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CNS Neuroscience & Therapeutics Jul 2023Serpin is a superfamily of serine proteinase inhibitors. They have anticoagulative activities and immunoregulatory effects. The family has been widely studied in stroke... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Serpin is a superfamily of serine proteinase inhibitors. They have anticoagulative activities and immunoregulatory effects. The family has been widely studied in stroke patients and animal stroke models. However, results from clinical and preclinical studies are controversial. The systematic review and meta-analysis aimed to determine whether serpin activities are affected by stroke and whether members of the serpin family could be used in stroke treatment.
METHODS
Literature was systematically searched in six databases until September 5, 2022. In the included studies, 47 clinical studies (8276 subjects) reported concentrations of serpin proteins in stroke patients and healthy controls. In total, 41 preclinical studies (742 animals) reported neurological outcomes in animal models with serpin treatment and vehicle.
RESULTS
Meta-analysis of clinical studies showed that both ischemic (IS) and hemorrhagic stroke patients had higher thrombin-antithrombin complex (TAT) levels and lower antithrombin (AT) levels which were persistent in the acute and subacute phase of IS. Meta-analysis of preclinical studies reported the efficacy of serpins in treating stroke. C1-INH and FUT175 reduced brain infarct size and improved sensorimotor and motor behavior in a dose- and time-dependent manner in the MCAO models.
CONCLUSIONS
Our study confirmed the important roles serpin family proteins played in the onset, progression, and treatment of stroke. Among serpins, AT and TAT may be used as blood biomarkers in the early diagnosis of stroke. C1-INH and FUT175 could be potential medications for IS.
Topics: Animals; Serpins; Biomarkers; Models, Animal; Stroke
PubMed: 37017398
DOI: 10.1111/cns.14205 -
Current Problems in Cardiology May 2023Heart failure is a growing global health concern with high mortality and morbidity. Beta-blockers, mineralocorticoid receptor antagonists, and... (Review)
Review
Heart failure is a growing global health concern with high mortality and morbidity. Beta-blockers, mineralocorticoid receptor antagonists, and angiotensin-converting-enzyme inhibitors are the treatments of choice for worsening clinical symptoms. In early 2021, the FDA approved a new oral soluble guanylate cyclase stimulator, Vericiguat, for the treatment of chronic heart failure. To evaluate the efficacy and safety of this approved drug, we conducted a systematic review of the available randomized controlled trials (RCTs). A literature search was conducted using PubMed, The Cochrane Library, and Clinicaltrials.gov from inception to June 6, 2022, without any language restriction. The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The quality of the included studies was checked using the Cochrane Risk-of-Bias tool. After a thorough literature search, 7 studies met our pre-defined criteria and were therefore included in this review. Our review suggests that vericiguat was better in preventing all causes of death, cardiovascular death, and hospitalizations due to heart failure irrespective of the atrial fibrillation status of the patients and was even beneficial for patients with NT-proBNP levels up to 8000 pg/ml. The safety of the vericiguat, according to our review, is not up to the standards, especially with a higher dosage of vericiguat. Despite all of this, vericiguat can be a breakthrough in the treatment of heart failure as it has great potential to improve the disease severity.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Adrenergic beta-Antagonists; Heterocyclic Compounds, 2-Ring; Heart Failure; Stroke Volume
PubMed: 36623755
DOI: 10.1016/j.cpcardiol.2023.101586 -
Advances in Therapy Jan 2012Lipid profile is an important determinant of cardiovascular risk in type 2 diabetic patients. Available glucose-lowering agents can affect lipid levels. Dipeptidyl... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Lipid profile is an important determinant of cardiovascular risk in type 2 diabetic patients. Available glucose-lowering agents can affect lipid levels. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to reduce total cholesterol, but results are inconsistent across trials. The present metaanalysis was designed to assess the effect of DPP-4 inhibitors on blood lipids, verifying possible differences across compounds of this class.
METHODS
An extensive search of Medline and the Cochrane Library (any date up to December 31, 2010, restricted to randomized clinical trials, published in English) was performed for all trials containing, in any field, the words "sitagliptin," "vildagliptin," "saxagliptin," "alogliptin," "linagliptin," and/or "dutogliptin." Completed but unpublished trials were identified through a search of the ClinicalTrials.gov website, using the same keywords as above. Differences in the endpoint levels and absolute or percent variations of lipids were assessed. A metaregression was performed on the trials specified above to assess the effect of putative moderators on the effect of DPP-4 inhibitors on plasma lipids, considering all drugs together and each one separately.
RESULTS
Although the number of trials of appropriate size and duration was high (n=53), only a small fraction of those (n=17) reported data on endpoint total, high-density lipoprotein, and low-density lipoprotein cholesterol, and triglyceride. The difference-in-means for endpoint versus baseline total cholesterol in patients on DPP-4 inhibitors treatment was significantly higher in comparison with controls, meaning that treatment with DPP-4 inhibitors is associated with a significant reduction in total cholesterol (-0.18 [-0.29; -0.06] mmol/L (-7.0 [-11.2; -2.50] mg/dL); P=0.002).
CONCLUSIONS
This meta-analysis suggests a possible beneficial effect of DPP-4 inhibitors on cholesterol, which, although small, could contribute to the reduction of cardiovascular risk.
Topics: Cardiovascular Diseases; Diabetes Mellitus; Dipeptidyl-Peptidase IV Inhibitors; Humans; Lipid Metabolism; Lipoproteins, HDL; Lipoproteins, LDL; Triglycerides
PubMed: 22215383
DOI: 10.1007/s12325-011-0088-z -
Infectious Diseases and Therapy Jan 2015Despite antiretroviral (ARV) therapy reducing renal disease in human immunodeficiency virus overall, there is concern that certain ARVs, particularly tenofovir...
INTRODUCTION
Despite antiretroviral (ARV) therapy reducing renal disease in human immunodeficiency virus overall, there is concern that certain ARVs, particularly tenofovir disoproxil fumarate (TDF) with or without a boosted protease inhibitor (PI), may reduce renal function over time. It is not known whether effects seen with PI-based regimens are independent, result from interactions with TDF coadministration, or are artefactual owing to inhibition of renal tubular creatinine transport by ritonavir or cobicistat pharmacoenhancement. The aim of this review was to conduct a systematic review of studies, weighted toward high-quality evidence, examining changes in renal function over time with PI-based regimens.
METHODS
PubMed, Embase, and Medline databases and conference abstracts were searched using pre-defined terms for English language articles, published up to and including August 12, 2013, describing changes in renal function over time with PI-based regimens. All available randomized controlled trials (RCTs) were selected; however, to reduce bias, only observational studies recruiting from more than one center and analyzing data from more than 1,000 patients were included. Evidence was qualitatively evaluated according to levels established by the Oxford Centre for Evidence-Based Medicine (OCEBM).
RESULTS
A total of 2,322 articles were retrieved by the initial search. Of these, 37 were selected for full review, comprising 24 RCTs (OCEBM Level 1 evidence: 4 reports of fully double-blinded or blinded with respect to the PI component). The remaining 20 RCTs and 13 observational studies qualified as OCEBM Level 2 evidence. Level 1 evidence showed initial but non-progressive increases in serum creatinine and corresponding decreases in estimated glomerular filtration rate (eGFR), suggesting an effect on renal tubular transport of creatinine. Level 2 evidence suggested that atazanavir and lopinavir especially in combination with TDF were associated with non-progressive reductions in eGFR over time, with a decreased risk for the development of chronic kidney disease (CKD) on cessation and without the development of advanced CKD or end-stage renal disease (ESRD); whether these reductions were independent or associated with interactions with coadministered TDF could not be established with certainty. Data on darunavir were insufficient to draw any conclusions. The principal limitation of the reviewed studies was the lack of standardization of creatinine measurements in virtually all studies and the lack of corroborative data on changes in proteinuria or other indices of renal function.
DISCUSSION
In this review, there was little evidence for progressive changes in eGFR, or the development of advanced CKD, or ESRD with lopinavir or atazanavir. Further long-term studies, employing a wide range of validated renal function assessments, are required to fully evaluate potential association of PIs with CKD.
PubMed: 25567681
DOI: 10.1007/s40121-014-0056-4 -
Journal of Dental Research Aug 2014The aim of this study was to systematically review the literature for in vitro and ex vivo studies that evaluated the effect of matrix metalloproteinase (MMP) inhibitors... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to systematically review the literature for in vitro and ex vivo studies that evaluated the effect of matrix metalloproteinase (MMP) inhibitors during the adhesive procedure on the immediate and long-term resin-dentin bond strength. The search was conducted in 6 databases with no publication year or language limits, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. From 1,336 potentially eligible studies, 48 were selected for full-text analysis, and 30 were included for review, with 17 considered in the meta-analysis. Two reviewers independently selected the studies, extracted the data, and assessed the risk of bias. Pooled effect estimates were expressed as the weighted mean difference between groups. The most used MMP inhibitor was chlorhexidine (CHX). Immediate bond strength results showed no difference between 2% CHX and control; however, a difference was found between 0.2% CHX and control at baseline. After aging, CHX presented higher bond strength values compared to control groups (p < .05). However, this was not observed for longer periods of aging. High heterogeneity was found in some comparisons, especially for the water storage aging subgroup. Subgroup analyses showed that self-etching and etch-and-rinse adhesives are benefited by the CHX use. From the studies included, only 1 presented low risk of bias, while the others showed medium or high risk of bias. The use of MMP inhibitors did not affect the immediate bond strength overall, while it influenced the aged bond strength. Aging procedures influenced bond strength values of the dentin adhesion stability.
Topics: Acid Etching, Dental; Chlorhexidine; Dental Bonding; Dentin; Humans; Matrix Metalloproteinase Inhibitors; Stress, Mechanical; Time Factors
PubMed: 24935066
DOI: 10.1177/0022034514538046 -
Scientific Reports Oct 2022Currently, there is no specific pharmaceutical agent for treating acute pancreatitis (AP). Somatostatin and its analogues have been used to prevent the autolysis of the... (Meta-Analysis)
Meta-Analysis
Currently, there is no specific pharmaceutical agent for treating acute pancreatitis (AP). Somatostatin and its analogues have been used to prevent the autolysis of the pancreas in AP, however, their effectiveness has not been confirmed. This investigation aimed to examine the efficacy of ulinastatin, a protease inhibitor, combined with somatostatin analogues in the treatment of AP. We conducted a systematic database search in 4 databases to identify randomized controlled trials in which the efficacy of ulinastatin in combination with somatostatin analogue was compared to somatostatin analogue alone in patients with AP. Since the patient populations of analysed papers were slightly different, we used random effect models to pool odds ratios (OR) and mean differences (MD) and the corresponding 95% confidence intervals (CI). A total of 9 articles comprising 1037 patients were included in the meta-analysis. The combination therapy significantly reduced the complication rates for acute respiratory distress syndrome, acute kidney injury, and multiple organ dysfunction. Symptoms were relieved threefold with the combination therapy compared to somatostatin alone, and combination therapy significantly shortened the length of hospital stay. The decrease in mortality was not statistically significant..
Topics: Humans; Acute Disease; Pancreatitis; Protease Inhibitors; Randomized Controlled Trials as Topic; Somatostatin
PubMed: 36289288
DOI: 10.1038/s41598-022-22341-7 -
Frontiers in Bioscience (Landmark... Dec 2023Plasma renin activity (PRA) has gained relevance as prognostic marker in adults with heart failure. The use of PRA as a clinically meaningful parameter in children and...
BACKGROUND
Plasma renin activity (PRA) has gained relevance as prognostic marker in adults with heart failure. The use of PRA as a clinically meaningful parameter in children and children with heart failure requires a thorough knowledge of the factors that influence PRA to correctly assess PRA levels. We aim to evaluate the influence of age, heart failure and angiotensin-converting enzyme inhibitor (ACEi) on PRA levels in children.
METHODS
We conducted a systematic literature search to identify studies on PRA levels in healthy children and in children with heart failure. In addition, we analysed PRA data measured before (n = 35, aged 25 days-2.1 years), 4 hours after (n = 34) and within the first 8 days of enalapril treatment (n = 29) in children with heart failure from the European project Labeling of Enalapril from Neonates up to Adolescents (LENA).
RESULTS
Age has a profound effect on PRA levels in healthy children, as PRA levels in the literature are up to about 7 times higher in neonates than in older children. Children with heart failure younger than 6 months showed 3-4 times higher PRA levels than healthy peers in both the literature and the LENA studies. In the LENA studies, the ACEi enalapril significantly increased median predose PRA by a factor of 4.5 in children with heart failure after 4.7 ± 1.6 days of treatment (n = 29, < 0.01). Prior to treatment with enalapril, LENA subjects with symptomatic heart failure (Ross score ≥3) had a significantly higher PRA than LENA subjects with asymptomatic heart failure of comparable age (Ross score ≤2, < 0.05).
CONCLUSIONS
Age, heart failure and ACEi treatment have a notable influence on PRA and must be considered when assessing PRA as a clinically meaningful parameter.
CLINICAL TRIAL REGISTRATION
The trials are registered on the EU Clinical Trials Register (https://www.clinicaltrialsregister.eu).
TRIAL REGISTRATION NUMBERS
EudraCT 2015-002335-17, EudraCT 2015-002396-18.
Topics: Humans; Infant, Newborn; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Heart Failure; Renin; Renin-Angiotensin System; Infant; Child, Preschool
PubMed: 38179766
DOI: 10.31083/j.fbl2812335 -
Postgraduate Medicine Mar 2017We aim to conduct a meta-analysis, by stratifying diabetic patients with or without clinical cardiovascular diseases (CVD), to explore whether there are different... (Meta-Analysis)
Meta-Analysis Review
Cardiovascular effects of dipeptidyl peptidase-4 inhibitor in diabetic patients with and without established cardiovascular disease: a meta-analysis and systematic review.
OBJECTIVES
We aim to conduct a meta-analysis, by stratifying diabetic patients with or without clinical cardiovascular diseases (CVD), to explore whether there are different cardiovascular effects of dipeptidyl peptidase-4 inhibitors (DPP-4is) on these two different classes of diabetic patients.
METHODS
We searchedMedline,Embase, theCochrane Libraryand ClinicalTrials.gov for relevant randomized controlled trials (RCTs). The included trials are divided into CVD (+) trials (subjects with established CVD), and CVD (-) trials (subjects with no CVD). We use all-cause mortality and cardiovascular outcomes as primary endpoints.
RESULTS
(1) Three CVD (+) trials were included and 36,895 subjects were enrolled with a mean follow-up duration of 127.1 weeks. The pooled results showed that DPP-4is treatment, compared with the placebo, did not significantly affect all-cause mortality (RR, 1.03; 95% CI, 0.95 to 1.11), cardiovascular death (1.01, 0.91 to 1.12), myocardial infarction (0.98, 0.88 to 1.08) or stroke (1.02, 0.88 to 1.18) in diabetic patients with coexisting CVD history; however, it significantly increased the risk of heart failure (1.14, 1.01 to 1.27) in this population. 2) Thirty-five CVD (-) trials were included, and 29,600 patients were enrolled with a mean follow-up duration of 77.8 weeks. The analysis comparing DPP-4is with the placebo control showed that DPP-4is treatment did not significantly affect the risk of all-cause mortality or cardiovascular outcomes in diabetic patients free of CVD history. However, when compared with the active control, the pooling data showed that DPP-4is had a significant reduction on the risk of stroke (0.58, 0.34 to 0.99) but did not significantly affect the risk of all-cause mortality and other cardiovascular outcomes.
CONCLUSION
DPP-4is may have no cardiovascular protective effects in diabetic patients with coexisting CVD, while there is a lack of definitive evidence supporting the cardiovascular benefits of DPP-4is treatment among diabetic patients free of CVD history.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Randomized Controlled Trials as Topic
PubMed: 27813442
DOI: 10.1080/00325481.2017.1255537 -
BMC Gastroenterology May 2014The intravenous use of protease inhibitors in patients with acute pancreatitis is still controversial. The purpose of this study was to evaluate the effectiveness of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The intravenous use of protease inhibitors in patients with acute pancreatitis is still controversial. The purpose of this study was to evaluate the effectiveness of protease inhibitors intravenously administered to prevent pancreatitis-associated complications.
METHODS
We updated our previous meta-analysis with articles of randomized controlled trials published from January 1965 to March 2013 on the effectiveness of protease inhibitors for acute pancreatitis. A systematic search of PubMed, EMBASE, the Cochrane Library, and Japana Centra Revuo Medicina was conducted. In addition, Internet-based registries (ClinicalTrials.gov, controlled-trials.com, UMIN, JMACCT, and JAPIC) were used to search for on-going clinical trials. Furthermore, references of review articles and previously published meta-analyses were handsearched. The main outcome of interest was the overall mortality rate from acute pancreatitis.
RESULTS
Seventeen trials were selected for analysis. Overall, protease inhibitors did not achieve a significant risk reduction in mortality (pooled risk difference [RD], -0.02; 95% Confidence Interval [CI], -0.05 to 0.01; number needed to treat [NNT], 74.8) with low heterogeneity. A subgroup analysis in moderate to severe pancreatitis (defined by control mortality rate [CMR] >0.10) did not show a significant effect of protease inhibitors to prevent death (pooled RD, -0.03; 95% CI, -0.07 to 0.01; NNT, 1603.9) with low heterogeneity. An additional subgroup analysis of two trials with CMR >0.20 (i.e., low quality) revealed a significant risk reduction.
CONCLUSION
The present meta-analysis re-confirmed that there is no solid evidence that supports the intravenous use of protease inhibitors to prevent death due to acute pancreatitis.
Topics: Acute Disease; Aprotinin; Gabexate; Humans; Infusions, Intravenous; Pancreatitis; Protease Inhibitors; Serine Proteinase Inhibitors; Severity of Illness Index; Treatment Outcome
PubMed: 24886242
DOI: 10.1186/1471-230X-14-102 -
Medicina (Kaunas, Lithuania) Jun 2023Angiotensin II-converting enzyme inhibitors (ACEIs) and selective angiotensin II receptor antagonists (ARAIIs) are widely used antihypertensive agents. Their use has... (Meta-Analysis)
Meta-Analysis Review
Angiotensin II-converting enzyme inhibitors (ACEIs) and selective angiotensin II receptor antagonists (ARAIIs) are widely used antihypertensive agents. Their use has generated controversy due to their possible influence on the health status of chronic patients infected with COVID-19. The objective of this work is to analyze the influence of COVID-19 on chronic hypertensive patients treated with ACEI and ARAII inhibitors. A systematic review and meta-analysis in the databases Pubmed, Pro-Quest and Scopus were carried out. The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search equation descriptors were obtained from the Medical Subject Headings (MeSH) thesaurus. The search equation was: "Older AND hypertension AND (COVID-19 OR coronavirus) AND primary care" and its equivalent in Spanish. Nineteen articles were obtained, with n = 10,806,159 subjects. Several studies describe the COVID-19 association with ACEI or ARAII treatment in hypertension patients as a protective factor, some as a risk factor, and others without a risk association. In the case of ACEI vs. ARAII, the risk described for the former has an odds ratio (OR) of 0.55, and for ARAII, an OR of 0.59. Some authors talk about mortality associated with COVID-19 and ACEI with a half ratio (HR) of 0.97, and also associated ARAIIs with an HR of 0.98. It is recommended to maintain the use of the renin-angiotensin-aldosterone axis in the context of the COVID-19 disease.
Topics: Humans; Aged; COVID-19; Angiotensin Receptor Antagonists; SARS-CoV-2; Angiotensin-Converting Enzyme Inhibitors; Hypertension
PubMed: 37512012
DOI: 10.3390/medicina59071200