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Diabetes, Obesity & Metabolism Feb 2024The results from the SUSTAIN-6 trial generated some uncertainty regarding the association between incretin-based drugs [dipeptidyl peptidase-4 (DPP-4) inhibitors and... (Meta-Analysis)
Meta-Analysis
AIM
The results from the SUSTAIN-6 trial generated some uncertainty regarding the association between incretin-based drugs [dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs)] and the risk of diabetic retinopathy. Our objective was to synthesize the available evidence from observational studies regarding the use of incretin-based drugs and the risk of diabetic retinopathy among individuals with type 2 diabetes.
MATERIALS AND METHODS
We systemically searched Cochrane Library, Embase and Medline to identify observational studies of interest. Risk of bias was assessed using the ROBINS-I tool. Data from included studies were pooled using the DerSimonian and Laird random-effect model with the Hartung-Knapp extension.
RESULTS
We included 14 studies in the systematic review, with 10 examining DPP-4 inhibitors and seven examining GLP-1 RAs. Nine studies investigated incident diabetic retinopathy, six investigated diabetic retinopathy progression and two investigated both outcomes. Seven studies were at moderate risk of bias, four at serious risk of bias and three at critical risk of bias. Data pooled across studies showed no association between the use of DPP-4 inhibitors (risk ratio: 0.98, 95% confidence interval: 0.83, 1.17) or GLP-1 RAs (risk ratio: 0.87, 95% confidence interval: 0.56, 1.34) and the risk of diabetic retinopathy.
CONCLUSION
This study suggests that the use of incretin-based drugs is not associated with the risk of diabetic retinopathy among individuals with type 2 diabetes. However, these findings should be interpreted with caution considering the limited quality of some of the available evidence.
Topics: Humans; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Hypoglycemic Agents; Incretins; Observational Studies as Topic
PubMed: 38031234
DOI: 10.1111/dom.15367 -
Nephrology, Dialysis, Transplantation :... Oct 2023Although renin-angiotensin-aldosterone system (RAAS) blockers have been considered the primary treatment for patients with Alport syndrome (AS) for a decade, there is no... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although renin-angiotensin-aldosterone system (RAAS) blockers have been considered the primary treatment for patients with Alport syndrome (AS) for a decade, there is no comprehensive review with evidence-based analysis evaluating the effectiveness of RAAS blockers in AS.
METHODS
A systematic review and meta-analysis was performed of published studies that compared outcomes related to disease progression between patients with AS receiving RAAS blockers with those taking non-RAAS treatment. Outcomes were meta-analyzed using the random effects models. Cochrane risk-of-bias, Newcastle-Ottawa Scale and Grading of Recommendations Assessment, Development and Evaluation methodology (GRADE) assessment determined the certainty of evidence.
RESULTS
A total of eight studies (1182 patients) were included in the analysis. Overall, the risk of bias was low to moderate. Compared with non-RAAS treatment, RAAS blockers could reduce the rate of progression to end-stage kidney disease (ESKD) [four studies; hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.24-0.45; moderate certainty evidence]. After stratified by genetic types, a similar benefit was detected: male X-linked AS (XLAS) (HR 0.32, 95% CI 0.22-0.48), autosomal recessive AS (HR 0.25, 95% CI 0.10-0.62), female XLAS and autosomal dominant AS (HR 0.40, 95% CI 0.21-0.75). In addition, RAAS blockers showed a clear gradient of benefit depending on the stage of disease at the initiation of treatment.
CONCLUSION
This meta-analysis suggested that RAAS blockers could be considered as a specific therapy to delay of ESKD for AS with any genetic type, especially at the early stage of the disease, and every further more-effective therapy would be advised to be applied on top of this standard of care.
Topics: Humans; Male; Female; Renin-Angiotensin System; Angiotensin-Converting Enzyme Inhibitors; Nephritis, Hereditary; Kidney Failure, Chronic
PubMed: 37218713
DOI: 10.1093/ndt/gfad105 -
Journal of the Formosan Medical... May 2024The introduction of non-vitamin K antagonist oral anticoagulants (NOACs), with a non-inferior or superior clinical efficacy profile compared to vitamin K antagonists... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
The introduction of non-vitamin K antagonist oral anticoagulants (NOACs), with a non-inferior or superior clinical efficacy profile compared to vitamin K antagonists (VKAs), has significantly improved the safety profile and treatment adherence of patients with non-valvular atrial fibrillation (AF). However, few studies have compared the effectiveness and safety of NOACs. Therefore, we conducted this systematic review and network meta-analysis to compare the safety and clinical effectiveness of NOACs and VKAs in patients with non-valvular AF.
METHODS
An online bibliographic search was conducted to retrieve real-world evidence studies published between January 2019 and June 2022.
RESULTS
Dabigatran was associated with lower risks of major bleeding, ischemic stroke, and intracranial hemorrhage than warfarin. Among the NOACs, only dabigatran had a lower risk of all-cause mortality than warfarin. Dabigatran was also associated with lower risks of major bleeding and intracranial hemorrhage than rivaroxaban.
CONCLUSION
Our meta-analysis confirms that dabigatran's real-world safety and clinical effectiveness align with the results of pivotal clinical trials.
Topics: Humans; Atrial Fibrillation; Warfarin; Anticoagulants; Network Meta-Analysis; Dabigatran; Administration, Oral; Hemorrhage; Stroke; Rivaroxaban; Vitamin K
PubMed: 37996330
DOI: 10.1016/j.jfma.2023.10.014 -
Injury Dec 2023Venous thromboembolism (VTE) is a major complication of trauma. Currently, there are few studies summarising the evidence for prophylaxis in trauma settings. This review... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Venous thromboembolism (VTE) is a major complication of trauma. Currently, there are few studies summarising the evidence for prophylaxis in trauma settings. This review provides evidence for the use of VTE prophylactic interventions in trauma patients to produce evidence-based guidelines.
METHODS
A PRISMA-compliant review was conducted from Sep 2021 to June 2023, using Embase, Medline and Google Scholar. The inclusion criteria were: randomized-controlled trials (RCTs) in English published after 2000 of adult trauma patients comparing VTE prophylaxis interventions, with a sample size higher than 20. The network analysis was conducted using RStudio. The results of the pairwise comparisons were presented in the form of a league table. The quality of evidence and heterogeneity sensitivity were assessed. The primary outcome focused on venous thromboembolism (VTE), and examined deep vein thrombosis (DVT) and pulmonary embolism (PE) as separate entities. The secondary outcomes included assessments of bleeding and mortality. PROSPERO registration: CRD42021266393.
RESULTS
Of the 7,948 search results, 23 studies with a total of 21,312 participants fulfilled screening criteria, which included orthopaedic, spine, solid organ, brain, spinal cord, and multi-region trauma. Of the eight papers comparing chemical prophylaxis medications in patients with hip or lower limb injuries, fondaparinux and enoxaparin were found to be significantly superior to placebo in respect of prevention of DVT, with no increased risk of bleeding. Regarding mechanical prophylaxis, meta-analysis of two studies of inferior vena cava filters failed to provide significant benefits to major trauma patients.
CONCLUSION
Enoxaparin and fondaparinux are safe and effective options for VTE prevention in trauma patients, with fondaparinux being a cheaper and easier administration option between the two. Inconclusive results were found in mechanical prophylaxis, requiring more larger-scale RCTs.
Topics: Adult; Humans; Venous Thromboembolism; Enoxaparin; Fondaparinux; Network Meta-Analysis; Anticoagulants; Pulmonary Embolism; Hemorrhage; Multiple Trauma
PubMed: 37865011
DOI: 10.1016/j.injury.2023.111078 -
The Cochrane Database of Systematic... Feb 2024Variation in blood pressure levels display circadian rhythms. Complete 24-hour blood pressure control is the primary goal of antihypertensive treatment and reducing... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Variation in blood pressure levels display circadian rhythms. Complete 24-hour blood pressure control is the primary goal of antihypertensive treatment and reducing adverse cardiovascular outcomes is the ultimate aim. This is an update of the review first published in 2011.
OBJECTIVES
To evaluate the effectiveness of administration-time-related effects of once-daily evening versus conventional morning dosing antihypertensive drug therapy regimens on all-cause mortality, cardiovascular mortality and morbidity, total adverse events, withdrawals from treatment due to adverse effects, and reduction of systolic and diastolic blood pressure in people with primary hypertension.
SEARCH METHODS
We searched the Cochrane Hypertension Specialised Register via Cochrane Register of Studies (17 June 2022), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6, 2022); MEDLINE, MEDLINE In-Process and MEDLINE Epub Ahead of Print (1 June 2022); Embase (1 June 2022); ClinicalTrials.gov (2 June 2022); Chinese Biomedical Literature Database (CBLD) (1978 to 2009); Chinese VIP (2009 to 7 August 2022); Chinese WANFANG DATA (2009 to 4 August 2022); China Academic Journal Network Publishing Database (CAJD) (2009 to 6 August 2022); Epistemonikos (3 September 2022) and the reference lists of relevant articles. We applied no language restrictions.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing the administration-time-related effects of evening with morning dosing monotherapy regimens in people with primary hypertension. We excluded people with known secondary hypertension, shift workers or people with white coat hypertension.
DATA COLLECTION AND ANALYSIS
Two to four review authors independently extracted data and assessed trial quality. We resolved disagreements by discussion or with another review author. We performed data synthesis and analyses using Review Manager Web for all-cause mortality, cardiovascular mortality and morbidity, serious adverse events, overall adverse events, withdrawals due to adverse events, change in 24-hour blood pressure and change in morning blood pressure. We assessed the certainty of the evidence using GRADE. We conducted random-effects meta-analysis, fixed-effect meta-analysis, subgroup analysis and sensitivity analysis.
MAIN RESULTS
We included 27 RCTs in this updated review, of which two RCTs were excluded from the meta-analyses for lack of data and number of groups not reported. The quantitative analysis included 25 RCTs with 3016 participants with primary hypertension. RCTs used angiotensin-converting enzyme inhibitors (six trials), calcium channel blockers (nine trials), angiotensin II receptor blockers (seven trials), diuretics (two trials), α-blockers (one trial), and β-blockers (one trial). Fifteen trials were parallel designed, and 10 trials were cross-over designed. Most participants were white, and only two RCTs were conducted in Asia (China) and one in Africa (South Africa). All trials excluded people with risk factors of myocardial infarction and strokes. Most trials had high risk or unclear risk of bias in at least two of several key criteria, which was most prominent in allocation concealment (selection bias) and selective reporting (reporting bias). Meta-analysis showed significant heterogeneity across trials. No RCTs reported on cardiovascular mortality and cardiovascular morbidity. There may be little to no differences in all-cause mortality (after 26 weeks of active treatment: RR 0.49, 95% CI 0.04 to 5.42; RD 0, 95% CI -0.01 to 0.01; very low-certainty evidence), serious adverse events (after 8 to 26 weeks of active treatment: RR 1.17, 95% CI 0.53 to 2.57; RD 0, 95% CI -0.02 to 0.03; very low-certainty evidence), overall adverse events (after 6 to 26 weeks of active treatment: RR 0.89, 95% CI 0.67 to 1.20; I² = 37%; RD -0.02, 95% CI -0.07 to 0.02; I² = 38%; very low-certainty evidence) and withdrawals due to adverse events (after 6 to 26 weeks active treatment: RR 0.76, 95% CI 0.47 to 1.23; I² = 0%; RD -0.01, 95% CI -0.03 to 0; I² = 0%; very low-certainty evidence), but the evidence was very uncertain.
AUTHORS' CONCLUSIONS
Due to the very limited data and the defects of the trials' designs, this systematic review did not find adequate evidence to determine which time dosing drug therapy regimen has more beneficial effects on cardiovascular outcomes or adverse events. We have very little confidence in the evidence showing that evening dosing of antihypertensive drugs is no more or less effective than morning administration to lower 24-hour blood pressure. The conclusions should not be assumed to apply to people receiving multiple antihypertensive drug regimens.
Topics: Humans; Antihypertensive Agents; Hypertension; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Essential Hypertension
PubMed: 38353289
DOI: 10.1002/14651858.CD004184.pub3 -
Thrombosis Research Nov 2023Optimal anticoagulation in patients with end-stage renal disease ESRD is a matter of debate since these patients are not included in randomized controlled trials (RCTs).... (Meta-Analysis)
Meta-Analysis
Apixaban reduces the risk of major and clinically relevant non-major bleeding compared to warfarin in patients with end stage renal disease; a systematic review and meta-analysis of ten studies.
UNLABELLED
Optimal anticoagulation in patients with end-stage renal disease ESRD is a matter of debate since these patients are not included in randomized controlled trials (RCTs). Evolving data are in favor of apixaban compared to warfarin.
METHODS
We extracted data from 2 RCTs, 5 retrospective cohort studies and 3 large data-based studies. Both dosing regimens of apixaban, standard or reduced, were accepted. In most studies characteristics of patients were balanced between arms. Patients with either atrial fibrillation (AF) or venous thromboembolism (VTE) were included. Quality of studies was graded as high and the funnel plot did not detect any publication bias. In total we analyzed the outcome of 6693 ESRD patients treated with apixaban and 19,836 treated with warfarin. Our analysis was performed by using the random effects model. We report our data as Risk Ratio (RR) and associated 95 % confidence interval values (95 %, CI).
RESULTS
The RR (95 % CI) of major bleeding was 0.69 (0.57-0.84) p = 0.0002 in favor of apixaban vs warfarin with heterogeneity to be statistically significant I 63% p = 0.004. Meta-regression analysis with year of publication as moderator shows in bubble plotting that studies published earlier than 2018 were plotted as outliers. The RR (95 % CI) of clinically relevant non-major bleeding (CRNMB) was 0.74 (0.64-0.87) p = 0.0002 favoring again apixaban. Standard apixaban dose over reduced dose is less hemorrhagic compared to warfarin. Overall, in our study the risk of thrombosis in both arms was statistically non-different.
CONCLUSIONS
In our study we observed less hemorrhagic events with apixaban in ESRD patients compared to warfarin.
Topics: Humans; Warfarin; Anticoagulants; Hemorrhage; Pyridones; Kidney Failure, Chronic; Atrial Fibrillation; Venous Thromboembolism; Randomized Controlled Trials as Topic
PubMed: 37748234
DOI: 10.1016/j.thromres.2023.09.005 -
Diabetes, Obesity & Metabolism Jul 2024To conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on inflammatory biomarkers. (Meta-Analysis)
Meta-Analysis
AIMS
To conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on inflammatory biomarkers.
METHODS
Medline, Embase and the Cochrane Library were searched for RCTs investigating the effect of SGLT2 inhibitors on inflammatory biomarkers, adipokine profiles and insulin sensitivity.
RESULTS
Thirty-eight RCTs were included (14 967 participants, 63.3% male, mean age 62 ± 8.6 years) with a median (interquartile range) follow-up of 16 (12-24) weeks. Meta-analysis showed that SGLT2 inhibitors significantly improved adiponectin, interleukin-6, tumour necrosis factor receptor-1 (vs. placebo alone: standardized mean difference [SMD] 0.34 [95% confidence interval {CI} 0.23, 0.45], mean difference [MD] -0.85 pg/mL [95% CI -1.32, -0.38], SMD -0.13 [95% CI -0.20, -0.06], respectively), leptin and homeostatic model assessment of insulin resistance index (vs.
CONTROL
SMD -0.20 [95% CI -0.33, -0.07], MD -0.83 [95% CI -1.32, -0.33], respectively). There were no significant changes in C-reactive protein (CRP), tumour necrosis factor-α, plasminogen activator inhibitor-1, fibroblast growth factor-21 or monocyte chemoattractant protein-1.
CONCLUSIONS
Our analysis shows that SGLT2 inhibitors likely improve adipokine biomarkers and insulin sensitivity, but there is little evidence that SGLT2 inhibitors improve other inflammatory biomarkers including CRP.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Randomized Controlled Trials as Topic; Biomarkers; Diabetes Mellitus, Type 2; Male; Inflammation; Middle Aged; Female; Insulin Resistance; Aged; C-Reactive Protein; Adiponectin; Plasminogen Activator Inhibitor 1; Interleukin-6; Leptin; Adipokines
PubMed: 38602398
DOI: 10.1111/dom.15586 -
Alimentary Pharmacology & Therapeutics Feb 2024Although enteropathy due to angiotensin II receptor blockers (ARBs) has been known for over 10 years, clinicians' awareness of this condition is still low. (Review)
Review
BACKGROUND
Although enteropathy due to angiotensin II receptor blockers (ARBs) has been known for over 10 years, clinicians' awareness of this condition is still low.
AIMS
To systematically review the literature about clinical phenotypes, distribution of mucosal changes throughout the gastrointestinal tract and prognosis of enteropathy due to ARBs.
METHODS
According to PRISMA guidelines, we searched PubMed and Embase for relevant articles up to November 6, 2023. We included full-text papers, letters, case reports and case series describing enteropathy due to ARBs. Patients were classified into subgroups based on endoscopic and histological findings of different regions of the gastrointestinal tract. The protocol was registered with Open Science Framework (https://doi.org/10.17605/OSF.IO/TK67C).
RESULTS
We included 94 articles reporting 183 cases (101 female, mean age at diagnosis 69 ± 10 years). The clinical picture at diagnosis was characterised by severe diarrhoea (97%) and weight loss (84%, median -13 kg), leading to hospital admission in 167 (95%) patients. Olmesartan (90%) was most frequently implicated. Villous atrophy (VA) was reported in 164/183 (89%) patients. One hundred and nine had only VA, 12 had pan-gastrointestinal involvement, 23 had VA and gastric involvement and 19 had VA and colon involvement (predominantly microscopic colitis). Outcomes were reported for 178/183 (97%) patients, who all recovered clinically on ARBs withdrawal. Histological recovery occurred in all 96 patients with VA at baseline who underwent follow-up duodenal biopsy.
CONCLUSIONS
Enteropathy due to ARBs is characterised by severe malabsorption often requiring hospital admission and can involve the entire gastrointestinal tract. Clinician awareness can lead to prompt diagnosis and excellent prognosis.
Topics: Aged; Female; Humans; Middle Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Intestinal Diseases; Prognosis; Tetrazoles
PubMed: 38185985
DOI: 10.1111/apt.17855 -
Seminars in Thrombosis and Hemostasis Oct 2023Although intravenous (IV) direct thrombin inhibitors (DTI) have gained interest in pediatric extracorporeal membrane oxygenation (ECMO), dosing and safety information is...
Although intravenous (IV) direct thrombin inhibitors (DTI) have gained interest in pediatric extracorporeal membrane oxygenation (ECMO), dosing and safety information is limited. The objective of this systematic review was to characterize DTI types, dosing, monitoring, and outcomes (bleeding and thromboembolic) in pediatric ECMO patients managed with IV DTIs. We conducted searches of MEDLINE (Ovid) and Embase (Elsevier) from inception through December 2022. Case reports, retrospective studies, and prospective studies providing per-patients or summary data for patient(s) <18 years of age receiving IV DTI for ECMO anticoagulation were included. Study selection and data extraction were conducted independently by two reviewers. A total of 28 studies: 14 case reports, 13 retrospective studies, and 1 prospective study were included, totaling 329 patients. Bivalirudin was utilized in 318 (96.7%), argatroban in 9 (2.7%), and lepirudin in 2 (0.6%) patients. Infusion dosing included: bivalirudin 0.14 ± 0.37 mg/kg/h, argatroban 0.69 ± 0.73 µg/kg/min, lepirudin 0.14 ± 0.02 mg/kg/h. Laboratory monitoring tests utilized were the activated clotting time, activated partial thromboplastin time (aPTT), diluted thrombin time, and thromboelastography measures. The aPTT was utilized in most patients (95%). Thromboembolism, bleeding, or death were observed in 17%, 17%, and 23% of bivalirudin, argatroban, and lepirudin patients, respectively. Bivalirudin appears to be the most frequently used DTI in pediatric ECMO. Dosing and laboratory monitoring varied, and bleeding and thromboembolic events were reported in 17% of patients. Prospective studies are warranted to establish dosing, monitoring, safety, and efficacy of bivalirudin and other IV DTI in pediatric ECMO.
Topics: Humans; Child; Antithrombins; Extracorporeal Membrane Oxygenation; Prospective Studies; Retrospective Studies
PubMed: 37643746
DOI: 10.1055/s-0043-1772838 -
European Heart Journal. Cardiovascular... Jan 2024Randomized controlled trials (RCTs) have assessed the effects of renin-angiotensin system (RAS) blockers in adults with coronavirus disease 2019 (COVID-19). This... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Randomized controlled trials (RCTs) have assessed the effects of renin-angiotensin system (RAS) blockers in adults with coronavirus disease 2019 (COVID-19). This meta-analysis provides estimates of the safety and efficacy of treatment with (vs. without) RAS blockers from these trials.
METHODS
PubMed, Web of Science, and ClinicalTrials.gov were searched (1 March-12 April 2023). Event/patient numbers were extracted, comparing angiotensin-converting enzyme (ACE) inhibitor/angiotensin-receptor blocker (ARB) treatment with no treatment, for the outcomes: intensive care unit (ICU) admission, mechanical ventilation, vasopressor use, acute kidney injury (AKI), renal replacement therapy (RRT), acute myocardial infarction, stroke/transient ischaemic attack, heart failure, thromboembolic events, and all-cause death. Fixed-effects meta-analysis estimates were pooled.
RESULTS
Sixteen RCTs including 3492 patients were analysed. Compared with discontinuation of RAS blockers, continuation was not associated with increased risk of ICU [risk ratio (RR) 0.96, 0.66-1.41], ventilation (RR 0.77, 0.55-1.09), vasopressors (RR 0.92, 0.58-1.44), AKI (RR 1.01, 0.40-2.56), RRT (RR 1.01, 0.46-2.21), or thromboembolic events (RR 1.07, 0.36-3.19). RAS blocker initiation was not associated with increased risk of ICU (RR 0.71, 0.47-1.08), ventilation (RR 1.12, 0.91-1.38), AKI (RR 1.28, 0.89-1.86), RRT (RR 1.66, 0.89-3.12), or thromboembolic events (RR 1.20, 0.06-23.70), although vasopressor use increased (RR 1.27, 1.02-1.57). The RR for all-cause death in the continuation/discontinuation trials was 1.24 (0.80-1.92), and 1.22 (0.96-1.55) in the initiation trials. In patients with severe/critical COVID-19, RAS blocker initiation increased the risk of all-cause death (RR 1.31, 1.01-1.72).
CONCLUSION
ACE inhibitors and ARBs may be continued in non-severe COVID-19 infection, where indicated. Conversely, initiation of RAS blockers may be harmful in critically ill patients.PROSPERO registration number: CRD42023408926.
Topics: Adult; Humans; Acute Kidney Injury; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; COVID-19; Randomized Controlled Trials as Topic; Renin-Angiotensin System
PubMed: 37740450
DOI: 10.1093/ehjcvp/pvad067