and dyslipidemia in children and adolescents, but the findings have been contradictory.
OBJECTIVE
The current systematic review and dose-response meta-analysis investigated the serum vitamin D - dyslipidemia relationship in children and adolescents.
DATA SOURCES
ISI Web of Science, Scopus, MEDLINE (PubMed), EMBASE databases, and Google Scholar, were searched up to December 2022.
DATA EXTRACTION
Observational studies that investigated the odds of dyslipidemia in categories of serum vitamin D levels in children were included, and their data were extracted.
DATA ANALYSIS
Pooling of 17 effect sizes from 15 studies (39 342 participants) showed that subjects with higher serum vitamin D had 27% lower odds of hypertriglyceridemia (odds ratio [OR] = 0.73; 95% confidence interval [CI]: 0.60, 0.88). A meta-analysis of 18 effect sizes from 16 studies (39 718 participants) illustrated that highest vs lowest serum vitamin D was related to 22% lower odds of low high-density lipoprotein cholesterol (HDL-c) (OR = 0.78; 95% CI: 0.66, 0.91). Also, a nonlinear association between serum vitamin D and odds of abnormal lipid profile was found: elevating values of 25-hydroxyvitamin D from 35 nmol/L to 55 nmol/L was associated with a decreasing trend in odds of hypertriglyceridemia, hyper low-density lipoprotein cholesterolemia, hypercholesterolemia, and hypo HDL-cholesterolemia. However, no significant linear association was observed. Based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE), the certainty of all evidence was rated as high.
CONCLUSION
This meta-analysis revealed that the level of 25-hydroxyvitamin D was inversely related to odds of abnormal serum triglycerides and HDL-c in children and adolescents. Increasing serum vitamin D from 35 nmol/L to 55 nmol/L was associated with a decreasing trend in the odds of abnormal serum triglycerides, HDL-c, low-density lipoprotein cholesterol, and total cholesterol in children.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration no. 42023400787.
PubMed: 38568958
DOI: 10.1093/nutrit/nuae020 -
BioMed Research International 2024[This retracts the article DOI: 10.1155/2021/8032978.].
[This retracts the article DOI: 10.1155/2021/8032978.].
PubMed: 38550106
DOI: 10.1155/2024/9865038 -
Endocrine Mar 2024Familial hypercholesterolemia (FH) is one of the most common inherited diseases characterized by elevated LDL-cholesterol levels, leading to early-onset atherosclerosis.... (Review)
Review
PURPOSE
Familial hypercholesterolemia (FH) is one of the most common inherited diseases characterized by elevated LDL-cholesterol levels, leading to early-onset atherosclerosis. While the association between FH and coronary and carotid artery disease is well-established, its association with peripheral artery disease (PAD) is less robust. This systematic review aims at exploring existing evidence on PAD prevalence and incidence in FH individuals.
METHODS
A comprehensive search was conducted on MEDLINE and Embase databases, for studies published between January 2013 and December 2023, evaluating prevalence and incidence of PAD in FH patients. Literature reviews, case reports, responses to editors and non-English language articles were excluded.
RESULTS
The initial research provided 53 results. After article screening, 28 articles were fully reviewed and 24 were finally included in the analysis. Among these, 19 reported PAD prevalence, while 5 PAD incidence over a mean follow-up time of 8.7 years. PAD prevalence and incidence ranged from 0.3 to 60% and from 0.5 to 4.2% respectively, probably reflecting the heterogeneity in PAD definition criteria.
CONCLUSION
This systematic review sheds light on the limited number of studies on PAD in FH patients. Particularly, considering the potential positive effects of newly available lipid-lowering strategies on PAD outcomes, addressing this research gap is pivotal for a more comprehensive understanding of peripheral vascular manifestations in FH patients and for optimal management of this population.
PubMed: 38457056
DOI: 10.1007/s12020-024-03763-x -
Critical Pathways in Cardiology Jun 2024To find out whether inclisiran sodium has different efficacy in heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH)... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To find out whether inclisiran sodium has different efficacy in heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH) patient groups.
METHODS
We conducted the systematic review and meta-analysis of ORION clinical trials. PubMed, Embase, and Clinicaltrials.gov databases were searched for the relevant studies. Atheroscalerotic parameters considered for our objective were low-density lipoprotein cholesterol, total cholesterol, proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B, and nonhigh-density lipoprotein cholesterol. Primary outcomes were the percentage difference in atheroscalerotic parameters at follow-up relative to baseline values. Our study examined these primary outcomes to determine whether there is a statistically significant difference between the HeFH and HoFH groups. Risk of bias was assessed by the Cochrane risk of bias tool. Meta-analysis was performed when at least 2 studies reported on the same variable.
RESULTS
Four ORION clinical trials provided the data related to the mean difference in the atheroscalerotic parameters at follow-up relative to baseline, of HeFH and HoFH patient populations, after administration of 300 mg inclisiran subcutaneously. We pooled together these mean differences for each group and applied a statistical test to analyze if the values were significantly different between the groups. The results of our study unveiled the significant difference in pooled mean differences in low-density lipoprotein cholesterol (HeFH: -48.62%; HoFH: -9.12%; P < 0.05), total cholesterol (HeFH: -30.31%; HoFH: -11.50%; P < 0.05), apolipoprotein (HeFH: -39.97%; HoFH: -14.68%; P < 0.05), and nonhigh-density lipoprotein (HeFH: -44.51%; HoFH: -12.22%; P < 0.05) between HeFH and HoFH groups. However, the difference in pooled mean difference in PCSK9 values (HeFH: -68.41%; HoFH: -56.25%; P = 0.2) between HeFH and HoFH groups was statistically insignificant. Studies were of high quality.
CONCLUSIONS
There was a significant difference in the reductions in atherosclerotic lipid parameters in heterozygous and homozygous populations after the administration of inclisiran except for PCSK9 parameter. Further studies are needed to support this conclusion.
Topics: Humans; Hyperlipoproteinemia Type II; Heterozygote; Homozygote; Cholesterol, LDL; Treatment Outcome; Anticholesteremic Agents; RNA, Small Interfering
PubMed: 38446086
DOI: 10.1097/HPC.0000000000000353 -
International Braz J Urol : Official... 2024Statins are one of the most prescribed classes of drugs worldwide to treat hypercholesterolemia and dyslipidemia. By lowering the level of cholesterol, the use of statin... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Statins are one of the most prescribed classes of drugs worldwide to treat hypercholesterolemia and dyslipidemia. By lowering the level of cholesterol, the use of statin could cause a reduction in testosterone levels. The objective was to evaluate whether the continued use of statins in patients with hypercholesterolemia causes a deficiency in testosterone and other sex hormones.
MATERIALS AND METHODS
Systematic Review with Meta-analysis, performed in Embase, Medline and Cochrane databases, until May 2023; PROSPERO CRD42021270424protocol. Selection performed by two independent authors with subsequent conference in stages. Methodology based on PRISMA statement. There were selected comparative studies, prospective cohorts (CP), randomized clinical trials (RCT) and cross-sectional studies (CSS) with comparison of testosterone levels before and after statin administration and between groups. Bias analysis were evaluated with Cochrane Tool, The Newcastle-Ottawa Scale (NOS), and using the Assess the Quality of Cross-sectional studies (AXIS) tool.
RESULTS
There were found on MedLine, Embase and Cochrane, after selected comparative studies, 10CP and 6RCT and 6CSS for the meta-analysis. In the Forrest plot with 6CSS, a correlation between patients with continuous use of statins and a reduction in total testosterone was evidenced with a statistically significant reduction of 55.02ng/dL (95%CI=[39.40,70.64],I²=91%,p<0.00001).In the analysis with 5RCT, a reduction in the mean total testosterone in patients who started continuous statin use was evidenced, with a statistical significance of 13.12ng/dL (95%CI=[1.16,25.08],I²=0%,p=0.03). Furthermore, the analysis of all prospective studies with 15 articles showed a statistically significant reduction in the mean total testosterone of 9.11 ng/dL (95%CI=[0.16,18.06],I²=37%,p=0.04). A reduction in total testosterone has been shown in most studies and in its accumulated analysis after statin use. However, this decrease was not enough to reach levels below normal.
CONCLUSION
Statins use causes a decrease in total testosterone, not enough to cause a drop below the normal range and also determines increase in FSH levels. No differences were found in LH, Estradiol, SHBG and Free Testosterone analysis.
Topics: Humans; Male; Databases, Factual; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Reference Values; Testosterone
PubMed: 38386784
DOI: 10.1590/S1677-5538.IBJU.2023.0578 -
Semergen 2024Monacolin K is the major active component in red yeast rice (RYR) which is structurally identical to lovastatin and has the most powerful effect, in terms of reducing... (Review)
Review
Monacolin K is the major active component in red yeast rice (RYR) which is structurally identical to lovastatin and has the most powerful effect, in terms of reducing blood cholesterol levels. This review aimed to examine the effect and safety of different doses of monacolin K on blood cholesterol levels. PubMed and Cochrane were searched for articles published between 2012 and 2023 for clinical-trials and randomized-controlled-trials. Eligible studies included participants>18-years-old, of any gender and ethnicity. The intervention/exposure of interest was monacolin K. Hypercholesterolemia was considered the outcome of interest defined as the elevated total or low-density-lipoprotein (LDL) cholesterol levels. 12 randomized-controlled-trials were eligible for inclusion in the analysis including 769 participants>18-years-old. 11 out of 12 studies were assessed with high methodological quality and one study with low methodological quality. Monacolin K supplementation varied between 2mg and 10mg per day and the maximum period of supplementation was 12 weeks. All studies indicated a beneficial effect of monacolin supplementation on LDL and total cholesterol levels (p<0.05) regardless the dose and period of supplementation. Also, 3 of the included studies reported adverse side effects after treatment with monacolin K. Low doses of monacolin K equal to 3mg/day exert potential cholesterol-lowering effects although the number of relative studies is limited. Regarding the safety of monacolin K supplementation, findings seem to be more controversial and therefore, it is suggested for all patients treated with monacolin K to be routinely monitored regardless the dose of supplementation.
Topics: Humans; Hypercholesterolemia; Dietary Supplements; Randomized Controlled Trials as Topic; Lovastatin; Anticholesteremic Agents; Cholesterol, LDL; Dose-Response Relationship, Drug; Cholesterol; Biological Products; Dicarboxylic Acids; Fatty Acids
PubMed: 38310834
DOI: 10.1016/j.semerg.2023.102156 -
PloS One 2024Bempedoic acid, an innovative oral medication, has garnered significant interest in recent times due to its potential as a therapeutic intervention for... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Bempedoic acid, an innovative oral medication, has garnered significant interest in recent times due to its potential as a therapeutic intervention for hypercholesterolemia. Nonetheless, the outcomes of the initial investigations might have been more definitive and coherent. Our objective was to perform a quantitative meta-analysis in order to evaluate bempedoic acid's safety and effectiveness.
METHODS
A search was conducted on ClinicalTrials.gov, and PubMed from the time of inception until September 28, 2023. Randomized controlled trials comparing the safety and efficacy of bempedoic acid among patients with statin intolerance and those without were included in our analysis. The trial outcomes were summarized using a random effects model and were provided as mean differences or odds ratios (ORs) with a confidence interval of 95%. Additionally, trial heterogeneity and the possibility of bias were evaluated and investigated.
RESULTS
Bempedoic acid treatment reduced low-density lipoprotein cholesterol levels more than placebo (mean difference -2.97%, 95% CI -5.89% to -0.05%), according to a pooled analysis of 16 eligible trials. The risk of death (OR 1.18, 95% CI 0.70 to 1.98) and muscle-associated occurrences (OR 1.00, 95% CI 0.77 to 1.31) was not impacted by bempedoic acid. In contrast, discontinuation of treatment was more frequently caused by adverse events in the bempedoic acid group (OR 1.13, 95% CI 1.01 to 1.27).
CONCLUSIONS
In patients with statin intolerance as well as those without, bempedoic acid is a safe and efficacious lipid-lowering agent, according to findings from randomized controlled trials.
Topics: Humans; Dicarboxylic Acids; Fatty Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypolipidemic Agents; Randomized Controlled Trials as Topic
PubMed: 38277431
DOI: 10.1371/journal.pone.0297854 -
PharmacoEconomics Apr 2024OBJECTIVE: This study aimed to systematically synthesise the cost-effectiveness of screening strategies to detect heterozygous familial hypercholesterolemia (FH).
BACKGROUND
OBJECTIVE: This study aimed to systematically synthesise the cost-effectiveness of screening strategies to detect heterozygous familial hypercholesterolemia (FH).
METHODS
We searched seven databases from inception to 2 February , 2023, for eligible cost-effective analysis (CEA) that evaluated screening strategies for FH versus the standard care for FH detection. Independent reviewers performed the screening, data extraction and quality evaluation. Cost results were adapted to 2022 US dollars (US$) to facilitate comparisons between studies using the same screening strategies. Cost-effectiveness thresholds were based on the original study criteria.
RESULTS
A total of 21 studies evaluating 62 strategies were included in this review, most of the studies (95%) adopted a healthcare perspective in the base case, and majority were set in high-income countries. Strategies analysed included cascade screening (23 strategies), opportunistic screening (13 strategies), systematic screening (11 strategies) and population-wide screening (15 strategies). Most of the strategies relied on genetic diagnosis for case ascertainment. The most common comparator was no screening, but some studies compared the proposed strategy versus current screening strategies or versus the best next alternative. Six studies evaluated screening in children while the remaining were targeted at adults. From a healthcare perspective, cascade screening was cost-effective in 78% of the studies [cost-adapted incremental cost-effectiveness ratios (ICERs) ranged from dominant to 2022 US$ 104,877], opportunistic screening in 85% (ICERs from US$4959 to US$41,705), systematic screening in 80% (ICERs from US$2763 to US$69,969) and population-wide screening in 60% (ICERs from US$1484 to US$223,240). The most common driver of ICER identified in the sensitivity analysis was the long-term cost of lipid-lowering treatment.
CONCLUSIONS
Based on reported willingness to pay thresholds for each setting, most CEA studies concluded that screening for FH compared with no screening was cost-effective, regardless of the screening strategy. Cascade screening resulted in the largest health benefits per person tested.
Topics: Adult; Child; Humans; Cost-Benefit Analysis; Hyperlipoproteinemia Type II; Mass Screening
PubMed: 38265575
DOI: 10.1007/s40273-023-01347-7