-
Current Problems in Cardiology Feb 2024Bempedoic acid (BA) has shown significant progress in reducing cholesterol levels and is relatively free from the many side effects encountered with the use of other... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Bempedoic acid (BA) has shown significant progress in reducing cholesterol levels and is relatively free from the many side effects encountered with the use of other hyperlipidemic drugs such as statins. However, its efficacy in patients with statin intolerance is controversial with inconsistent results among studies.
MATERIALS AND METHODS
An electronic literature search was performed using various databases such as Medline, Google Scholar, and the International Registry of Clinical Trials. The primary endpoint was the change in LDL-C levels. The secondary endpoints included changes in HDL-C, non-HDL-C, triglycerides (TG), clinical outcomes such as MACE, all-cause mortality (ACM), cardiovascular mortality, myocardial infarction (MI), and additional safety outcomes. The least-square mean (LSM) percent change for assessing changes in lipid parameter levels from the baseline and the risk ratio (RR) were used for the evaluation of binary endpoints, with statistical significance set at p<0.05. Random-effects meta-analyses were performed for all the outcomes.
RESULTS
Our analysis included 5 randomized controlled trials (RCTs) with a total of 18,848 participants. BA showed a significant reduction in LDL-C [LSM difference in %: -25.24; 95 % CI: -30.79 to -19.69; p < 0.00001], total cholesterol [LSM difference in %:-21.28; 95 % CI:-30.58 to-11.98; p < 0.00001], non-HDL-C [LSM difference in %: -23.27; 95 % Cl: -29.80 to -16.73 p < 0.00001], and HDL-C [LSM difference in %:-3.37, 95 % CI:-3.73 to-3.01, p < 0.00001] compared to placebo. In terms of clinical efficacy, BA was associated with a lower risk of coronary revascularization [RR:0.81; 95 % CI:0.66 to 0.99; p = 0.04], hospitalization for unstable angina [RR:0.67; 95 % CI:0.50 to 0.88; p = 0.005], and myocardial infarction [RR:0.76; 95 % CI:0.66 to 0.88;p = 0.0004]. No significant difference was observed in MACE [RR:0.81; p = 0.15], ACM [RR:0.86; p = 0.46], cardiovascular-related mortality [RR:0.79; p = 0.44], and stroke [RR:0.83; p = 0.08] between the two groups. In terms of safety efficacy, the risk for myalgia was significantly lower in BA-treated patients than in placebo [RR:0.80; p = 0.0002], while the risk for gout [RR:1.46; p < 0.0001] and hyperuricemia [RR:1.93; p < 0.00001] was higher for BA than for placebo. The risks for other adverse effects, such as neurocognitive disorder, nasopharyngitis urinary tract infection, upper respiratory infection, muscular disorder, and worsening hyperglycemia/DM were comparable between the two groups.
CONCLUSION
Our analysis demonstrated that BA significantly reduced the levels of LDL-C, total cholesterol, non-HDL-C, HDL-C, ApoB, and hs-CRP compared with the placebo group. Additionally, patients who received BA had a lower likelihood of coronary revascularization and hospitalization due to unstable angina, MI, and myalgia. Further large-scale RCTs are required to generate more robust evidence.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol, LDL; Myalgia; Randomized Controlled Trials as Topic; Myocardial Infarction; Angina, Unstable
PubMed: 38043880
DOI: 10.1016/j.cpcardiol.2023.102236 -
Current Developments in Nutrition Dec 2023Atherosclerosis is a key risk factor for developing cardiovascular diseases (CVDs). Flow-mediated dilation (FMD), which reflects vascular reactivity, as well as pulse... (Review)
Review
A Systematic Review of the Impact of Fat Quantity and Fatty Acid Composition on Postprandial Vascular Function in Healthy Adults and Patients at Risk of Cardiovascular Disease.
Atherosclerosis is a key risk factor for developing cardiovascular diseases (CVDs). Flow-mediated dilation (FMD), which reflects vascular reactivity, as well as pulse wave velocity (PWV) and augmentation index (AIx), both markers of arterial stiffness, have emerged as noninvasive, subclinical atherosclerotic markers for the early stages of altered vascular function. In addition to the long-term effects of diet, postprandial processes have been identified as important determinants of CVD risk, and evidence suggests an acute effect of fat quantity and fatty acid (FA) composition on vascular function. However, robust analyses of this association are lacking, especially concerning parameters of arterial stiffness. Therefore, we carried out a systematic literature search in PubMed, Scopus, and the Cochrane Library to investigate the impact of fat quantity and FA composition of meals on postprandial vascular function. Postprandial studies measuring FMD, PWV, and/or AIx in healthy adults and subjects with increased CVD risk (e.g., those with hypercholesterolemia or metabolic syndrome) were analyzed. In total, 24 articles were included; 9 studies focused on the effect of high-fat meals compared with control; and 15 studies investigated the effects of different fat sources. We found that consumption of a high-fat meal causes a reduction in FMD (decrease in vasodilation) and AIx (decrease in arterial stiffness). For eicosapentaenoic acid/docosahexaenoic acid (from fish oil), postprandial assessment (FMD and AIx) indicates a beneficial effect on vascular function. There is limited evidence of an influence of CVD risk on the vascular response to meals with varying fat doses or FA composition. However, meaningful conclusions were difficult to draw because of the large heterogeneity of the studies. Inconsistent results regarding both the impact of fat dose and FA composition on postprandial vascular function should be noted. We propose standardized methods for postprandial protocols to improve data quality in future studies. This review was registered in PROSPERO as CRD42022352986.
PubMed: 38076399
DOI: 10.1016/j.cdnut.2023.102025 -
Frontiers in Cardiovascular Medicine 2024Cardiovascular disease (CVD) is a prevalent non-communicable disease globally and holds the position of being the primary cause of mortality worldwide. Consequently,...
BACKGROUND
Cardiovascular disease (CVD) is a prevalent non-communicable disease globally and holds the position of being the primary cause of mortality worldwide. Consequently, considerable focus has been directed towards the prevention and management of CVD. PCSK9, a frequently targeted element in the treatment and prevention of CVD, can reduce cardiovascular risk by effectively lowering lipid levels even in the context of statin therapy. It also exhibits substantial potential in the diagnosis and treatment of familial hypercholesterolemia from genetic aspects. This bibliometric study aims to analyze and visualize the global trends and emerging hotspots of PCSK9 and CVD researches and provide researchers with new perspectives in further studies.
METHODS
The data was obtained from the Web of Science Core Collection database. A total of 2,474 publications related to PCSK9 and CVD published between January 2006 and July 2023 were included. The VOSviewer was used to analyze most-cited references, co-authorship, co-citation, co-occurrence and generate a collaborative network map of authors, countries, and institutions. CiteSpace was used to analyze author and institution centroids, keyword bursts, and timeline graphs.
RESULT
A total of 2,474 articles related to CVD and PCSK9 were included. The number of articles and citations show an increasing trend from year to year. Publications were mainly from the United States. The most active institution was Amgen Inc. Watts, Gerald F. was the most prolific author. Atherosclerosis was the most published journal. Literature co-citation and keyword co-occurrence revealed that early studies focused on the lipid-lowering effects of PCSK9 inhibitors in the context of statins therapy, long-term efficacy, adverse effects, LDLR, diagnosis and treatment of familial hypercholesterolemia. In recent years, myocardial ischemic protection, CRISPR-based editing, and new therapeutic strategies for arteriosclerotic cardiovascular disease have gotten wide attention. The protein convertase, inflammation, beta-polyacetate, and inclisiran may be the important future research directions.
CONCLUSION
This study analyses the current status and global trends in the CVD and PCSK9 studies comprehensively, which may provide researchers and policymakers with new and comprehensive perspectives on in this field of research.
PubMed: 38887452
DOI: 10.3389/fcvm.2024.1336264 -
Yonsei Medical Journal Jan 2024There are few studies in the literature on the dosage of statin that equivalently reduces low-density lipoprotein cholesterol (LDL-C) compared to an ezetimibe... (Meta-Analysis)
Meta-Analysis
PURPOSE
There are few studies in the literature on the dosage of statin that equivalently reduces low-density lipoprotein cholesterol (LDL-C) compared to an ezetimibe combination and whether such regimens have differences in safety. We compared the lipid-modifying efficacy and safety of 5 mg rosuvastatin/10 mg ezetimibe to those of 20 mg rosuvastatin.
MATERIALS AND METHODS
A literature search was conducted using the PubMed, EMBASE, Cochrane, Web of Sciences, and SCOPUS databases up to December 2021. Human studies investigating the two aforementioned regimens with a randomized controlled design were selected. Outcome variables included the percentage reduction in LDL-C and other lipid parameters and rates of composite adverse events (AEs), including muscle-related symptoms. A random-effects meta-analysis was performed after heterogeneity testing between studies.
RESULTS
Seven studies were included in this meta-analysis. The percentage LDL-C reduction did not differ between the combination and monotherapy groups [standardized mean difference (SMD) 0.08; 95% confidence interval (CI) -0.09 to 0.26; =0.35]. The risk of composite AEs (odds ratio 0.50; 95% CI 0.15 to 1.72; =0.27) of the combination was not different compared to the monotherapy group. The percentage of total cholesterol reduction was greater in the combination group (SMD 0.22; =0.02), whereas that of triglyceride reduction and high-density lipoprotein cholesterol elevation did not differ between the two groups.
CONCLUSION
This meta-analysis showed that 5 mg rosuvastatin/10 mg ezetimibe had largely comparable lipid-modifying efficacy and tolerability as 20 mg rosuvastatin.
Topics: Humans; Rosuvastatin Calcium; Ezetimibe; Cholesterol, LDL; Anticholesteremic Agents; Hypercholesterolemia; Drug Therapy, Combination; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Treatment Outcome
PubMed: 38154476
DOI: 10.3349/ymj.2023.0285 -
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 -
Cureus Dec 2023Cardiovascular diseases (CVDs) represent a major global health concern, responsible for significant morbidity, mortality, and disability. To mitigate the impact of CVDs,... (Review)
Review
Cardiovascular diseases (CVDs) represent a major global health concern, responsible for significant morbidity, mortality, and disability. To mitigate the impact of CVDs, individuals often seek preventive measures, and one such approach is the consumption of green tea. This study aims to provide a comprehensive and up-to-date assessment of the effects of green tea consumption on the prevalence of cardiovascular outcomes. Following PRISMA guidelines, we conducted a systematic review using PubMed and Google Scholar databases to identify relevant studies. Our analysis revealed that the risk factors associated with CVDs can vary across different diseases, with hypertension being a common risk factor for CVD mortality and CVD. Notably, the consumption of green tea exhibited a positive effect on reducing the prevalence of cardiometabolic risks and hypercholesterolemia. Furthermore, green tea consumption was observed to have a beneficial impact on lowering both diastolic and systolic blood pressure. In conclusion, the studies reviewed in this research suggest that the consumption of green tea has a significant and positive influence on cardiovascular health. These findings highlight the potential of green tea as a valuable component of a healthy lifestyle, offering a promising avenue for its use as a dietary supplement to reduce the risk of CVDs.
PubMed: 38161525
DOI: 10.7759/cureus.49775 -
Journal of Clinical Medicine Nov 2023Cardiovascular diseases are the leading cause of death in Spain, according to data from the National Institute of Statistics, with the lack of control of cardiovascular... (Review)
Review
Cardiovascular diseases are the leading cause of death in Spain, according to data from the National Institute of Statistics, with the lack of control of cardiovascular risk factors (CVRF) being the main contributing factor. The CVRFs of greatest clinical interest are high blood pressure (HBP), smoking, diabetes mellitus (DM2), overweight, obesity, hypercholesterolaemia, and sedentary lifestyle. The main objective of this review was to compare the prevalence of the different CVRFs according to population-based studies carried out in Spain. For this, a systematic review based on publications assessing CVRFs in the adult population and estimating their national prevalence was conducted. Pubmed and Dialnet databases were consulted, and the selected articles were analysed using the Critical Appraisal Skills Programme Español (CASPe) tool for cohort studies and the Berra et al. tool for cross-sectional studies. A total of 33 studies were obtained from the autonomous regions of Andalusia, the Canary Islands, Castilla-Leon, Castilla-La Mancha, Catalonia, Extremadura, the Balearic Islands, Madrid, Murcia, and Navarra. In all the population-based studies, there was a greater representation of women in the sample. The most prevalent CVRFs differed across the studies according to the autonomous region targeted, with dyslipidaemia, sedentary lifestyle, high blood pressure, hypercholesterolaemia, overweight, and obesity standing out. Numerous differences exist between the studies included in this review, such as the age range, the CVRFs analysed and their prevalence, and remarkable aspects such as the over-representation of the female sex in all cases. It can be concluded that, based on the presented results, the prevalence of CVRFs in Spain varies according to the autonomous region, the sex of the individual, and the studied age range.
PubMed: 37959409
DOI: 10.3390/jcm12216944 -
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 -
Journal of Clinical Lipidology 2024Diagnosis rate of familial hypercholesterolemia (FH) remained less than 10 % globally and the economic evaluation results of different FH screening strategies varied.... (Review)
Review
AIMS
Diagnosis rate of familial hypercholesterolemia (FH) remained less than 10 % globally and the economic evaluation results of different FH screening strategies varied. This study aimed to systematically review the methodology and results of cost effectiveness analysis (CEA) of FH screening, which will provide evidence support for health-related decision-making.
METHODS
The Medline/PubMed, Embase, Cochrane Library, Web of science, National Health Service Economic Evaluation Database (NHSEED) and CEA Registry databases were electronically searched to collect full economic evaluation from the establishment of the databases to June 30, 2022. The quality of included studies was evaluated by the Consolidated Health Economic Evaluation Reporting Standards statement 2022 (CHEERS 2022) checklist.
RESULTS
Among 232 retrieved studies, 18 economic evaluations were included and all of them are from developed countries, with an average quality score of 0.73. The decision tree model and/or Markov model were constructed by thirteen articles (72 %). Twelve studies (67 %) adopted the healthcare perspective and the lifetime horizon to compare the costs and health outcome of different screening strategies. The results of eight studies indicated that cascade screening was a cost-effective strategy compared with no screening, which was more pronounced in younger adults. Universal screening in young adults aged 16 years or 18-40 years (n=3) and in children aged 1-2 years combined with reverse cascade screening (n=3) are both cost-effective. The probability of being cost-effective for cascade screening (n=6) and universal screening (n=1) of young aged 18-40 years were greater than 95 %.
CONCLUSIONS
Our review demonstrated the economic advantages of cascade screening, universal screening of young adults, and universal screening of newborns combined with reverse cascade screening. Further health economic evaluation is needed in children and in low- and middle-income countries.
Topics: Child; Young Adult; Humans; Infant, Newborn; Cost-Effectiveness Analysis; State Medicine; Hyperlipoproteinemia Type II; Cost-Benefit Analysis; Models, Economic
PubMed: 37980172
DOI: 10.1016/j.jacl.2023.11.001 -
American Journal of Cardiovascular... May 2024Cardiovascular disease remains a significant global health concern, with high low-density lipoprotein cholesterol (LDL-C) levels contributing to an increased risk....
Evaluating the Effectiveness and Safety of Evinacumab in Treating Hypercholesterolemia and Hypertriglyceridemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
BACKGROUND
Cardiovascular disease remains a significant global health concern, with high low-density lipoprotein cholesterol (LDL-C) levels contributing to an increased risk. Familial hypercholesterolemia (FH) further complicates its management, necessitating additional lipid-lowering therapies. Evinacumab, an angiopoietin-like protein 3 monoclonal antibody, has emerged as a potential treatment, particularly for patients with FH, by effectively reducing LDL-C and triglyceride levels. This meta-analysis aimed to evaluate the efficacy and safety of evinacumab across diverse patient populations.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, relevant randomized controlled trials (RCTs) were systematically retrieved from multiple databases until November 24, 2023. The inclusion criteria were studies comparing evinacumab (at doses of 5 and 15 mg) to placebo, with outcomes focusing on lipid levels and adverse events. Standardized protocols were employed for data extraction and quality assessment, and statistical analysis was conducted using RevMan software.
RESULTS
Four RCTs, involving 270 patients, were included in the analysis. The analysis revealed significant reductions in lipid markers, particularly with the 15-mg dose of evinacumab, including triacylglycerols (standard mean difference [SMD] = -6.09, 95% confidence interval [CI] - 14.53 to 2.36, P = 0.16), total cholesterol (SMD = - 6.20, 95% CI - 11.53 to - 0.88, P = 0.02), high-density lipoprotein cholesterol (SMD = - 0.79, 95% CI - 1.27 to - 0.31, P = 0.001), LDL-C (SMD = - 4.58, 95% CI - 9.13 to - 0.03, P = 0.05), apolipoprotein (Apo) B (SMD = - 4.01, 95% CI - 7.53 to - 0.46, P = 0.03), and Apo C3 (SMD = - 7.67, 95% CI - 12.94 to - 2.41, P = 0.004). Adverse event analysis revealed no significant association, indicating good tolerability.
CONCLUSION
High-dose evinacumab (15 mg) consistently demonstrated efficacy in reducing cholesterol and other lipid markers, with favorable tolerability. Further research is warranted to comprehensively assess its safety and clinical effectiveness, emphasizing the need for additional data to support its use in managing cardiovascular disease.
PubMed: 38713309
DOI: 10.1007/s40256-024-00649-1