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Cardiovascular Drugs and Therapy Dec 2016
Meta-Analysis Review
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Cholesterol, LDL; Humans; Hypercholesterolemia; PCSK9 Inhibitors
PubMed: 27830381
DOI: 10.1007/s10557-016-6703-0 -
Hemodialysis International.... Jan 2017Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD) and the optimal glycemic control is key to delay the progression of the disease and prevent... (Review)
Review
INTRODUCTION
Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD) and the optimal glycemic control is key to delay the progression of the disease and prevent major complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a promising therapeutic option. However, the benefits and harms of the treatment have yet to be clarified for diabetic patients with CKD.
METHODS
Type 2 diabetic patients with moderate to severe CKD including end-stage renal disease were eligible and randomized controlled trials comparing DPP-4 inhibitors with no treatment or placebo or other antihyperglycemic agents were included. A systematic electronic search was conducted through the Medline Ovid, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov.
FINDINGS
Six placebo/open and 2 active controlled trials (1747 participants) were included. The adjusted mean difference of hemoglobin A between DPP-4 inhibitors and placebo ranged from -0.60% to -0.42%. The odds ratio of hypoglycemia, mortality and severe adverse effects due to all types of DPP-4 inhibitors were 1.35 (95% CI: 0.98-1.84), 0.88 (95% CI: 0.42-1.86) and 0.86 (95% CI: 0.65-1.15), respectively while that due to DPP-4 inhibitors with renal clearance were 1.40 (95% CI: 0.87 to 2.24), 0.85 (95% CI: 0.35 to 2.04) and 0.91 (95% CI: 0.63 to 1.32), respectively.
DISCUSSION
DPP-4 inhibitors demonstrated beneficial effects on the glycemic control for diabetic patients with CKD without causing any additional adverse effects. However, a definitive conclusion has yet to be drawn due to serious methodological problems and a small number of studies.
Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Humans; Hypoglycemic Agents; Middle Aged; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 27436163
DOI: 10.1111/hdi.12438 -
Phytotherapy Research : PTR Aug 2018The objective of this study is to evaluate the efficacy and safety of rhubarb combined with trypsin inhibitor for severe acute pancreatitis (SAP). This meta-analysis was... (Meta-Analysis)
Meta-Analysis Review
The objective of this study is to evaluate the efficacy and safety of rhubarb combined with trypsin inhibitor for severe acute pancreatitis (SAP). This meta-analysis was performed in accordance with the Transparent Reporting of Systematic Reviews and Meta-analysis protocol (PRISMA-P) and Cochrane Handbook. Relevant studies from inception to 2016 were searched through 7 related databases. The Cochrane Library was searched to assess the bias of the included trials. Data were analysed with Review Manager 5.3 software. A total of 16 randomized controlled trials (RCTs) involving 912 participants with SAP were included in this meta-analysis. The result showed that when compared with trypsin inhibitor used alone, rhubarb combined with trypsin inhibitor showed intensive effects on decreasing mortality, increasing overall efficacy, shorting length of hospitalization, reducing abdominal pain relief time, and decreasing the level of serum amylase. There was no serious adverse event reported in these RCTs. It should be noted that potential publication bias was observed. This meta-analysis demonstrated that rhubarb combined with trypsin inhibitor could be an effective and safe treatment for patients with SAP. However, the small sample size and poor quality of these RCTs should be noted. And more rigorously designed, multicentre, large-scale worldwide trials with more practitioners and higher quality are required.
Topics: Acute Disease; Humans; Pancreatitis; Plant Preparations; Randomized Controlled Trials as Topic; Rheum; Trypsin Inhibitors
PubMed: 29672966
DOI: 10.1002/ptr.6096 -
Journal of the American Heart... Oct 2017The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab substantially reduce low-density lipoprotein cholesterol (LDL-C) when... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab substantially reduce low-density lipoprotein cholesterol (LDL-C) when added to statin therapy in patients who need additional LDL-C reduction.
METHODS AND RESULTS
We conducted a systematic review and network meta-analysis of randomized trials of lipid-lowering therapies from database inception through August 2016 (45 058 records retrieved). We found 69 trials of lipid-lowering therapies that enrolled patients requiring further LDL-C reduction while on maximally tolerated medium- or high-intensity statin, of which 15 could be relevant for inclusion in LDL-C reduction networks with evolocumab, alirocumab, ezetimibe, and placebo as treatment arms. PCSK9 inhibitors significantly reduced LDL-C by 54% to 74% versus placebo and 26% to 46% versus ezetimibe. There were significant treatment differences for evolocumab 140 mg every 2 weeks at the mean of weeks 10 and 12 versus placebo (-74.1%; 95% credible interval -79.81% to -68.58%), alirocumab 75 mg (-20.03%; 95% credible interval -27.32% to -12.96%), and alirocumab 150 mg (-13.63%; 95% credible interval -22.43% to -5.33%) at ≥12 weeks. Treatment differences were similar in direction and magnitude for PCSK9 inhibitor monthly dosing. Adverse events were similar between PCSK9 inhibitors and control. Rates of adverse events were similar between PCSK9 inhibitors versus placebo or ezetimibe.
CONCLUSIONS
PCSK9 inhibitors added to medium- to high-intensity statin therapy significantly reduce LDL-C in patients requiring further LDL-C reduction. The network meta-analysis showed a significant treatment difference in LDL-C reduction for evolocumab versus alirocumab.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Biomarkers; Cardiovascular Diseases; Down-Regulation; Drug Therapy, Combination; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Lipids; Male; Middle Aged; PCSK9 Inhibitors; Proprotein Convertase 9; Randomized Controlled Trials as Topic; Risk Factors; Serine Proteinase Inhibitors; Treatment Outcome
PubMed: 28971955
DOI: 10.1161/JAHA.116.005367 -
BMJ Open Respiratory Research Aug 2023Current evidence on the effectiveness of SARS-CoV-2 prophylaxis is inconclusive. We aimed to systematically evaluate published studies on repurposed drugs for the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Current evidence on the effectiveness of SARS-CoV-2 prophylaxis is inconclusive. We aimed to systematically evaluate published studies on repurposed drugs for the prevention of laboratory-confirmed SARS-CoV-2 infection and/or COVID-19 among healthy adults.
DESIGN
Systematic review.
ELIGIBILITY
Quantitative experimental and observational intervention studies that evaluated the effectiveness of repurposed drugs for the primary prevention of SARS-CoV-2 infection and/or COVID-19 disease.
DATA SOURCE
PubMed and Embase (1 January 2020-28 September 2022).
RISK OF BIAS
Cochrane Risk of Bias 2.0 and Risk of Bias in Non-Randomised Studies of Interventions tools were applied to assess the quality of studies.
DATA ANALYSIS
Meta-analyses for each eligible drug were performed if ≥2 similar study designs were available.
RESULTS
In all, 65 (25 trials, 40 observational) and 29 publications were eligible for review and meta-analyses, respectively. Most studies pertained to hydroxychloroquine (32), ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) (11), statin (8), and ivermectin (8). In trials, hydroxychloroquine prophylaxis reduced laboratory-confirmed SARS-CoV-2 infection (risk ratio: 0.82 (95% CI 0.74 to 0.90), I=48%), a result largely driven by one clinical trial (weight: 60.5%). Such beneficial effects were not observed in observational studies, nor for prognostic clinical outcomes. Ivermectin did not significantly reduce the risk of SARS-CoV-2 infection (RR: 0.35 (95% CI 0.10 to 1.26), I=96%) and findings for clinical outcomes were inconsistent. Neither ACEi or ARB were beneficial in reducing SARS-CoV-2 infection. Most of the evidence from clinical trials was of moderate quality and of lower quality in observational studies.
CONCLUSIONS
Results from our analysis are insufficient to support an evidence-based repurposed drug policy for SARS-CoV-2 prophylaxis because of inconsistency. In the view of scarce supportive evidence on repurposing drugs for COVID-19, alternative strategies such as immunisation of vulnerable people are warranted to prevent the future waves of infection.
PROSPERO REGISTRATION NUMBER
CRD42021292797.
Topics: Adult; Humans; COVID-19; Pandemics; SARS-CoV-2; Angiotensin Receptor Antagonists; Hydroxychloroquine; Ivermectin; Angiotensin-Converting Enzyme Inhibitors; Primary Prevention
PubMed: 37640510
DOI: 10.1136/bmjresp-2023-001674 -
International Journal of STD & AIDS Dec 2023Protease inhibitors (PIs) have contributed to the long-term survival of persons with human immunodeficiency virus (PHIV). While there is a concern linking protease...
BACKGROUND
Protease inhibitors (PIs) have contributed to the long-term survival of persons with human immunodeficiency virus (PHIV). While there is a concern linking protease inhibitors to an increased risk of heart failure (HF), the evidence linking protease inhibitors and heart failure has been uncertain.
METHODS
Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for peer-reviewed articles using keywords including "protease inhibitor," "heart failure," and "human immunodeficiency virus" from their inception to December 21, 2022.
RESULTS
Five articles, including three observational studies and two randomized controlled trials, were included in the review. While protease inhibitors seem to be associated with atherosclerotic cardiovascular disease through their effects on metabolic markers, there is scarce evidence suggesting a direct association between protease inhibitors and heart failure. Although one study showed a possible correlation between protease inhibitor use and lower left ventricular ejection fraction and increased heart failure admission, the results were subject to confounders, and participants had poor medication adherence.
CONCLUSION
Although current data are conflicting, there could be an association between PIs and HF in PHIV. Future prospective studies are warranted to evaluate the incidence of heart failure stratified on the generation of PIs and with adjustment for other metabolic risk factors.
Topics: Humans; Protease Inhibitors; Stroke Volume; Ventricular Function, Left; Heart Failure; Risk Factors; Antiviral Agents; HIV; Anti-Infective Agents
PubMed: 37608625
DOI: 10.1177/09564624231196599 -
World Journal of Gastroenterology Mar 2015To evaluate the benefit and safety of sivelestat (a neutrophil elastase inhibitor) administration in patients undergoing esophagectomy. (Meta-Analysis)
Meta-Analysis Review
AIM
To evaluate the benefit and safety of sivelestat (a neutrophil elastase inhibitor) administration in patients undergoing esophagectomy.
METHODS
Online databases including PubMed, EMBASE, the Cochrane Library, Web of Knowledge, and Chinese databases (Wanfang database, VIP and CNKI) were searched systematically up to November 2013. Randomized controlled trials and high-quality comparative studies were considered eligible for inclusion. Three reviewers evaluated the methodological quality of the included studies, and Stata 12.0 software was used to analyze the extracted data. The risk ratio (RR) was used to express the effect size of dichotomous outcomes, and mean difference (MD) or standardized mean difference was used to express the effect size of continuous outcomes.
RESULTS
Thirteen studies were included in this systematic review and nine studies were included in the meta-analysis. The duration of mechanical ventilation was significantly decreased in the sivelestat group on postoperative day 5 [I (2) = 76.3%, SMD = -1.41, 95%CI: -2.63-(-0.19)]. Sivelestat greatly lowered the incidence of acute lung injury in patients after surgery (I (2) = 0%, RR = 0.27, 95%CI: 0.08-0.93). However, it did not decrease the incidence of pneumonia, intensive care unit stay or postoperative hospital stay, and did not increase the incidence of complications such as anastomotic leakage, recurrent nerve palsy, wound infection, sepsis and catheter-related fever.
CONCLUSION
A neutrophil elastase inhibitor is beneficial in patients undergoing esophagectomy. More high quality, large sample, multi-center and randomized controlled trials are needed to validate this effect.
Topics: Acute Lung Injury; Aged; Esophagectomy; Female; Glycine; Humans; Leukocyte Elastase; Male; Middle Aged; Odds Ratio; Respiration, Artificial; Risk Factors; Serine Proteinase Inhibitors; Sulfonamides; Time Factors; Treatment Outcome
PubMed: 25834341
DOI: 10.3748/wjg.v21.i12.3720 -
Diabetes Research and Clinical Practice Jun 2016Fracture risk is higher in older adults with Type 2 diabetes mellitus (T2DM). Oral glucose-lowering medications have different effects on bone metabolism. The purpose of... (Meta-Analysis)
Meta-Analysis Review
AIM
Fracture risk is higher in older adults with Type 2 diabetes mellitus (T2DM). Oral glucose-lowering medications have different effects on bone metabolism. The purpose of this study is to appraise the evidence from literature and determine the effect of dipeptidyl peptidase-4 (DPP-4) inhibitor on the risk of developing bone fractures.
METHODS
Using Boolean search terms, the search strategy combined synonyms of 'fracture' and 'DPP-4 inhibitor'. Comprehensive electronic databases which include EMBASE, MEDLINE, the EMA and the WHO ICTRP databases were searched for randomised controlled trial (RCT) studies which compared a DPP-4 inhibitor with an active comparator or placebo amongst patients with T2DM. Meta-analysis was performed to compare DPP-4 inhibitor with either an active comparator or a placebo. The outcome measure was the presence or absence of fracture.
RESULTS
The search yielded 5061 records relating to fractures and DPP-4 inhibitor, from which 51 eligible RCTs were selected for meta-analysis (N=36,402). Thirty-seven (37) studies compared DPP-4 inhibitor with placebo (n=23,974), while fourteen (14) studies (n=12,428) compared DPP-4 inhibitor with an active comparator. The mean age of patients was 57.5±5.4years, the average glycated haemoglobin (HbA1c) was 8.2%, while the average BMI was 30±2kg/m(2). Overall, there was no significant association of fracture events with the use of DPP-4 inhibitor when compared with placebo (OR; 0.82, 95% CI 0.57-1.16, P=0.9) or when DPP-4 inhibitor was compared against an active comparator (OR; 1.59, 95% CI 0.91-2.80, P=0.9).
CONCLUSION
This study offers a larger, up-to-date review of the subject. The meta-analysis showed that there was no significant association between DPP-4 inhibitor use and the incidence of fractures.
Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Fractures, Bone; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Randomized Controlled Trials as Topic
PubMed: 27321347
DOI: 10.1016/j.diabres.2016.04.029 -
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 -
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