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Expert Review of Clinical Pharmacology May 2022Statins might prevent cell adhesion to the endothelium, a key step in atherosclerosis. We conducted a systematic review and meta-analysis of the effect of statins on... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Statins might prevent cell adhesion to the endothelium, a key step in atherosclerosis. We conducted a systematic review and meta-analysis of the effect of statins on soluble vascular (sVCAM-1) and intercellular (sICAM-1) adhesion molecule 1.
METHODS
A systematic literature search was conducted in PubMed, Web of Science, and Scopus, from inception to July 2021. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist for analytical studies and GRADE, respectively.
RESULTS
Statins significantly reduced both sVCAM-1 (standard mean difference, SMD = -0.28, 95% CI -0.44 to -0.12, p = 0.001; 46 treatment arms; low certainty of evidence) and sICAM-1 (SMD = -0.75, 95% CI -1.00 to -0.50, p < 0.001; 61 treatment arms; moderate certainty of evidence) concentrations. In sensitivity analysis, the SMD values were not modified when individual studies were sequentially removed. There were significant associations between SMD and publication year and, for sICAM-1, statin-induced changes in HDL-cholesterol. In subgroup analysis, the lowering effect was significant with lipophilic, but not hydrophilic, statins, and similar, for sICAM-1, in participants with or without clinically overt atherosclerosis.
CONCLUSIONS
Statins significantly lower sVCAM-1/sICAM-1. Prospective studies are required to determine whether this mediates their atheroprotective effects (PROSPERO registration number: CRD42021276825).
Topics: Atherosclerosis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intercellular Adhesion Molecule-1; Prospective Studies; Vascular Cell Adhesion Molecule-1
PubMed: 35485866
DOI: 10.1080/17512433.2022.2072294 -
Deutsches Arzteblatt International Jul 2016To date, most clinical comparisons of ezetimibe-statin combination therapy versus statin monotherapy have relied entirely on surrogate variables. In this systematic... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
To date, most clinical comparisons of ezetimibe-statin combination therapy versus statin monotherapy have relied entirely on surrogate variables. In this systematic review, we study the efficacy and safety of ezetimibe-statin combination therapy in comparison to statin monotherapy in terms of the prevention of cardiovascular events in hyperlipidemic patients with atherosclerosis and/or diabetes mellitus.
METHODS
This review is based on a systematic literature search (1995 to July 2015) in PubMed, the Excerpta Medica Database (EMBASE), the Cochrane Library, and the ClinicalTrials.gov registry.
RESULTS
Nine randomized, controlled trials with data from a total of 19 461 patients were included. Ezetimibe-statin combination therapy was associated with a lower risk of cardiovascular events than statin monotherapy: 33% of the patients treated with ezetimibe and a statin, and 35% of those treated with a statin alone, had a cardiovascular event within seven years (number needed to treat [NNT]: 50 over 7 years). Combination therapy was also significantly more effective in preventing a composite endpoint consisting of death due to cardiovascular disease, nonfatal myocardial infarction, unstable angina pectoris, coronary revascularization, and nonfatal stroke (hazard ratio [HR] 0.94, 95% confidence interval [0,89; 0,99]; p = 0.016). Diabetic patients benefited from combination therapy rather than monotherapy with respect to cardiovascular morbidity (HR 0.87 [0.78; 0.94]). On the other hand, the addition of ezetimibe to statin therapy did not lessen either cardiovascular or overall mortality. Serious undesired events occurred in 38% of the patients taking ezetimibe and a statin nd in 39% of the patients taking a statin alone (relative risk 1.09 [0.77; 1.55]).
CONCLUSION
In high-risk patients with an acute coronary syndrome, combination therapy with ezetimibe and a statin lowered the risk of cardiovascular events in comparison to statin monotherapy. The risk of dying or suffering an adverse drug effect was similar in the two treatment groups.
Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Anticholesteremic Agents; Causality; Comorbidity; Death, Sudden, Cardiac; Diabetes Mellitus; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; Ezetimibe; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Male; Middle Aged; Risk Factors; Survival Rate; Treatment Outcome
PubMed: 27412989
DOI: 10.3238/arztebl.2016.0445 -
Journal of the American Heart... Feb 2024There is debate over whether statins increase risk of hemorrhagic stroke, so we assessed current evidence, including data from new statin trials and trials of nonstatin... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is debate over whether statins increase risk of hemorrhagic stroke, so we assessed current evidence, including data from new statin trials and trials of nonstatin low-density lipoprotein-cholesterol (LDL-C)- and triglyceride-lowering therapies.
METHODS AND RESULTS
We performed a systematic review of large randomized clinical trials (≥1000 patients with ≥2 years follow-up) of LDL-C-lowering therapy (statin, ezetimibe, and PCSK-9 [proprotein convertase subtilisin/kexin type 9] inhibitor) and triglyceride-lowering therapy (omega-3 supplements and fibrate) that reported hemorrhagic stroke as an outcome. We searched MEDLINE, Embase, and Cochrane Library up to July 2, 2021 and updated a meta-analysis of cardiovascular statin trials published in 2012. Among our several subgroup analyses, we looked at difference depending on stroke status and also depending on age. We identified 37 trials for LDL-C lowering (284 301 participants) and 11 for triglyceride lowering (120 984 participants). Overall, we found a higher risk of hemorrhagic stroke for LDL-C lowering, risk ratio (RR) 1.16 (95% CI, 1.01-1.32, =0.03). For statins (33 trials, 216 258 participants), RR=1.17 (95% CI, 1.01-1.36); for PCSK-9 inhibitors (2 trials, 46 488 participants), RR=0.86 (95% CI, 0.43-1.74); and for ezetimibe (2 trials, 21 555 participants), RR=1.14 (95% CI, 0.64-2.03). In statin trials of patients with previous stroke/transient ischemic attack, RR was 1.46 (95% CI, 1.05-2.04), and in trials with mean age ≥65 years old, RR=1.34 (95% CI, 1.04-1.73) (=0.14 and =0.23 respectively); for triglyceride lowering (11 trials, 120 984 participants), RR=1.05 (95% CI, 0.86-1.30).
CONCLUSIONS
We found evidence for a small increased risk of hemorrhagic stroke events with LDL-C-lowering therapies but no clear evidence for triglyceride-lowering therapies.
REGISTRATION
URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42021275363.
Topics: Humans; Aged; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Anticholesteremic Agents; Cholesterol, LDL; Hemorrhagic Stroke; Cardiovascular Diseases; Randomized Controlled Trials as Topic; Ezetimibe; Stroke; Triglycerides
PubMed: 38323514
DOI: 10.1161/JAHA.123.030714 -
Medicine Jun 2023The prevalence of nonalcoholic fatty liver disease (NAFLD) is rising rapidly in the world. Our aim is to investigate the efficacy and safety of statins in the treatment... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prevalence of nonalcoholic fatty liver disease (NAFLD) is rising rapidly in the world. Our aim is to investigate the efficacy and safety of statins in the treatment of NAFLD.
METHODS
This study was conducted by searching The National Library of Medicine, Cochrane Library, China National Knowledge Infrastructure, Web of Science, and Wanfang Data Knowledge Service Platform databases. Literature data are expressed as mean difference (MD) and 95% confidence intervals (CIs) or relative risk and 95% CI. For I2 > 50% trials, random effect model is used for statistical analysis, otherwise fixed effect model is used.
RESULTS
Fourteen studies are selected for this meta-analysis, which includes totally 534 patients in the treatment group and 527 patients in the control group. As a result, 5 studies show that the total effective rate of the treatment group is 17% higher than that of the control group (Z = 2.11, relative risk = 1.17, 95% CI: [1.01-1.35]). Twelve studies show that alanine aminotransferase levels of the experimental group are lower than that of the control group (Z = 2.63, P = .009, MD = -5.53, 95% CI: [-9.64 to -1.41]). Eleven studies show that aspartate transaminase levels of the experimental group are lower than that of the control group (Z = 2.01, P = .04, MD = -3.43, 95% CI: [-6.77 to -0.08]). Six studies show that alkaline phosphatase levels of the experimental group are lower than that of the control group (Z = 0.79, P = .43, MD = -3.46, 95% CI: [-12.08 to 5.16]). Eight studies show that gamma-glutamyl transpeptidase levels of the experimental group are lower than that of the control group (Z = 2.04, P = .04, MD = -4.05, 95% CI: [-7.96 to -0.15]). Thirteen studies show that triglyceride levels of the experimental group are lower than that of the control group (Z = 4.15, P < .0001, MD = -0.94, 95% CI: [-1.39 to -0.50]). Eleven studies show that the total cholesterol levels of the experimental group are lower than that of the control group (Z = 5.42, P < .00001, MD = -1.51, 95% CI: [-2.05 to -0.96]). Seven studies show that low-density lipoprotein-cholesterol levels of the experimental group are lower than that of the control group (Z = 5.00, P < .00001, MD = -0.85, 95% CI: [-1.18 to -0.52]).
CONCLUSION
Statins can significantly reduce liver biochemical indicators in patients with NAFLD.
Topics: United States; Humans; Non-alcoholic Fatty Liver Disease; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Control Groups; Cholesterol
PubMed: 37390233
DOI: 10.1097/MD.0000000000033981 -
Mayo Clinic Proceedings Nov 2013To evaluate the effect of statins on short-term cognitive function and the long-term incidence of dementia. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the effect of statins on short-term cognitive function and the long-term incidence of dementia.
PATIENTS AND METHODS
A systematic search was performed of MEDLINE, EMBASE, and the Cochrane Central Register from their inception to April 25, 2013. Adults with no history of cognitive dysfunction treated with statins were included from high-quality randomized controlled trials and prospective cohort studies after formal bias assessment.
RESULTS
Sixteen studies were included in qualitative synthesis and 11 in quantitative synthesis. Short-term trials did not show a consistent effect of statin therapy on cognitive end points. Digit Symbol Substitution Testing (a well-validated measure of cognitive function) was the most common short-term end point, with no significant differences in the mean change from baseline to follow-up between the statin and placebo groups (mean change, 1.65; 95% CI, -0.03 to 3.32; 296 total exposures in 3 trials). Long-term cognition studies included 23,443 patients with a mean exposure duration of 3 to 24.9 years. Three studies found no association between statin use and incident dementia, and 5 found a favorable effect. Pooled results revealed a 29% reduction in incident dementia in statin-treated patients (hazard ratio, 0.71; 95% CI, 0.61-0.82).
CONCLUSION
In patients without baseline cognitive dysfunction, short-term data are most compatible with no adverse effect of statins on cognition, and long-term data may support a beneficial role for statins in the prevention of dementia.
Topics: Adult; Cognition; Cognition Disorders; Dementia; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Treatment Outcome
PubMed: 24095248
DOI: 10.1016/j.mayocp.2013.07.013 -
Journal of Clinical Pharmacy and... Apr 2010Statins are the most commonly prescribed agents for hypercholesterolemia because of their efficacy and tolerability. As the number of patients in need of statin therapy... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Statins are the most commonly prescribed agents for hypercholesterolemia because of their efficacy and tolerability. As the number of patients in need of statin therapy continues to increase, information regarding the relative efficacy and safety of statins is required for decision-making.
OBJECTIVE
This study will use systematic review to compare the efficacy and safety profiles of different statins at different doses and determine the therapeutically equivalent doses of statins to achieve a specific level of low-density lipoprotein cholesterol (LDL-C) lowering effect.
METHODS
Publications of head-to-head randomized controlled trials (RCTs) of statins were retrieved from the Oregon state database (1966-2004), MEDLINE (2005-April of 2006), EMBASE (2005-April of 2006), and the Cochrane Controlled Trials Registry (up to the first quarter of 2006). The publications were evaluated with predetermined criteria by a reviewer before they were included in the review. The mean change in cholesterol level of each statin was calculated and weighted by number of subjects involved in each RCT. Where possible, meta-analysis was performed to generate pooled estimates of the cholesterol lowering effect of statins and the difference between statins.
RESULTS
Seventy-five studies reporting RCTs of head-to-head comparisons on statins were included. Most studies had similar baseline characteristics, except the rosuvastatin related studies. A daily dose of atorvastatin 10 mg, fluvastatin 80 mg, lovastatin 40-80 mg, and simvastatin 20 mg could decrease LDL-C by 30-40%, and fluvastatin 40 mg, lovastatin 10-20 mg, pravastatin 20-40 mg, and simvastatin 10 mg could decrease LDL-C by 20-30%. The only two statins that could reduce LDL-C more than 40% were rosuvastatin and atorvastatin at a daily dose of 20 mg or higher. Meta-analysis indicated a statistically significant but clinically minor difference (<7%) between statins in cholesterol lowering effect. Comparisons of coronary heart disease prevention and safety could not be made because of insufficient data.
CONCLUSIONS
At comparable doses, statins are therapeutically equivalent in reducing LDL-C.
Topics: Anticholesteremic Agents; Cholesterol, LDL; Dose-Response Relationship, Drug; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Randomized Controlled Trials as Topic; Therapeutic Equivalency
PubMed: 20456733
DOI: 10.1111/j.1365-2710.2009.01085.x -
Journal of Clinical Laboratory Analysis Jul 2022The incidence of premature atherosclerotic cardiovascular disease in familial hypercholesterolemia (FH) is high. In recent years, novel therapeutic modalities have shown... (Review)
Review
BACKGROUND
The incidence of premature atherosclerotic cardiovascular disease in familial hypercholesterolemia (FH) is high. In recent years, novel therapeutic modalities have shown significant lipid-lowering ability. In this paper, we summarize the recent developments in novel therapies for FH via the treatment of different targets and discuss the characteristics of each targeted therapy. Based on the process of protein synthesis, we attempt to summarize the direct-effect targets including protein, RNA, and DNA.
METHODS
For this systematic review, relevant studies are assessed by searching in several databases including PubMed, Web of Science, Scopus, and Google Scholar. The publications of original researches are considered for screening.
RESULTS
Most drugs are protein-targeted such as molecule-based and monoclonal antibodies, including statins, ezetimibe, alirocumab, evolocumab, and evinacumab. Both antisense oligonucleotide (ASO) and small interfering RNA (siRNA) approaches, such as mipomersen, vupanorsen, inclisiran, and ARO-ANG3, are designed to reduce the number of mRNA transcripts and then degrade proteins. DNA-targeted therapies such as adeno-associated virus or CRISPR-Cas9 modification could be used to deliver or edit genes to address a genetic deficiency and improve the related phenotype.
CONCLUSION
While the therapies based on different targets including protein, RNA, and DNA are on different stages of development, the mechanisms of these novel therapies may provide new ideas for precision medicine.
Topics: Anticholesteremic Agents; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Oligonucleotides, Antisense; RNA
PubMed: 35712827
DOI: 10.1002/jcla.24552 -
Current Reviews in Clinical and... 2023A subpopulation of statin users such as subjects with chronic kidney disease (CKD), Human Immune virus (HIV), acute coronary syndrome (ACS), revascularization, metabolic...
BACKGROUND
A subpopulation of statin users such as subjects with chronic kidney disease (CKD), Human Immune virus (HIV), acute coronary syndrome (ACS), revascularization, metabolic syndrome, and/or diabetes may particularly benefit from pitavastatin pharmacotherapy.
AIM
The current systematic review aimed systematically to evaluate the effect of pitavastatin on primary cardiac events in subjects receiving pitavastatin in comparison to the other four statin members.
METHODS
We conducted a systematic review on phases III and IV of randomized controlled trials (RCT-s, 11 trials) for subjects with primary cardiac events who received pitavastatin. Subjects diagnosed with any type of dyslipidemia (population 4804) and received pitavastatin (interventions) versus comparator (comparison) with the primary efficacy endpoint of minimization of LDL-C and non- HDL-C, had an increase in HDL-C and/or reduction in major adverse cardiac events (MACE, cardiovascular death, myocardial infarction (fatal/nonfatal), and stroke (fatal/nonfatal) and/or their composite (outcomes). The secondary safety endpoint was the development of any adverse effects.
RESULTS
In the included trials (11), participants (4804) were randomized for pitavastatin or its comparators such as atorvastatin, pravastatin, rosuvastatin, simvastatin and followed up for 12 to 52 weeks. In terms of the primary outcome (reduction in LDL-C), pitavastatin 4 mg was superior to pravastatin 40 mg in three trials, while the 2 mg pitavastatin was comparable to atorvastatin 10 mg in four trials and simvastatin 20 and 40 mg in two 2 trials. However, rosuvastatin 2.5 mg was superior to pitavastatin 2 mg in two trials. Pitavastatin increased HDL-C and reduced non-HDL-C in eleven trials. Regarding the safety profile, pitavastatin has proved to be tolerated and safe.
CONCLUSION
The FDA-approved indications for pitavastatin included primary dyslipidemia and mixed dyslipidemia as a supplementary therapy to dietary changes to lower total cholesterol, LDL-C, apolipoprotein B (Apo B), triglycerides (TG), and enhance HDL-C. Pitavastatin might be suitable for subjects with diabetes, ACS (reduced revascularization), metabolic syndrome, CKD, HIV, and subjects with low levels of HDL-C. We highly recommend rational individualization for the selection of statin.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Rosuvastatin Calcium; Pravastatin; Cholesterol, LDL; Metabolic Syndrome; Cholesterol, HDL; Randomized Controlled Trials as Topic; Simvastatin; Dyslipidemias; Cardiovascular Diseases; HIV Infections
PubMed: 35642121
DOI: 10.2174/2772432817666220531115314 -
Expert Opinion on Pharmacotherapy Feb 2018Dyslipidemia is commonly associated with endothelial dysfunction and increased cardiovascular risk. Pitavastatin has been shown to reduce total and low-density... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Dyslipidemia is commonly associated with endothelial dysfunction and increased cardiovascular risk. Pitavastatin has been shown to reduce total and low-density lipoprotein cholesterol, to increase high-density lipoprotein (HDL)-cholesterol and improve HDL function. Furthermore, several trials explored its effects on flow-mediated dilation (FMD), as an index of endothelial function. The authors evaluated the effect of pitavastatin therapy on FMD.
METHODS
The authors performed a systematic review and meta-analysis of all clinical trials exploring the impact of pitavastatin on FMD. The search included PubMed-Medline, Scopus, ISI Web of Knowledge and Google Scholar databases. Quantitative data synthesis was performed using a random-effects model, with weighted mean difference (WMD) and 95% confidence interval (CI) as summary statistics.
RESULTS
Six eligible studies comprising 7 treatment arms were selected for this meta-analysis. Overall, WMD was significant for the effect of pitavastatin on FMD (2.45%, 95% CI: 1.31, 3.60, p < 0.001) and the effect size was robust in the leave-one-out sensitivity analysis.
CONCLUSION
This meta-analysis of all available clinical trials revealed a significant increase of FMD induced by pitavastatin.
Topics: Cardiovascular Diseases; Cholesterol, LDL; Databases, Factual; Dyslipidemias; Endothelium, Vascular; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Quinolines; Risk Factors
PubMed: 29334477
DOI: 10.1080/14656566.2018.1428560 -
Pharmacological Research Jan 2016This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) in order to calculate the effect size of statin therapy in... (Meta-Analysis)
Meta-Analysis Review
This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) in order to calculate the effect size of statin therapy in changing plasma cortisol concentrations. Following a systematic search in Medline, SCOPUS, Web of Science and Google Scholar databases (by up to March 01, 2015), 7 eligible RCTs were selected. Random-effects meta-analysis suggested a significant increase in plasma cortisol concentrations following statin therapy (WMD: 6.34%, 95% CI: 1.80, 10.87, p=0.006). Subgroup analysis confirmed the significance of the effect with lipophilic statins comprising atorvastatin, simvastatin, and lovastatin (WMD: 7.00%, 95% CI: 2.21, 11.79, p=0.004) but not with hydrophilic statins (rosuvastatin and pravastatin) (WMD: 0.60%, 95% CI: -13.46, 14.66, p=0.933). In the meta-regression analysis, changes in plasma cortisol concentrations following statin therapy were found to be independent of treatment duration. Results of this meta-analysis of RCTs suggest a significant elevation in plasma cortisol levels following statin therapy.
Topics: Humans; Hydrocortisone; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic
PubMed: 26546969
DOI: 10.1016/j.phrs.2015.10.013