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Annals of Internal Medicine Jul 2015Guidelines recommend statins as first-line therapy for dyslipidemia. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Guidelines recommend statins as first-line therapy for dyslipidemia. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new lipid-lowering approach.
PURPOSE
To assess the efficacy and safety of PCSK9 antibodies in adults with hypercholesterolemia.
DATA SOURCES
MEDLINE, PubMed Central, and Google Scholar; conference proceedings; and the ClinicalTrials.gov registry through 4 April 2015.
STUDY SELECTION
Phase 2 or 3 randomized, controlled trials (RCTs) comparing treatment using PCSK9 antibodies with no anti-PCSK9 therapy in adults with hypercholesterolemia.
DATA EXTRACTION
Two investigators independently extracted data on study characteristics and lipid and clinical outcomes, and rated risk of bias of trials. Prespecified primary end points were all-cause and cardiovascular mortality.
DATA SYNTHESIS
Twenty-four RCTs comprising 10 159 patients were included. Compared with no antibody, treatment with PCSK9 antibodies led to marked reductions in low-density lipoprotein cholesterol levels (mean difference, -47.49% [95% CI, -69.64% to -25.35%]; P < 0.001] and other atherogenic lipid fractions, and it reduced all-cause mortality (odds ratio [OR], 0.45 [CI, 0.23 to 0.86]; P = 0.015; heterogeneity P = 0.63; I2 = 0%) and cardiovascular mortality (OR, 0.50 [CI, 0.23 to 1.10]; P = 0.084; heterogeneity P = 0.78; I2 = 0%). The rate of myocardial infarction was significantly reduced with use of PCSK9 antibodies (OR, 0.49 [CI, 0.26 to 0.93]; P = 0.030; heterogeneity P = 0.45; I2 = 0%), and increases in the serum creatine kinase level were reduced (OR, 0.72 [CI, 0.54 to 0.96]; P = 0.026; heterogeneity P = 0.65; I2 = 0%). Serious adverse events did not increase with administration of PCSK9 antibodies.
LIMITATION
Results were derived from study-level data rather than patient-level data, and clinical outcome data are rare.
CONCLUSION
PCSK9 antibodies seem to be safe and effective for adults with dyslipidemia.
PRIMARY FUNDING SOURCE
CRC 1116 Masterswitches in Myocardial Ischemia, German Research Council DFG.
Topics: Angina, Unstable; Antibodies, Monoclonal; Anticholesteremic Agents; Cardiovascular Diseases; Cause of Death; Cholesterol; Creatine Kinase; Female; Humans; Hypercholesterolemia; Lipoprotein(a); Male; Middle Aged; Myocardial Infarction; Proprotein Convertase 9; Proprotein Convertases; Serine Endopeptidases
PubMed: 25915661
DOI: 10.7326/M14-2957 -
Frontiers in Pharmacology 2022The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are potent LDL-C lowering agents. However, few head-to-head studies evaluated the efficacy on the...
Efficacy and Safety of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors as Adjuvant Treatments for Patients with Hypercholesterolemia Treated with Statin: A Systematic Review and Network Meta-analysis.
The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are potent LDL-C lowering agents. However, few head-to-head studies evaluated the efficacy on the lowering in other atherogenic apolipoproteins and safety of PCSK9 inhibitors at different dosages as an add-on statins therapy in hypercholesterolemia patients. This study is a systematic review and network meta-analysis of randomized control trials to compare the efficacy of lipid reduction and adverse events of PCSK9 inhibitors in statin-treated hypercholesterolemia patients. PubMed, EMBASE, and Cochrane Library databases were searched till April 20, 2021, for randomized controlled trials. Random-effect network meta-analyses were undertaken to compare the differences in the percent reduction in low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein (a) [Lp(a)] levels and the risk of AEs among different PCSK9 inhibitors. A total of 22 articles with 42,786 patients were included. The lipid reductions in LDL-C, ApoB, and Lp(a) with add-on PCSK9 inhibitors vs. placebo in statin-treated patients across all trials were 50-63%, 43-52%, and 23-31%, respectively. Evolocumab 140 mg Q2W was ranked the best among all treatment strategies for lowering LDL-C, ApoB, and Lp(a) levels, and the treatment difference was 68.05% (95% confidence interval (CI), 62.43% to 73.67) in LDL-C reduction, 54.95% (95% CI, 49.55% to 60.35%) in ApoB reduction, and 34.25% (95% CI, 27.59% to 40.91%) in Lp(a) reduction compared with the placebo. No significant risk difference of adverse events between PCSK9 inhibitors and placebo was found. PCSK9 inhibitors showed a significant effect on the reduction in LDL-C, ApoB, and Lp(a) levels in statin-treated patients. Evolocumab 140 mg Q2W showed significantly larger degrees of LDL-C, ApoB, and Lp(a) reduction.
PubMed: 35444537
DOI: 10.3389/fphar.2022.832614 -
The Cochrane Database of Systematic... Jun 2013Hypercholesterolaemia is a significant risk factor for cardiovascular diseases. Isoflavones may be effective in improving hypercholesterolaemia. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hypercholesterolaemia is a significant risk factor for cardiovascular diseases. Isoflavones may be effective in improving hypercholesterolaemia.
OBJECTIVES
To assess the effects of isoflavones for hypercholesterolaemia.
SEARCH METHODS
We searched the following databases: The Cochrane Library (Issue 9, 2012), MEDLINE, EMBASE, Chinese BioMedical Database and China National Knowledge Infrastructure (all to September 2012).
SELECTION CRITERIA
We considered randomized controlled clinical trials in hypercholesterolaemic participants comparing isoflavones versus placebo, or soy isolated protein added with isoflavones versus soy isolated protein alone.
DATA COLLECTION AND ANALYSIS
Two review authors independently abstracted relevant population and intervention characteristics. We resolved any disagreements through discussion, or if required by a third party. We assessed the risk of bias of trials against key criteria: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting and other sources of bias.
MAIN RESULTS
We included five randomized trials (208 participants, 104 in the intervention group and 104 in the control group). Interventions ranged from three to six months. Four trials reported results in non-Asian populations published in English. One trial reported results in Chinese people published in Chinese. Overall, the risk of bias of included trials was high or unclear. There were no outcome data on death from any cause, morbidity, complications, health-related quality of life and costs. Two trials reported adverse effects, including gastrointestinal discomfort (bloating and constipation) and an increased number of hot flushes. None of the trials found serious adverse events. There was a slight significant effect on triglycerides in favour of isoflavones when compared with placebo (mean difference (MD) -0.46 mmol/L (95% confidence interval (CI) -0.84 to -0.09; P = 0.02; 52 participants; 2 trials). No statistically significant effects on total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol were shown in favour of isoflavones.
AUTHORS' CONCLUSIONS
We found no evidence for effects of isoflavones on patient-important outcomes or lowering of cholesterol levels in people with hypercholesterolaemia. Our findings have to be interpreted with caution due to high or unclear risk of bias in several risk of bias domains, and low number of participants in trials.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Hypercholesterolemia; Isoflavones; Middle Aged; Randomized Controlled Trials as Topic; Soybean Proteins
PubMed: 23744562
DOI: 10.1002/14651858.CD009518.pub2 -
Frontiers in Public Health 2017Familial hypercholesterolemia (FH) is an autosomal-dominant hereditary disorder of lipid metabolism that causes lifelong exposure to increased LDL levels resulting in...
BACKGROUND
Familial hypercholesterolemia (FH) is an autosomal-dominant hereditary disorder of lipid metabolism that causes lifelong exposure to increased LDL levels resulting in premature coronary heart disease and, if untreated, death. Recent studies have shown its prevalence to be higher than previously considered, which has important implications for the mortality and morbidity of associated cardiovascular disease (CVD). Several clinical tools are used worldwide to help physicians diagnose FH, but nevertheless most patients remain undetected. This systematic review of guidelines aims to assess the role of genetic testing in the screening, diagnosis, and management of patients affected by heterozygous or homozygous FH and to identify related health-care pathways.
METHODS
We performed a systematic review of the literature; inclusion criteria were English or Italian guidelines focusing on genetic testing. The guidelines were included and evaluated for their content and development process using the Appraisal of Guidelines for Research and Evaluation II instrument.
RESULTS
Ten guidelines were considered eligible, and all were judged to be of good quality, with slight differences among them. The most common indications for performing genetic tests were high levels of cholesterol, or physical findings consistent with lipid disorder, in the subject or in the family history. Subsequent screening of family members was indicated when a mutation had been identified in the index patient. Regarding patient management, the various guidelines agreed that intensive treatment with lipid-lowering medications should begin as quickly as possible and that lifestyle modifications should be an integral part of the therapy.
CONCLUSION
Since the early detection of affected patients is beneficial for effective prevention of CVD, genetic testing is particularly useful for identifying family members cascade screening and for distinguishing between heterozygous and homozygous individuals, the latter of which require more extreme therapeutic intervention.
PubMed: 28993804
DOI: 10.3389/fpubh.2017.00252 -
Medicina (Kaunas, Lithuania) Nov 2023: Lipid-lowering agents such as ezetimibe are recommended in uncontrolled hyperlipidemia for primary and secondary prevention of cardiovascular disease. Carotid... (Meta-Analysis)
Meta-Analysis
Effect of Combination Therapy with Ezetimibe and Statins versus Statin Monotherapy on Carotid Intima-Media Thickness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
: Lipid-lowering agents such as ezetimibe are recommended in uncontrolled hyperlipidemia for primary and secondary prevention of cardiovascular disease. Carotid intima-media thickness (CIMT) is a surrogate marker of atherosclerosis and a predictor of cardiovascular and cerebral events. The effects of ezetimibe on CIMT have been inconsistently reported. The aim of this meta-analysis is to compare the effects of ezetimibe/statin and statin alone therapies on CIMT reduction. : The PubMed, Embase, and Cochrane library databases were searched for randomized controlled trials (RCTs) published prior to 26 January 2023 with the MeSH keywords 'Ezetimibe' and 'Carotid Intima-Media Thickness'. The results were presented as standard mean difference (SMD) with 95% confidence intervals using the random-effect model method, and heterogeneity was assessed. Subgroup, meta-regression, and sensitivity analyses were conducted. : Five RCTs with 642 participants were included. CIMT reduction was not significantly different between the ezetimibe/statin and statin alone groups. However, in subgroup analyses, CIMT in the ezetimibe/statin group was significantly reduced in patients with non-familial hypercholesterolemia (SMD: -0.34 mm and = 0.002) and in patients with secondary prevention (SMD: -0.38 mm and = 0.002). The low-density lipoprotein cholesterol level was significantly reduced in the ezetimibe/statin group (SMD: -0.58 mg/dL and < 0.001). : The effect of ezetimibe on CIMT reduction was shown in non-familial hypercholesterolemia and secondary prevention. These results suggest that the efficacy of ezetimibe may vary with potential CIMT reduction benefits in certain subpopulations.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ezetimibe; Carotid Intima-Media Thickness; Hypercholesterolemia; Anticholesteremic Agents; Azetidines; Cholesterol, LDL; Randomized Controlled Trials as Topic; Drug Therapy, Combination
PubMed: 38004029
DOI: 10.3390/medicina59111980 -
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 -
Frontiers in Cardiovascular Medicine 2023Researchers have conducted a considerable number of epidemiological studies on dyslipidemia in China over recent years. Nevertheless, a representative study to... (Review)
Review
BACKGROUND
Researchers have conducted a considerable number of epidemiological studies on dyslipidemia in China over recent years. Nevertheless, a representative study to comprehensively appraise for the epidemiological status of dyslipidemia is still lacked. This meta-analysis is intended to explore the pooled prevalence, rates of awareness, treatment, and control of dyslipidemia among adults in Chinese Mainland.
MATERIALS AND METHODS
A systematic review was performed on relevant cross-sectional studies published since January 2012 by searching six authoritative literature databases. Meta-analyses were conducted in included studies based on a random-effect model to summarize the epidemiological status of dyslipidemia in China. A potential source of heterogeneity was detected by subgroup analysis and meta-regression. Publication bias was assessed by 's test and funnel plots. A sensitivity analysis was conducted to examine the study quality's influence on the pooled estimate of prevalence and rates of awareness, treatment, and control.
RESULTS
Forty-one original researches with a total of 1,310,402 Chinese participants were finally included in the meta-analysis. The prevalence, rates of awareness, treatment, and control of dyslipidemia were 42.1%, 18.2%, 11.6%, and 5.4%, respectively. With a pooled prevalence estimate at 24.5%, low HDL-C was the most prevalent among various dyslipidemia types, followed by hypertriglyceridemia (TG) (15.4%), hypercholesterolemia (TC) (8.3%), and high LDL-C (7.1%). The pooled prevalence of elevated serum lipoprotein(a) [Lp(a)] was 19.4%. By gender, the prevalence of dyslipidemia was 47.3% in males and 38.8% in females. Subgroup analyses revealed that the prevalence in southern and urban areas were higher than their counterparts. Females and population in urban areas tended to possess higher rates of awareness, treatment, and control. Meta-regression analyses suggested that the year of screening influenced prevalence estimates for dyslipidemia. The impact of the study's quality on the pooled estimates is insignificant.
CONCLUSION
Our study suggested a severe epidemic situation of dyslipidemia among adults in Chinese Mainland. More importantly, the awareness, treatment, and control rates were extremely low, revealing that dyslipidemia is a grave health issue. Consequently, we should attach more importance to the management of dyslipidemia, especially in economically underdeveloped areas.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO [CRD42022366456].
PubMed: 37476570
DOI: 10.3389/fcvm.2023.1186330 -
Clinical Drug Investigation May 2023Janus kinase (JAK) inhibitors are emerging as a therapeutic option for alopecia areata. The risk of potential adverse events is currently debated. In particular, several...
BACKGROUND AND OBJECTIVES
Janus kinase (JAK) inhibitors are emerging as a therapeutic option for alopecia areata. The risk of potential adverse events is currently debated. In particular, several safety data for JAK inhibitors are extrapolated from a single study in elderly patients with rheumatoid arthritis treated with tofacitinib or adalimumab/etanercept as a comparator. The population of patients with alopecia areata is clinically and immunologically different from persons with rheumatoid arthritis and tumor necrosis factor (TNF) inhibitors are not effective in these patients. The objective of this systematic review was to analyze available data on the safety of various JAK inhibitors in patients with alopecia areata.
METHODS
The systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature review was performed by searching PubMed, Scopus and EBSCO databases with the last search on March 13, 2023.
RESULTS
In total, 36 studies were included. The frequency and odds ratio (OR) for most common adverse events versus placebo were: for baricitinib hypercholesterolemia (18.2% vs 10.5%, OR = 1.9) and headache (6.1% vs 5.1%, OR = 1.2), for brepocitinib elevated creatinine level (27.7% vs 4.3%, OR = 8.6) and acne (10.6% vs 4.3%, OR = 2.7), for ritlecitinib acne (10.4% vs 4.3%, OR = 2.6) and headache (12.5% vs 10.6%, OR = 1.2) and for deuruxolitinib headache (21.4% vs 9.1%, OR = 2.7) and acne (13.6% vs 4.5%, OR = 3.3). The respective numbers for upper respiratory infections were: baricitinib (7.3% vs 7.0%, OR = 1.0) and brepocitinib (23.4% vs 10.6%, OR = 2.6); for nasopharyngitis: ritlecitinib (12.5% vs 12.8%, OR = 1.0) and deuruxolitinib (14.6% vs 2.3%, OR = 7.3).
CONCLUSIONS
The most common side effects of JAK inhibitors in patients with alopecia areata were headache and acne. The OR for upper respiratory tract infections varied from over 7-fold increased to comparable to placebo. The risk of serious adverse events was not increased.
Topics: Humans; Aged; Janus Kinase Inhibitors; Alopecia Areata; Protein Kinase Inhibitors; Arthritis, Rheumatoid; Alopecia
PubMed: 37138134
DOI: 10.1007/s40261-023-01260-z -
The Cochrane Database of Systematic... Sep 2016There are approximately 24 million people worldwide with dementia; this is likely to increase to 81 million by 2040. Dementia is a progressive condition, and usually... (Review)
Review
BACKGROUND
There are approximately 24 million people worldwide with dementia; this is likely to increase to 81 million by 2040. Dementia is a progressive condition, and usually leads to death eight to ten years after first symptoms. End-of-life care should emphasise treatments that optimise quality of life and physicians should minimise unnecessary or non-beneficial interventions. Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors; they have become the cornerstone of pharmacotherapy for the management of hypercholesterolaemia but their ability to provide benefit is unclear in the last weeks or months of life. Withdrawal of statins may improve quality of life in people with advanced dementia, as they will not be subjected to unnecessary polypharmacy or side effects. However, they may help to prevent further vascular events in people of advanced age who are at high risk of such events.
OBJECTIVES
To evaluate the effects of withdrawal or continuation of statins in people with dementia on: cognitive outcomes, adverse events, behavioural and functional outcomes, mortality, quality of life, vascular morbidity, and healthcare costs.
SEARCH METHODS
We searched ALOIS (medicine.ox.ac.uk/alois/), the Cochrane Dementia and Cognitive Improvement Group Specialised Register on 11 February 2016. We also ran additional searches in MEDLINE, EMBASE, PsycINFO, CINAHL, Clinical.Trials.gov and the WHO Portal/ICTRP on 11 February 2016, to ensure that the searches were as comprehensive and as up-to-date as possible.
SELECTION CRITERIA
We included all randomised, controlled clinical trials with either a placebo or 'no treatment' control group. We applied no language restrictions.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed whether potentially relevant studies met the inclusion criteria, using standard methodological procedures expected by Cochrane. We found no studies suitable for inclusion therefore analysed no data.
MAIN RESULTS
The search strategy identified 28 unique references, all of which were excluded.
AUTHORS' CONCLUSIONS
We found no evidence to enable us to make an informed decision about statin withdrawal in dementia. Randomised controlled studies need to be conducted to assess cognitive and other effects of statins in participants with dementia, especially when the disease is advanced.
PubMed: 27610945
DOI: 10.1002/14651858.CD012050.pub2 -
Journal of Clinical Medicine Jan 2023Cardiovascular diseases are the leading cause of death globally. There are six cardiovascular risk factors: diabetes, hypertension, hypercholesterolemia, overweight,... (Review)
Review
BACKGROUND
Cardiovascular diseases are the leading cause of death globally. There are six cardiovascular risk factors: diabetes, hypertension, hypercholesterolemia, overweight, sedentary lifestyle and smoking. Due to the low attendance of healthy people in the health system, the use of telemedicine can influence the acquisition of a heart-healthy lifestyle.
OBJECTIVE
this systematic review and meta-analysis aimed to determine the effectiveness of telemedicine and e-health in reducing cardiovascular risk.
METHODS
A systematic review and meta-analysis were carried out using the PubMed, Scopus, Cinhal and WOS databases. Randomized controlled studies between 2017 and 2022 in which telemedicine was used to reduce any of the risk factors were included. The methodological quality was assessed using the "PEDro" scale.
RESULTS
In total, 763 studies were obtained; after the review, 28 target articles were selected and finally grouped as follows: 13 studies on diabetes, six on hypertension, seven on obesity and two on physical activity. For all of the risk factors, a small effect of the intervention was seen.
CONCLUSIONS
although the current evidence is heterogeneous regarding the statistically significant effects of telemedicine on various cardiovascular risk factors, its clinical relevance is undeniable; therefore, its use is recommended as long as the necessary infrastructure exists.
PubMed: 36769487
DOI: 10.3390/jcm12030841