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Pulmonary Circulation Sep 2016Statins improve pulmonary vascular remodeling and right ventricular hypertrophy in animal models of pulmonary arterial hypertension (PAH). However, clinical trials...
Statins improve pulmonary vascular remodeling and right ventricular hypertrophy in animal models of pulmonary arterial hypertension (PAH). However, clinical trials assessing the efficacy of statins in patients with PAH have reported mixed results. In this systematic review and meta-analysis, we assess the efficacy of statins in patients with PAH. We included randomized controlled clinical trials (RCTs) that evaluated the efficacy of statins in patients with PAH. Primary outcomes were mortality and change in 6-minute walk distance (6MWD). Data are presented as odds ratio (OR) and weighted mean difference (WMD), with 95% confidence intervals (CIs), for binary and continuous variables, respectively. We included 4 RCTs of high quality. The mean age of participants was 42 ± 13 years, and 70% were women. The statins used were simvastatin at 40-80 mg in two trials, atorvastatin 10 mg in one trial, and rosuvastatin 10 mg in the other. In the pooled-data analysis, there was no statistically significant improvement in mortality (OR: 0.75 [95% CI: 0.32-1.74]), 6MWD (WMD: -9.27 [95% CI: -27.73 to 9.20]), or cardiac index (WMD: 0.11 [95% CI: -0.04 to 0.27]) with statin therapy when compared to placebo. There was no difference in adverse events leading to withdrawal of therapy between statin and placebo groups. These data suggest that statins are not beneficial in the treatment of PAH. There is a need for large, well-conducted clinical trials assessing the effects of statins in patients with PAH. Future trials should include homogeneous patient populations and should be long-term, event-driven trials with combined morbidity and mortality end points.
PubMed: 27683606
DOI: 10.1086/687304 -
Health Technology Assessment... Dec 2015Various lipid measurements in monitoring/screening programmes can be used, alone or in cardiovascular risk scores, to guide treatment for prevention of cardiovascular... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Various lipid measurements in monitoring/screening programmes can be used, alone or in cardiovascular risk scores, to guide treatment for prevention of cardiovascular disease (CVD). Because some changes in lipids are due to variability rather than true change, the value of lipid-monitoring strategies needs evaluation.
OBJECTIVE
To determine clinical value and cost-effectiveness of different monitoring intervals and different lipid measures for primary and secondary prevention of CVD.
DATA SOURCES
We searched databases and clinical trials registers from 2007 (including the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the Clinical Trials Register, the Current Controlled Trials register, and the Cumulative Index to Nursing and Allied Health Literature) to update and extend previous systematic reviews. Patient-level data from the Clinical Practice Research Datalink and St Luke's Hospital, Japan, were used in statistical modelling. Utilities and health-care costs were drawn from the literature.
METHODS
In two meta-analyses, we used prospective studies to examine associations of lipids with CVD and mortality, and randomised controlled trials to estimate lipid-lowering effects of atorvastatin doses. Patient-level data were used to estimate progression and variability of lipid measurements over time, and hence to model lipid-monitoring strategies. Results are expressed as rates of true-/false-positive and true-/false-negative tests for high lipid or high CVD risk. We estimated incremental costs per quality-adjusted life-year.
RESULTS
A total of 115 publications reported strength of association between different lipid measures and CVD events in 138 data sets. The summary adjusted hazard ratio per standard deviation of total cholesterol (TC) to high-density lipoprotein (HDL) cholesterol ratio was 1.25 (95% confidence interval 1.15 to 1.35) for CVD in a primary prevention population but heterogeneity was high (I(2) = 98%); similar results were observed for non-HDL cholesterol, apolipoprotein B and other ratio measures. Associations were smaller for other single lipid measures. Across 10 trials, low-dose atorvastatin (10 and 20 mg) effects ranged from a TC reduction of 0.92 mmol/l to 2.07 mmol/l, and low-density lipoprotein reduction of between 0.88 mmol/l and 1.86 mmol/l. Effects of 40 mg and 80 mg were reported by one trial each. For primary prevention, over a 3-year period, we estimate annual monitoring would unnecessarily treat 9 per 1000 more men (28 vs. 19 per 1000) and 5 per 1000 more women (17 vs. 12 per 1000) than monitoring every 3 years. However, annual monitoring would also undertreat 9 per 1000 fewer men (7 vs. 16 per 1000) and 4 per 1000 fewer women (7 vs. 11 per 1000) than monitoring at 3-year intervals. For secondary prevention, over a 3-year period, annual monitoring would increase unnecessary treatment changes by 66 per 1000 men and 31 per 1000 women, and decrease undertreatment by 29 per 1000 men and 28 per 1000 men, compared with monitoring every 3 years. In cost-effectiveness, strategies with increased screening/monitoring dominate. Exploratory analyses found that any unknown harms of statins would need utility decrements as large as 0.08 (men) to 0.11 (women) per statin user to reverse this finding in primary prevention.
LIMITATION
Heterogeneity in meta-analyses.
CONCLUSIONS
While acknowledging known and potential unknown harms of statins, we find that more frequent monitoring strategies are cost-effective compared with others. Regular lipid monitoring in those with and without CVD is likely to be beneficial to patients and to the health service. Future research should include trials of the benefits and harms of atorvastatin 40 and 80 mg, large-scale surveillance of statin safety, and investigation of the effect of monitoring on medication adherence.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42013003727.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Cardiovascular Diseases; Cost-Benefit Analysis; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Models, Statistical; Primary Prevention; Quality-Adjusted Life Years; Risk Factors; Technology Assessment, Biomedical
PubMed: 26680162
DOI: 10.3310/hta191000 -
European Cardiology Jul 2019Acute coronary syndrome (ACS) is characterised by increased effector cells and decreased regulatory T-cells (Tregs). Statins have been shown to be clinically beneficial... (Review)
Review
The Effect of Statins on the Functionality of CD4+CD25+FOXP3+ Regulatory T-cells in Acute Coronary Syndrome: A Systematic Review and Meta-analysis of Randomised Controlled Trials in Asian Populations.
Acute coronary syndrome (ACS) is characterised by increased effector cells and decreased regulatory T-cells (Tregs). Statins have been shown to be clinically beneficial in ACS patients. This effect could be mediated via the induction of Tregs in ACS patients. The aim of this systemic review and meta-analysis was to evaluate whether statin therapy enhances the frequency of Tregs determined by CD4+CD25+FOXP3+ in this subset of patients. A comprehensive search of PubMed and Embase was performed. Studies were restricted to randomised controlled trials that quantified CD4+CD25+FOXP3+ cell frequency by flow cytometric analysis before and after statin treatment in adults diagnosed with ACS. A minimum of at least two of the conventional markers to identify Tregs was compulsory. Four randomised controlled trials studies (439 participants) were included, all with low-to-moderate risk of bias. Pooled data showed a significant increase in Treg frequency after statin therapy in ACS patients. A further meta-regression and subgroup analysis also showed a negative dose-related effect, and a statin type-related effect (rosuvastatin versus atorvastatin), respectively. The results confirmed that statins positively alter the frequency of Tregs, which may indicate a potential mechanism of their therapeutic effect. However, there was a risk of information bias due to the markers used to identify Tregs, which was not fully explored, therefore, further randomised controlled trials should utilise markers of Tregs, such as the FOXP3 locus (Treg-specific demethylated region), for identification.
PubMed: 31360235
DOI: 10.15420/ecr.2019.9.2 -
Journal of Geriatric Psychiatry and... Jul 2022Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most prevalent cause of dementia. In spite of the urgent need for more effective AD drug therapy...
IMPORTANCE
Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most prevalent cause of dementia. In spite of the urgent need for more effective AD drug therapy strategies, evidence of the efficacy of combination therapy with existing drugs remains unclear.
OBJECTIVE
To assess the efficacy of combined drug therapy on cognition and progress in patients with AD in comparison to single agent drug therapy.
METHODS
The electronic databases MEDLINE and EMBASE were systematically searched to identify relevant publications. Only randomized controlled clinical trials were included, but no limits were applied to language or time published. Data were extracted from May 27th until December 29th, 2020.
RESULTS
Three trials found that a combination of ChEI with additional memantine provides a slight benefit for patients with moderate to severe AD over ChEI monotherapy and placebo. However, a further 4 trials could not replicate this effect. One trial reported benefits of add-on in donepezil-treated patients with moderate AD (using a formula containing Gingko and other antioxidants) compared to donepezil with placebo. A further trial found no significant effect of combining EGb 761® and donepezil in patients with probable AD over donepezil with placebo. Approaches with idalopirdine, atorvastatin or vitamin supplementation in combination with ChEI have not proven effective and have not been retried since. Fluoxetine and ST101 have shown partial benefits in combination with ChEI over ChEI monotherapy and placebo. However, these effects must be replicated by further research.
CONCLUSION
Additional memantine in combination with ChEI might be of slight benefit in patients with moderate to severe AD, but evidence is ambiguous. Longer trials are needed. No major cognitive benefit is missed, if solely appropriate ChEI monotherapy is initiated.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Drug Therapy, Combination; Humans; Indans; Memantine; Piperidines
PubMed: 34476990
DOI: 10.1177/08919887211044746 -
American Journal of Kidney Diseases :... Jan 2017To simultaneously evaluate the relative efficacy of multiple pharmacologic strategies for preventing contrast-induced acute kidney injury (AKI). (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
To simultaneously evaluate the relative efficacy of multiple pharmacologic strategies for preventing contrast-induced acute kidney injury (AKI).
STUDY DESIGN
Systematic review containing a Bayesian network meta-analysis of randomized controlled trials.
SETTING & POPULATION
Participants undergoing diagnostic and/or interventional procedures with contrast media.
SELECTION CRITERIA FOR STUDIES
Randomized controlled trials comparing the active drug treatments with each other or with hydration alone.
INTERVENTION
Any of the following drugs in combination with hydration: N-acetylcysteine (NAC), theophylline (aminophylline), fenoldopam, iloprost, alprostadil, prostaglandin E, statins, statins plus NAC, bicarbonate sodium, bicarbonate sodium plus NAC, ascorbic acid (vitamin C), tocopherol (vitamin E), α-lipoic acid, atrial natriuretic peptide, B-type natriuretic peptide, and carperitide.
OUTCOMES
The occurrence of contrast-induced AKI.
RESULTS
The trial network included 150 trials with 31,631 participants and 4,182 contrast-induced AKI events assessing 12 different interventions. Compared to hydration, ORs (95% credible intervals) for contrast-induced AKI were 0.31 (0.14-0.60) for high-dose statin plus NAC, 0.37 (0.19-0.64) for high-dose statin alone, 0.37 (0.17-0.72) for prostaglandins, 0.48 (0.26-0.82) for theophylline, 0.62 (0.40-0.88) for bicarbonate sodium plus NAC, 0.67 (0.54-0.81) for NAC alone, 0.64 (0.41-0.95) for vitamins and analogues, 0.70 (0.29-1.37) for natriuretic peptides, 0.69 (0.31-1.37) for fenoldopam, 0.78 (0.59-1.01) for bicarbonate sodium, and 0.98 (0.41-2.07) for low-dose statin. High-dose statin plus NAC or high-dose statin alone were likely to be ranked the best or the second best for preventing contrast-induced AKI. The overall results were not materially changed in metaregressions or subgroup and sensitivity analyses.
LIMITATIONS
Patient-level data were unavailable; unable to include some treatment agents; low event rates; imbalanced distribution of participants among treatment strategies.
CONCLUSIONS
High-dose statins plus hydration with or without NAC might be the preferred treatment strategy to prevent contrast-induced AKI in patients undergoing diagnostic and/or interventional procedures requiring contrast media.
Topics: Acute Kidney Injury; Bayes Theorem; Contrast Media; Humans; Network Meta-Analysis; Treatment Outcome
PubMed: 27707552
DOI: 10.1053/j.ajkd.2016.07.033 -
Frontiers in Pharmacology 2023Adverse drug reactions (ADRs) are the main safety concerns of clinically used medications. Accumulating evidence has shown that ADRs can affect men and women...
Adverse drug reactions (ADRs) are the main safety concerns of clinically used medications. Accumulating evidence has shown that ADRs can affect men and women differently, which suggests sex as a biological predictor in the risk of ADRs. This review aims to summarize the current state of knowledge on sex differences in ADRs with the focus on the commonly used psychotropic, cardiovascular, and analgesic medications, and to aid clinical decision making and future mechanistic investigations on this topic. PubMed search was performed with combinations of the following terms: over 1,800 drugs of interests, sex difference (and its related terms), and side effects (and its related terms), which yielded over 400 unique articles. Articles related to psychotropic, cardiovascular, and analgesic medications were included in the subsequent full-text review. Characteristics and the main findings (male-biased, female-biased, or not sex biased ADRs) of each included article were collected, and the results were summarized by drug class and/or individual drug. Twenty-six articles studying sex differences in ADRs of six psychotropic medications, ten cardiovascular medications, and one analgesic medication were included in this review. The main findings of these articles suggested that more than half of the ADRs being evaluated showed sex difference pattern in occurrence rate. For instance, lithium was found to cause more thyroid dysfunction in women, and amisulpride induced prolactin increase was more pronounced in women than in men. Some serious ADRs were also found to exert sex difference pattern, such as clozapine induced neutropenia was more prevalent in women whereas simvastatin/atorvastatin-related abnormal liver functions were more pronounced in men.
PubMed: 37201021
DOI: 10.3389/fphar.2023.1096366 -
The Angle Orthodontist Jul 2020To investigate and synthesize systematically the evidence from animal studies pertaining to the effect of pharmacological agents on tooth movement relapse following...
OBJECTIVES
To investigate and synthesize systematically the evidence from animal studies pertaining to the effect of pharmacological agents on tooth movement relapse following cessation of orthodontic force application.
MATERIALS AND METHODS
An electronic search was conducted in seven online databases (including gray sources) without restrictions until the third week of April 2019, followed by a hand search in the reference lists of eligible articles. Controlled animal studies investigating the effect of pharmacological agents on tooth movement relapse following orthodontic treatment were selected. Relevant data were extracted from eligible studies and the risk of bias assessment was done using SYRCLE's risk of bias tool. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation tool.
RESULTS
The search identified 2354 records, of which 7 studies were deemed eligible for inclusion in the qualitative synthesis, with the majority presenting an unclear risk of bias. Orthodontic relapse was shown to decrease with the administration of pamidronate disodium, atorvastatin, aspirin, and chemically modified tetracycline-3. Inconsistent effects on relapse were observed after the use of simvastatin. The overall quality of retrieved evidence was assessed as low at best.
CONCLUSIONS
The available evidence shows that the investigated pharmacological agents may demonstrate variable effects on tooth movement relapse following cessation of orthodontic force. Additional evidence of higher quality is required to draw definitive conclusions on their effects and to make potential recommendations for clinical application.
Topics: Animals; Dental Care; Health Behavior; Humans; Recurrence; Tooth Movement Techniques
PubMed: 33378496
DOI: 10.2319/092619-613.1 -
Journal of Pharmacy & Bioallied Sciences Jul 2023Class II mandibular furcation defect is a periodontal condition characterized by a cul-de-sac lesion, a definite parallel constituent with only a portion of alveolar...
Class II mandibular furcation defect is a periodontal condition characterized by a cul-de-sac lesion, a definite parallel constituent with only a portion of alveolar bone remaining intact. There may be involvement of vertical bone loss. Local drug deliveries such as Boric acid, alendronate gel, and other drugs exhibited anti-inflammatory, antibacterial & osteoblastic differentiation activity. The present systematic review compares the drugs based on their outcomes and pharmacological action. To analzse & compare various forms of local drug delivery systems on a class II furcation. A search was conducted using PubMed, Google scholar, science direct, and Pub Med central using MeSH terms - local drug delivery in periodontics, boric acid in the management of class II mandibular furcation, simvastatin in the treatment of furcation. A total of 560 articles were screened; 58 out of 560 were full-text articles accessed for eligibility, and five articles were included in the systematic review. PRISMA guidelines were used for reporting this review. In addition, five randomized controlled trials were enclosed and used in this systematic review. The various local drugs used in treating class II mandibular furcation defects are effective in the prevention of bleeding on probing, bone resorption, gingival bleeding index and increase in the bone fill, and microbial deposit removal. The managing of class II mandibular furcation defect with the drugs mentioned in this review can be effective by reducing several clinical parameters such as bleeding on probing, gingival indices, osteoblastic differentiation, bone fill, etc., Considering the results of the studies, it can be concluded that it can be used as a therapeutic therapy against class II furcation defects with positive outcomes.
PubMed: 37654351
DOI: 10.4103/jpbs.jpbs_572_22 -
The Cochrane Database of Systematic... Mar 2015Acute kidney injury (AKI) is common in patients undergoing cardiac surgery among whom it is associated with poor outcomes, prolonged hospital stays and increased... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute kidney injury (AKI) is common in patients undergoing cardiac surgery among whom it is associated with poor outcomes, prolonged hospital stays and increased mortality. Statin drugs can produce more than one effect independent of their lipid lowering effect, and may improve kidney injury through inhibition of postoperative inflammatory responses.
OBJECTIVES
This review aimed to look at the evidence supporting the benefits of perioperative statins for AKI prevention in hospitalised adults after surgery who require cardiac bypass. The main objectives were to 1) determine whether use of statins was associated with preventing AKI development; 2) determine whether use of statins was associated with reductions in in-hospital mortality; 3) determine whether use of statins was associated with reduced need for RRT; and 4) determine any adverse effects associated with the use of statins.
SEARCH METHODS
We searched the Cochrane Renal Group's Specialised Register to 13 January 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that compared administration of statin therapy with placebo or standard clinical care in adult patients undergoing surgery requiring cardiopulmonary bypass and reporting AKI, serum creatinine (SCr) or need for renal replacement therapy (RRT) as an outcome were eligible for inclusion. All forms and dosages of statins in conjunction with any duration of pre-operative therapy were considered for inclusion in this review.
DATA COLLECTION AND ANALYSIS
All authors extracted data independently and assessments were cross-checked by a second author. Likewise, assessment of study risk of bias was initially conducted by one author and then by a second author to ensure accuracy. Disagreements were arbitrated among authors until consensus was reached. Authors from two of the included studies provided additional data surrounding post-operative SCr as well as need for RRT. Meta-analyses were used to assess the outcomes of AKI, SCr and mortality rate. Data for the outcomes of RRT and adverse effects were not pooled. Adverse effects taken into account were those reported by the authors of included studies.
MAIN RESULTS
We included seven studies (662 participants) in this review. All except one study was assessed as being at high risk of bias. Three studies assessed atorvastatin, three assessed simvastatin and one investigated rosuvastatin. All studies collected data during the immediate perioperative period only; data collection to hospital discharge and postoperative biochemical data collection ranged from 24 hours to 7 days. Overall, pre-operative statin treatment was not associated with a reduction in postoperative AKI, need for RRT, or mortality. Only two studies (195 participants) reported postoperative SCr level. In those studies, patients allocated to receive statins had lower postoperative SCr concentrations compared with those allocated to no drug treatment/placebo (MD 21.2 µmol/L, 95% CI -31.1 to -11.1). Adverse effects were adequately reported in only one study; no difference was found between the statin group compared to placebo.
AUTHORS' CONCLUSIONS
Analysis of currently available data did not suggest that preoperative statin use is associated with decreased incidence of AKI in adults after surgery who required cardiac bypass. Although a significant reduction in SCr was seen postoperatively in people treated with statins, this result was driven by results from a single study, where SCr was considered as a secondary outcome. The results of the meta-analysis should be interpreted with caution; few studies were included in subgroup analyses, and significant differences in methodology exist among the included studies. Large high quality RCTs are required to establish the safety and efficacy of statins to prevent AKI after cardiac surgery.
Topics: Acute Kidney Injury; Adult; Atorvastatin; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Coronary Artery Bypass; Creatinine; Fluorobenzenes; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Length of Stay; Pyrimidines; Pyrroles; Randomized Controlled Trials as Topic; Renal Replacement Therapy; Rosuvastatin Calcium; Simvastatin; Sulfonamides
PubMed: 25758322
DOI: 10.1002/14651858.CD010480.pub2 -
PloS One 2019Previous research has shown that statin adherence for the primary prevention of CVD is lower compared to secondary prevention populations. Therefore the aim of this...
INTRODUCTION
Previous research has shown that statin adherence for the primary prevention of CVD is lower compared to secondary prevention populations. Therefore the aim of this systematic review was to review predictors of statin adherence for the primary prevention of CVD.
METHODS
A systematic search of papers published between Jan 1984 and May 2017 was conducted in PubMed, PsycINFO, EMbase and CINAHL databases. A study was eligible for inclusion if; 1) it was a study of the general population or of patients with familial hypercholesterolemia, hypertension, diabetes or arthritis; 2) statins were prescribed; 3) adherence was defined and measured as the extent to which patients followed their statin regimen during the period of prescription, and 4) it was an original trial or observational study (excluding case reports). A study was subsequently excluded if 1) results were not presented separately for primary prevention; 2) it was a trial of an intervention (for example patient education). Papers were reviewed by two researchers and consensus agreed with a third. A quality assessment (QA) tool was used to formally assess each included article. To evaluate the effect of predictors, data were quantitatively and qualitatively synthesised.
RESULTS
In total 19 studies met the inclusion criteria and nine were evaluated as high quality using the QA tool. The proportion of patients classed as "adherent" ranged from 17.8% to 79.2%. Potential predictors of statin adherence included traditional risk factors for CVD such as age, being male, diabetes and hypertension. Income associated with adherence more strongly in men than women, and highly educated men were more likely and highly educated women less likely to be adherent. Alcohol misuse and high BMI associated with non-adherence. There was no association between polypharmacy and statin adherence. The evidence base for the effect of other lifestyle factors and health beliefs on statin adherence was limited.
CONCLUSION
Current evidence suggests that patients with more traditional risk factors for CVD are more likely to be adherent to statins. The implications for future research are discussed.
Topics: Aged; Cardiovascular Diseases; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Medication Adherence; Middle Aged; Primary Prevention; Risk Factors
PubMed: 30653535
DOI: 10.1371/journal.pone.0201196