-
European Journal of Pharmacology Oct 2020Sacubitril/valsartan (LCZ696) is recommended for ejection fraction reduction in heart failure. However, studies comparing the effects of sacubitril/valsartan in patients... (Meta-Analysis)
Meta-Analysis
Sacubitril/valsartan (LCZ696) is recommended for ejection fraction reduction in heart failure. However, studies comparing the effects of sacubitril/valsartan in patients with heart failure and chronic kidney disease (CKD) with the inhibitor of renal angiotensin system (RAS) are limited. To further demonstrate the benefits of sacubitril/valsartan in patients with both heart failure and CKD, a meta-analysis of randomized controlled trials (RCTs) was conducted. The Cochrane Library, PubMed, Web of Science and ClinicalTrials.gov were searched for RCTs. A total of 3460 individuals with heart failure and CKD were included in this meta-analysis. Sacubitril/valsartan was compared with irbesartan, valsartan and enalapril. It was found that sacubitril/valsartan significantly increased estimated glomerular filtration rate [eGFR, MD = 1.90, 95% CI (0.30, 3.50), P = 0.02]. However, sacubitril/valsartan had no difference in urinary albumin/creatinine ratio [UACR, MD = -0.30, 95% CI (-1.38, 0.78), P = 0.59] compared to the control group. Sacubitril/valsartan showed dramatically decrease in systolic blood pressure [SBP, MD = -4.39, 95% CI (-6.11, -2.68), P < 0.001], diastolic blood pressure [DBP, MD = -2.69, 95% CI (-4.04, -1.35), P < 0.001], and N-terminal prohormone brain natriuretic peptide [NT-proBNP, MD = -45.34, 95% CI (-46.63, -44.06), P < 0.001]. There was no significant difference in the incidence of adverse reactions between sacubitril/valsartan and the control group. Compared with the RAS inhibitor, sacubitril/valsartan significantly increased eGFR and decreased BP and NT-proBNP, which indicates that it might have cardiovascular and renal benefits in patients with heart failure and CKD.
Topics: Aged; Aged, 80 and over; Aminobutyrates; Angiotensin II Type 1 Receptor Blockers; Biphenyl Compounds; Drug Combinations; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Male; Middle Aged; Neprilysin; Protease Inhibitors; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Stroke Volume; Treatment Outcome; Valsartan
PubMed: 32739172
DOI: 10.1016/j.ejphar.2020.173444 -
ESC Heart Failure Feb 2024Guideline-directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin-angiotensin-aldosterone system inhibitors,... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of new potassium binders on renin-angiotensin-aldosterone system inhibitor optimization in heart failure patients: a systematic review and meta-analysis.
Guideline-directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin-angiotensin-aldosterone system inhibitors, which can hinder the excretion of potassium, resulting in hyperkalaemia. New potassium binders (NPBs) can prevent this adverse effect; however, the efficacy and safety of NPB for this indication have not been fully established. We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through 26 April 2023. The risk of bias assessment was conducted, following Cochrane's updated Risk of Bias 2 assessment tool. We used the fixed-effects model to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI) (PROSPERO ID: CRD42023426113). We included six RCTs with a total of 1432 patients. NPB was significantly associated with successful mineralocorticoid receptor antagonist (MRA) optimization [RR: 1.13 with 95% CI (1.02-1.25), P = 0.02], decreased patients with MRA at less than the target dose [RR: 0.72 with 95% CI (0.57-0.90), P = 0.004], and decreased hyperkalaemic episodes [RR: 0.42 with 95% CI (0.24-0.72), P = 0.002]. However, there was no difference between NPB and placebo regarding angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/angiotensin receptor/neprilysin inhibitor (ANRi) optimization [RR: 1.02 with 95% CI (0.89-1.17), P = 0.76] and serum potassium change [MD: -0.31 with 95% CI (-0.61 to 0.00), P = 0.05], with an acceptable safety profile except for the increased incidence of hypokalaemia with NPB [RR: 1.57 with 95% CI (1.12-2.21), P = 0.009]. NPB has been shown to improve GDMT outcomes by enhancing MRA optimization and reducing hyperkalaemic episodes. However, there are limited data on the effects of NPB on ACEi/ARB/ANRi optimization. Future RCTs should investigate ACEi/ARB/ANRi optimization and conduct head-to-head comparisons of NPB (patiromer and sodium zirconium cyclosilicate).
Topics: Humans; Aldosterone; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Heart Failure; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Potassium; Renin-Angiotensin System
PubMed: 38012095
DOI: 10.1002/ehf2.14588 -
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 -
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 -
The Cochrane Database of Systematic... Nov 2017Chronic kidney disease (CKD) is an independent risk factor for atrial fibrillation (AF), which is more prevalent among CKD patients than the general population. AF... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic kidney disease (CKD) is an independent risk factor for atrial fibrillation (AF), which is more prevalent among CKD patients than the general population. AF causes stroke or systemic embolism, leading to increased mortality. The conventional antithrombotic prophylaxis agent warfarin is often prescribed for the prevention of stroke, but risk of bleeding necessitates regular therapeutic monitoring. Recently developed direct oral anticoagulants (DOAC) are expected to be useful as alternatives to warfarin.
OBJECTIVES
To assess the efficacy and safety of DOAC including apixaban, dabigatran, edoxaban, and rivaroxaban versus warfarin among AF patients with CKD.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Specialised Register (up to 1 August 2017) through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) which directly compared the efficacy and safety of direct oral anticoagulants (direct thrombin inhibitors or factor Xa inhibitors) with dose-adjusted warfarin for preventing stroke and systemic embolic events in non-valvular AF patients with CKD, defined as creatinine clearance (CrCl) or eGFR between 15 and 60 mL/min (CKD stage G3 and G4).
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, assessed quality, and extracted data. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for the association between anticoagulant therapy and all strokes and systemic embolic events as the primary efficacy outcome and major bleeding events as the primary safety outcome. Confidence in the evidence was assessing using GRADE.
MAIN RESULTS
Our review included 12,545 AF participants with CKD from five studies. All participants were randomised to either DOAC (apixaban, dabigatran, edoxaban, and rivaroxaban) or dose-adjusted warfarin. Four studies used a central, interactive, automated response system for allocation concealment while the other did not specify concealment methods. Four studies were blinded while the other was partially open-label. However, given that all studies involved blinded evaluation of outcome events, we considered the risk of bias to be low. We were unable to create funnel plots due to the small number of studies, thwarting assessment of publication bias. Study duration ranged from 1.8 to 2.8 years. The large majority of participants included in this study were CKD stage G3 (12,155), and a small number were stage G4 (390). Of 12,545 participants from five studies, a total of 321 cases (2.56%) of the primary efficacy outcome occurred per year. Further, of 12,521 participants from five studies, a total of 617 cases (4.93%) of the primary safety outcome occurred per year. DOAC appeared to probably reduce the incidence of stroke and systemic embolism events (5 studies, 12,545 participants: RR 0.81, 95% CI 0.65 to 1.00; moderate certainty evidence) and to slightly reduce the incidence of major bleeding events (5 studies, 12,521 participants: RR 0.79, 95% CI 0.59 to 1.04; low certainty evidence) in comparison with warfarin.
AUTHORS' CONCLUSIONS
Our findings indicate that DOAC are as likely as warfarin to prevent all strokes and systemic embolic events without increasing risk of major bleeding events among AF patients with kidney impairment. These findings should encourage physicians to prescribe DOAC in AF patients with CKD without fear of bleeding. The major limitation is that the results of this study chiefly reflect CKD stage G3. Application of the results to CKD stage G4 patients requires additional investigation. Furthermore, we could not assess CKD stage G5 patients. Future reviews should assess participants at more advanced CKD stages. Additionally, we could not conduct detailed analyses of subgroups and sensitivity analyses due to lack of data.
Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Embolism; Hemorrhage; Humans; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Rivaroxaban; Stroke; Thiazoles; Warfarin
PubMed: 29105079
DOI: 10.1002/14651858.CD011373.pub2 -
Thrombosis Research Aug 2023Idarucizumab has been approved to reverse the anticoagulant effect of dabigatran. However, there is little knowledge of the effectiveness and safety of idarucizumab in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Idarucizumab has been approved to reverse the anticoagulant effect of dabigatran. However, there is little knowledge of the effectiveness and safety of idarucizumab in daily practice.
AIMS
This systematic review and meta-analysis aims to evaluate the use, effectiveness and outcomes of idarucizumab.
METHODS
A systematic literature search was performed up to September 8th 2022. Original studies including patients prescribed idarucizumab, evaluating prescription indications, prescription appropriateness, haemostatic efficacy and/or the occurrence of adverse events were eligible. Case-reports and studies performed in patients ≤18 years or in healthy volunteers were excluded. Study selection and data extraction were performed by two independent reviewers. Pooled estimates were calculated using the random-effects model, after Freeman-Tukey double-arcsine transformation.
RESULTS
Thirty studies comprising 3602 patients were included. Idarucizumab was prescribed for bleeding (63.1 %, 95%CI 57.0 %-69.0 %), invasive procedures (30.5 %, 95%CI: 24.1 %-37.2 %), to enable thrombolysis (range: 2.0 %-27.3 %), dabigatran intoxication without bleeding (range: 3.6 %-7.0 %) or unspecified reasons (range: 0.4 %-18.8 %). Overall, 2.8 % (95%CI 0.5 %-6.2 %) of prescription indications were reported to be inappropriate upon post-hoc evaluation. Hemostatic effectiveness was achieved in 77.7 % (95%CI 66.7 %-87.2 %) and peri-procedural haemostasis was normal in 98.5 % (95%CI 86.6 %-100 %) of patients. The pooled incidences of all-cause mortality and thromboembolic events at any follow-up duration were 13.6 % (95%CI 9.6 %-17.9 %) and 2.0 % (95%CI 0.8 %-3.4 %), respectively.
CONCLUSION
Idarucizumab was mainly prescribed in the setting of bleeding. The reported hemostatic effectiveness was good, especially perioperatively, and the incidence of thromboembolic events was low. Patients with dabigatran-associated bleeding or requiring an urgent procedure nonetheless face a high mortality risk.
Topics: Humans; Dabigatran; Antithrombins; Antibodies, Monoclonal, Humanized; Hemorrhage; Thromboembolism; Hemostatics
PubMed: 37267671
DOI: 10.1016/j.thromres.2023.05.020 -
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 -
Farmacia Hospitalaria : Organo Oficial... 2012The new protease inhibitors (PIs), telaprevir and boceprevir, with peginterferon and ribavirin, have increased the response rate in patients with genotype 1 chronic... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The new protease inhibitors (PIs), telaprevir and boceprevir, with peginterferon and ribavirin, have increased the response rate in patients with genotype 1 chronic hepatitis C. Both are metabolized by CYP3A and they are CYP3A inhibitors. Furthermore, they are substrates, also telaprevir is an inhibitor, for P-glycoprotein. Our aim is to analyze the interactions between these IPs and other medications.
METHOD
We performed a systematic review in PubMed and Cochrane database and in conference abstracts of the last 2-5 years. Another search was performed in Medline to check efficacy clinical trials in phase II and III, in Micromedex database and in label information.
RESULTS
In PubMed we found two Phase I clinical trials; we did not find any article in the Cochrane database. 14 conference abstracts were selected, mainly there are phase I studies. In the free search in PubMed was located an in vitro / in vivo preclinical study which analyzed the co-administration of IPs and ritonavir. In phase II and III clinical trials, there was no mention about interactions.
CONCLUSIONS
Currently, there are pharmacokinetic Phase I studies about the interaction between PIs and representative drugs (potent inducers, potent inhibitors, high protein binding drugs, etc.), but the evidence of these interactions is contradictory. Its incorporation into the therapeutic have to take into account the possibility of complex interactions and not entirely known, about their mechanism of action, which might compromise its effectiveness or increase its toxicity.
Topics: Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Interactions; HIV Protease Inhibitors; Hepatitis C, Chronic; Humans; Oligopeptides; Proline
PubMed: 23461440
DOI: 10.7399/FH.2012.36.6.47 -
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