-
The Cochrane Database of Systematic... Nov 2023Cardiovascular disease is the most frequent cause of death in people with early stages of chronic kidney disease (CKD), and the absolute risk of cardiovascular events is... (Review)
Review
BACKGROUND
Cardiovascular disease is the most frequent cause of death in people with early stages of chronic kidney disease (CKD), and the absolute risk of cardiovascular events is similar to people with coronary artery disease. This is an update of a review first published in 2009 and updated in 2014, which included 50 studies (45,285 participants).
OBJECTIVES
To evaluate the benefits and harms of statins compared with placebo, no treatment, standard care or another statin in adults with CKD not requiring dialysis.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 4 October 2023. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. An updated search will be undertaken every three months.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of statins with placebo, no treatment, standard care, or other statins, on death, cardiovascular events, kidney function, toxicity, and lipid levels in adults with CKD (estimated glomerular filtration rate (eGFR) 90 to 15 mL/min/1.73 m) were included.
DATA COLLECTION AND ANALYSIS
Two or more authors independently extracted data and assessed the study risk of bias. Treatment effects were expressed as mean difference (MD) for continuous outcomes and risk ratios (RR) for dichotomous benefits and harms with 95% confidence intervals (CI). The risk of bias was assessed using the Cochrane risk of bias tool, and the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
We included 63 studies (50,725 randomised participants); of these, 53 studies (42,752 participants) compared statins with placebo or no treatment. The median duration of follow-up was 12 months (range 2 to 64.8 months), the median dosage of statin was equivalent to 20 mg/day of simvastatin, and participants had a median eGFR of 55 mL/min/1.73 m. Ten studies (7973 participants) compared two different statin regimens. We were able to meta-analyse 43 studies (41,273 participants). Most studies had limited reporting and hence exhibited unclear risk of bias in most domains. Compared with placebo or standard of care, statins prevent major cardiovascular events (14 studies, 36,156 participants: RR 0.72, 95% CI 0.66 to 0.79; I = 39%; high certainty evidence), death (13 studies, 34,978 participants: RR 0.83, 95% CI 0.73 to 0.96; I² = 53%; high certainty evidence), cardiovascular death (8 studies, 19,112 participants: RR 0.77, 95% CI 0.69 to 0.87; I² = 0%; high certainty evidence) and myocardial infarction (10 studies, 9475 participants: RR 0.55, 95% CI 0.42 to 0.73; I² = 0%; moderate certainty evidence). There were too few events to determine if statins made a difference in hospitalisation due to heart failure. Statins probably make little or no difference to stroke (7 studies, 9115 participants: RR 0.64, 95% CI 0.37 to 1.08; I² = 39%; moderate certainty evidence) and kidney failure (3 studies, 6704 participants: RR 0.98, 95% CI 0.91 to 1.05; I² = 0%; moderate certainty evidence) in people with CKD not requiring dialysis. Potential harms from statins were limited by a lack of systematic reporting. Statins compared to placebo may have little or no effect on elevated liver enzymes (7 studies, 7991 participants: RR 0.76, 95% CI 0.39 to 1.50; I² = 0%; low certainty evidence), withdrawal due to adverse events (13 studies, 4219 participants: RR 1.16, 95% CI 0.84 to 1.60; I² = 37%; low certainty evidence), and cancer (2 studies, 5581 participants: RR 1.03, 95% CI 0.82 to 1.30; I² = 0%; low certainty evidence). However, few studies reported rhabdomyolysis or elevated creatinine kinase; hence, we are unable to determine the effect due to very low certainty evidence. Statins reduce the risk of death, major cardiovascular events, and myocardial infarction in people with CKD who did not have cardiovascular disease at baseline (primary prevention). There was insufficient data to determine the benefits and harms of the type of statin therapy.
AUTHORS' CONCLUSIONS
Statins reduce death and major cardiovascular events by about 20% and probably make no difference to stroke or kidney failure in people with CKD not requiring dialysis. However, due to limited reporting, the effect of statins on elevated creatinine kinase or rhabdomyolysis is unclear. Statins have an important role in the primary prevention of cardiovascular events and death in people who have CKD and do not require dialysis. Editorial note: This is a living systematic review. We will search for new evidence every three months and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
Topics: Adult; Humans; Creatinine; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Infarction; Renal Dialysis; Renal Insufficiency, Chronic; Rhabdomyolysis; Stroke; Systematic Reviews as Topic
PubMed: 38018702
DOI: 10.1002/14651858.CD007784.pub3 -
Cardiovascular Diabetology Nov 2023Bempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Bempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with hypercholesterolemia.
METHODS
PubMed, Scopus, and Cochrane library databases were searched for randomised controlled trials evaluating the efficacy and/or safety of BA compared with placebo. Trials investigating dosages other than 180 mg/die were excluded. Major adverse cardiovascular events (MACE) were the primary efficacy endpoint. LDL-cholesterol reduction was the primary laboratory endpoint. Pre-specified safety endpoints included muscle-related adverse events, new-onset diabetes, and gout. The protocol was registered on PROSPERO (temporary ID:399,867).
RESULTS
Study search identified 275 deduplicated results. 11 studies, encompassing 18,315 patients (9854 on BA vs 8461 on placebo/no treatment) were included. BA was associated with a reduced risk of MACE (OR 0.86, 95% CI 0.79-0.95), myocardial infarction (OR 0.76, 95% CI 0.64-0.88) and unstable angina (OR 0.69, 95% CI 0.54-0.88) compared to control, over a median follow up of 87 (15-162) weeks. BA was associated with a reduction of LDL-Cholesterol (mean difference [MD]-22.42,95% CI - 24.02% to - 20.82%), total cholesterol (- 16.50%,95% - 19.21% to - 13.79%), Apo-B lipoprotein (- 19.55%, - 22.68% to - 16.42%) and high-sensitivity CRP (- 27.83%, - 31.71% to - 23.96%) at 12 weeks. BA was associated with a higher risk of gout (OR 1.55, 95% CI 1.27-1.90) as compared with placebo. Efficacy on laboratory endpoints was confirmed, with a variable extent, across patients on statin or ezetimibe background therapy.
CONCLUSIONS
The improved cholesterol control achieved with BA translates into a reduced risk of MACE, including myocardial infarction and coronary revascularisation. The drug has a satisfactory safety profile except for an increased risk of gout.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol, LDL; Cholesterol; Myocardial Infarction; Gout; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 38017541
DOI: 10.1186/s12933-023-02022-z -
European Journal of Vascular and... Apr 2024Large abdominal aortic aneurysms (AAAs) present a significant mortality risk. While numerous medical interventions have been proposed, no drugs have convincingly reduced... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Large abdominal aortic aneurysms (AAAs) present a significant mortality risk. While numerous medical interventions have been proposed, no drugs have convincingly reduced AAA progression, rupture rates, or repair risk. This systematic review and meta-analysis aimed to assess the impact of re-purposed drugs or dietary supplements on slowing expansion rates, reducing the risk of rupture, or minimising the risk of repair for individuals with AAA.
METHODS
A systematic search was conducted in five databases. Both observational studies and randomised controlled trials were included. Unpublished data from two screening trials were incorporated. Risk of bias was assessed using the Newcastle-Ottawa scale and revised Cochrane risk of bias tool. Meta-analyses were performed for each identified drug subclass and were stratified by overall risk of bias. Results were reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Of 7 484 screened studies, 39 met the inclusion criteria. No studies on dietary supplements were included. A total of 84 cohorts were derived from the included studies, and twelve distinct drug groups underwent meta-analyses. Two drug groups, metformin and statins, were statistically significant in slowing AAA growth. No low risk of bias studies were included for these two drug groups, and the results had very high heterogeneity (I > 80%). Both groups had a GRADE certainty of very low. Metformin, excluding high risk of bias studies, presented an estimated mean growth difference of AAA diameter between users and non-users of -0.73 mm/year, whilst statins had an overall estimated mean difference of -0.84 mm/year.
CONCLUSION
This systematic review and meta-analysis suggests that metformin and statins may provide some effect in slowing AAA progression. However, no definitive evidence was found for any of the investigated drugs included in this study. Further research is needed to identify effective medical treatments for AAA progression with more robust methodology.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Metformin; Aortic Aneurysm, Abdominal
PubMed: 38013062
DOI: 10.1016/j.ejvs.2023.11.037 -
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 -
Medicina Oral, Patologia Oral Y Cirugia... Jan 2024Chitosan is a cheap, accessible, nontoxic, biocompatible, and biodegradable compound. Also, this polysaccharide possesses antibacterial and anti-inflammatory properties....
BACKGROUND
Chitosan is a cheap, accessible, nontoxic, biocompatible, and biodegradable compound. Also, this polysaccharide possesses antibacterial and anti-inflammatory properties. Consequently, a wide range of chitosan applications in the dentistry field has been explored. This work aimed to conduct a systematic review to address the clinical efficacy of chitosan for the treatment of oral mucositis.
MATERIAL AND METHODS
The design of the included studies were observational studies, randomized clinical trials (RCT), and non-randomized clinical trials (non-RCT), whereas, a series of cases, in vivo, and in vitro studies were excluded. The search was performed in PubMed, Web of Science, Scopus, Dentistry and Oral Sciences Source, and ClinicalTrials. Gray literature was searched at Google Scholar. Relevant data from all included studies were recorded. The risk of bias (using RoB 2) and the quality (using Grading of Recommendations Assessment, Development, and Evaluation, GRADE) assessments were carried out.
RESULTS
From the 8413 records screened, 5 clinical trials fully met the eligibility criteria, which comprised a total of 192 participants suffering oral lesions and pain related to oral mucositis. 100% of the included studies exhibited a high risk of bias. The quality of the studies was between low and very low.
CONCLUSIONS
The results of the included studies suggest that chitosan can diminish pain and improve the healing of ulcers in oral mucositis. However, there is no conclusive evidence of chitosan as a superior treatment for oral mucositis compared with other current therapies.
Topics: Humans; Mouth Mucosa; Chitosan; Stomatitis; Inflammation; Pain
PubMed: 37992146
DOI: 10.4317/medoral.25987 -
Current Problems in Cardiology Feb 2024The management of LDL-C levels is pivotal in the prevention of cardiovascular morbidity, particularly among patients at high risk or those intolerant to statins.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The management of LDL-C levels is pivotal in the prevention of cardiovascular morbidity, particularly among patients at high risk or those intolerant to statins. Bempedoic acid emerges as a novel agent in this therapeutic arena.
OBJECTIVES
This systematic review and meta-analysis endeavor to quantify the effectiveness of Bempedoic acid in attenuating LDL-C levels and explore its impact on cardiovascular morbidity, emphasizing its role as an adjunctive or alternative therapy in statin-intolerant or high-risk patients.
METHODS
A comprehensive search spanning PubMed, Google Scholar, and Cochrane Library databases furnished studies for this review. The inclusion was critiqued based on predefined PICOS parameters, ensuring a robust analytical framework.
RESULTS
Bempedoic acid showcased a significant plunge in LDL-C levels (MD -20.69 %, 95 % CI [-23.20, -18.19]), outperforming placebo and ezetimibe monotherapy. The cardioprotective effect was further echoed with a reduced risk of major adverse cardiac events (MACE) in the Bempedoic acid cohort (RR 0.86, 95 % CI [0.80, 0.94]). However, a dive into the safety profile revealed no substantial augmentation in adverse events, affirming its tolerance and efficacy.
CONCLUSIONS
Bempedoic acid represents a potent therapeutic ally, affirming its capacity to significantly pare down LDL-C levels and curtail cardiovascular events. Its favorable safety profile underscores its suitability, especially among those with statin intolerance or individuals categorized within the high-risk vascular bracket, necessitating a paradigm shift in current lipid management strategies.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol, LDL; Randomized Controlled Trials as Topic; Cardiovascular Diseases
PubMed: 37981266
DOI: 10.1016/j.cpcardiol.2023.102191 -
Revista Medica Del Instituto Mexicano... Oct 2023Atorvastatin has been used in the management of dyslipidemia and little is known about the efficacy and safety of high-dose atorvastatin administration for secondary... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Atorvastatin has been used in the management of dyslipidemia and little is known about the efficacy and safety of high-dose atorvastatin administration for secondary prevention of Major Cardiovascular Events (MACE).
OBJECTIVE
To evaluate the impact of high-dose atorvastatin on secondary prevention of MACE and adverse events.
MATERIAL AND METHODS
A systematic review and meta-analysis of Pubmed, Embase, Bireme and Cochrane Library Plus databases was performed, with a time scope from 1990 to July 2022. Six randomized clinical trials were included with a total of 29,333 patients who were treated with 80 mg, 10 mg or placebo doses of Atorvastatin where the main outcomes evaluated were Major Cardiovascular Events (MACE), mortality and treatment safety.
RESULTS
In the comparative study between the use of Atorvastatin 80 mg and other therapies, a relative risk (RR) of 0.8 (95%CI 0.69-0.92) was found, representing a 20% reduction in risk (RRR) and a number needed to treat (NNT) of 30-55. In the analysis of adverse effects, an RR of 2.37 (95% CI 0.86-6.53) and a number needed to harm (NNH) of 14-19 were observed. The use of 80 mg atorvastatin is associated with similar adverse events at lower doses.
CONCLUSIONS
The use of atorvastatin 80 mg is effective in the secondary prevention of Major Cardiovascular Event (MACE). The drug has adverse events that should be taken into account in secondary prevention.
Topics: Humans; Atorvastatin; Cardiovascular Diseases
PubMed: 37934798
DOI: 10.5281/zenodo.8319748 -
Expert Review of Cardiovascular Therapy 2023Statins are highly used in cardiovascular prevention. Statin intolerance is the most significant cause of decreased adherence, translating into a higher cardiovascular... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Statins are highly used in cardiovascular prevention. Statin intolerance is the most significant cause of decreased adherence, translating into a higher cardiovascular risk. This systematic review aims to estimate the incidence of muscle adverse events in patients with a history of statin intolerance receiving placebo.
METHODS
Database search was performed in CENTRAL, MEDLINE, and EMBASE until March 2023. This systematic review included blinded randomized control trials enrolling patients with a history of statin intolerance who received a placebo. A random-effects meta-analysis was performed. Results were presented in percentages, with 95% confidence intervals (95% CI).
RESULTS
Overall, eight studies with 8095 patients with a history of statin intolerance receiving placebo were included. The muscle adverse events incidence rate was 21.34% (95% CI 13.26-30.63%, 8 studies), and discontinuation due to adverse muscle events was 6.12% (95% CI 1.22-13.70%, 3 studies). The incidence was higher in subcutaneous placebo/sham (41.67%, 1 study) compared to oral placebo studies (22.95%, 6 studies).
CONCLUSION
In patients previously labeled as statin-intolerant, about a fifth of the patients exhibited muscle symptoms when receiving a placebo. This highlights the importance of ruling out non-statin-related symptoms to further optimize statin therapy for cardiovascular risk improvement.
Topics: Humans; Arm; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Muscles
PubMed: 37916684
DOI: 10.1080/14779072.2023.2274502 -
International Journal of Molecular... Oct 2023We conducted a meta-analysis and systematic review to investigate the efficacy of chitosan-containing chewing gums, and to test their inhibitory effects on . The... (Meta-Analysis)
Meta-Analysis Review
We conducted a meta-analysis and systematic review to investigate the efficacy of chitosan-containing chewing gums, and to test their inhibitory effects on . The systematic search was performed in three databases (Cochrane Library, EMBASE, and PubMed) and included English-language randomized-controlled trials to compare the efficacy of chitosan in reducing the number of . To assess the certainty of evidence, the GRADE tool was used. Mean differences were calculated with a 95% confidence interval for one outcome: bacterial counts in CFU/mL. The protocol of the study was registered on PROSPERO, registration number CRD42022365006. Articles were downloaded ( = 6758) from EMBASE ( = 2255), PubMed ( = 1516), and Cochrane ( = 2987). After the selection process, a total of four articles were included in the qualitative synthesis and three in the quantitative synthesis. Our results show that chitosan reduced the number of bacteria. The difference in mean quantity was -4.68 × 10. The interval of the random-effects model was [-2.15 × 10; 1.21 × 10] and the prediction interval was [1.03 × 10; 9.40 × 10]. The I2 value was 98% ( = 0.35), which indicates a high degree of heterogeneity. Chitosan has some antibacterial effects when used as a component of chewing gum, but further studies are needed. It can be a promising antimicrobial agent for prevention.
Topics: Humans; Streptococcus mutans; Saliva; Chitosan; Anti-Infective Agents; Anti-Bacterial Agents; Chewing Gum; Dental Caries
PubMed: 37894948
DOI: 10.3390/ijms242015270 -
Journal of Osteopathic Medicine Mar 2024Cardiovascular disease (CVD) is the leading cause of death in the United States. As such, an unmet need exists in the primary and secondary prevention of adverse...
CONTEXT
Cardiovascular disease (CVD) is the leading cause of death in the United States. As such, an unmet need exists in the primary and secondary prevention of adverse cardiovascular events (CVEs). Specifically, identifying drugs that can reduce the progression of CVD and serious adverse events is much needed. Drugs that work by reducing platelet aggregation, blocking cholesterol formation (3-hydroxy-3-methyl-glutaryl-coenzyme A [HMG-CoA] reductase inhibitors), and/or blocking inflammation pathways (mainly interleukin-1b [IL-1b]) have been linked to preventing adverse CVEs, including acetylsalicylic acid (ASA, aspirin), statins, colchicine, and IL-1 inhibitors (interleukin-1 receptor antagonists). This systematic review aims to provide insight into utilizing these four agents for the primary and/or secondary prevention of CVD.
OBJECTIVES
In this systematic review, we opted to review the efficacy of aspirin, statins, colchicine, and IL-1 inhibitors in the primary and secondary prevention of CVE to provide clinical practitioners with evidence-based practice approaches and determine any unmet needs in their utilization.
METHODS
Between October 1 and 12, 2021, a search was conducted and completed on five databases: PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and Biomedical Reference Collection: Comprehensive. A total of 13 researchers (V.A., A.H., S.B., V.G., D.C., C.C., C.B., C.A., S.K., J.H., A.K., S.F., and S.E.) were involved in the search and screening of the articles. Search terms included "aspirin, statins, colchicine, IL-1 inhibitors, and primary, secondary, myocardial infarction (MI)." Inclusion criteria included clinical study design, English language articles, all genders older than 50 years old, and established patient history of CVD, including MI. In addition, articles were excluded if they were animal models, studies, pharmacokinetic studies, systematic reviews, literature reviews, and studies exploring therapies other than those listed in the inclusion criteria. First, five individuals independently sorted through abstracts or articles based on the inclusion and exclusion criteria. Then, a team of 13 individuals sorted through full-text articles of selected abstracts based on the same criteria. A separate researcher resolved conflicts between the team.
RESULTS
A total of 725 articles were identified from all databases, from which 256 duplicated articles were removed. Thus, a total of 469 articles abstracts were screened, of which 425 articles either did not meet the inclusion criteria or met the exclusion criteria. A total of 42 articles were retrieved and assessed for full-text review, from which 15 articles were retrieved for analysis.
CONCLUSIONS
Statins may prevent primary CVEs based on their role in preventing cholesterol formation. Aspirin, canakinumab, and colchicine may be helpful in the secondary prevention of CVEs due to their blocking of various steps in the inflammation pathway leading to CVD. Future research should primarily focus on the use of canakinumab and colchicine in preventing CVD due to the limited number of studies on these drugs.
Topics: Female; Humans; Male; United States; Middle Aged; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Aspirin; Colchicine; Myocardial Infarction; Cholesterol; Inflammation; Interleukin-1
PubMed: 37877246
DOI: 10.1515/jom-2023-0082