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American Journal of Nephrology 2024Mineralocorticoid receptor blockade could be a potential approach for the inhibition of chronic kidney disease (CKD) progression. The benefits and harms of different... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mineralocorticoid receptor blockade could be a potential approach for the inhibition of chronic kidney disease (CKD) progression. The benefits and harms of different mineralocorticoid receptor antagonists (MRAs) in CKD are inconsistent.
OBJECTIVES
The aim of the study was to summarize the benefits and harms of MRAs for CKD patients.
METHODS
We searched MEDLINE, EMBASE, and the Cochrane databases for trials assessing the effects of MRAs on non-dialysis-dependent CKD populations. Treatment and adverse effects were summarized using meta-analysis.
RESULTS
Fifty-three trials with 6 different MRAs involving 22,792 participants were included. Compared with the control group, MRAs reduced urinary albumin-to-creatinine ratio (weighted mean difference [WMD], -90.90 mg/g, 95% CI, -140.17 to -41.64 mg/g), 24-h urinary protein excretion (WMD, -0.20 g, 95% CI, -0.28 to -0.12 g), estimated glomerular filtration rate (eGFR) (WMD, -1.99 mL/min/1.73 m2, 95% CI, -3.28 to -0.70 mL/min/1.73 m2), chronic renal failure events (RR, 0.86, 95% CI, 0.79-0.93), and cardiovascular events (RR, 0.84, 95% CI, 0.77-0.92). MRAs increased the incidence of hyperkalemia (RR, 2.04, 95% CI, 1.73-2.40) and hypotension (RR, 1.80, 95% CI, 1.41-2.31). MRAs reduced the incidence of peripheral edema (RR, 0.65, 95% CI, 0.56-0.75) but not the risk of acute kidney injury (RR, 0.94, 95% CI, 0.79-1.13). Nonsteroidal MRAs (RR, 0.66, 95% CI, 0.57-0.75) but not steroidal MRAs (RR, 0.20, 95% CI, 0.02-1.68) significantly reduced the risk of peripheral edema. Steroidal MRAs (RR, 5.68, 95% CI, 1.26-25.67) but not nonsteroidal MRAs (RR, 0.52, 95% CI, 0.22-1.22) increased the risk of breast disorders.
CONCLUSIONS
In the CKD patients, MRAs, particularly in combination with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, reduced albuminuria/proteinuria, eGFR, and the incidence of chronic renal failure, cardiovascular and peripheral edema events, whereas increasing the incidence of hyperkalemia and hypotension, without the augment of acute kidney injury events. Nonsteroidal MRAs were superior in the reduction of more albuminuria with fewer peripheral edema events and without the augment of breast disorder events.
Topics: Humans; Mineralocorticoid Receptor Antagonists; Hyperkalemia; Albuminuria; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Acute Kidney Injury; Edema; Hypotension
PubMed: 37793348
DOI: 10.1159/000534366 -
The Annals of Pharmacotherapy Mar 2024To conduct a review of studies evaluating the influence of body size and weight (WT) on the pharmacokinetics (PK) of drugs recommended for heart failure (HF) treatment. (Review)
Review
OBJECTIVE
To conduct a review of studies evaluating the influence of body size and weight (WT) on the pharmacokinetics (PK) of drugs recommended for heart failure (HF) treatment.
DATA SOURCES
A systematic search of the MEDLINE (1946 to April 2023) and EMBASE (1974 to April 2023) databases was conducted for articles that focused on the impact of WT or body size on the PK of drugs of interest used in HF patients.
STUDY SELECTION AND DATA EXTRACTION
Articles written in English or French related to the aim of our study were retained for analysis.
DATA SYNTHESIS
Of 6493 articles, 20 were retained for analysis. Weight was associated with the clearance of digoxin, carvedilol, enalapril, and candesartan as well as the volume of distribution of eplerenone and bisoprolol. There was no documented direct impact of WT on the PK of furosemide, valsartan, and metoprolol, although these studies were limited or confounded by the small sample size, adjustment of PK factors by WT, or the use of the Cockroff-Gault equation for the evaluation of creatinine clearance, which includes WT.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
This review highlights and summarizes the available data on the importance of WT on the PK of HF treatment.
CONCLUSION
Considering the significant impact of WT on most HF drugs in this review, it may be important to further investigate it in the context of personalized therapy, particularly in patients presenting extreme WTs.
Topics: Humans; Heart Failure; Valsartan; Metoprolol; Carvedilol; Body Size; Adrenergic beta-Antagonists
PubMed: 37338205
DOI: 10.1177/10600280231179484 -
Environmental Research Apr 2024The Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) have effectively kept lower antibiotic-resistant bacterial (ARB) pathogen rates than many other... (Review)
Review
The Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) have effectively kept lower antibiotic-resistant bacterial (ARB) pathogen rates than many other countries. However, in recent years, these five countries have encountered a rise in ARB cases and challenges in treating infections due to the growing prevalence of ARB pathogens. Wastewater-based surveillance (WBS) is a valuable supplement to clinical methods for ARB surveillance, but there is a lack of comprehensive understanding of WBS application for ARB in the Nordic countries. This review aims to compile the latest state-of-the-art developments in WBS for ARB monitoring in the Nordic countries and compare them with clinical surveillance practices. After reviewing 1480 papers from the primary search, 54 were found relevant, and 15 additional WBS-related papers were included. Among 69 studies analyzed, 42 dedicated clinical epidemiology, while 27 focused on wastewater monitoring. The PRISMA review of the literature revealed that Nordic countries focus on four major WBS objectives of ARB: assessing ARB in the human population, identifying ARB evading wastewater treatment, quantifying removal rates, and evaluating potential ARB evolution during the treatment process. In both clinical and wastewater contexts, the most studied targets were pathogens producing carbapenemase and extended-spectrum beta-lactamase (ESBL), primarily Escherichia coli and Klebsiella spp. However, vancomycin-resistant Enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) have received more attention in clinical epidemiology than in wastewater studies, probably due to their lower detection rates in wastewater. Clinical surveillance has mostly used culturing, antibiotic susceptibility testing, and genotyping, but WBS employed PCR-based and metagenomics alongside culture-based techniques. Imported cases resulting from international travel and hospitalization abroad appear to have frequently contributed to the rise in ARB pathogen cases in these countries. The many similarities between the Nordic countries (e.g., knowledge exchange practices, antibiotic usage patterns, and the current ARB landscape) could facilitate collaborative efforts in developing and implementing WBS for ARB in population-level screening.
Topics: Humans; Wastewater; Methicillin-Resistant Staphylococcus aureus; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Drug Resistance, Microbial; beta-Lactamases; Escherichia coli; Scandinavian and Nordic Countries
PubMed: 38163547
DOI: 10.1016/j.envres.2023.118052 -
Journal of Human Hypertension May 2024Hypertension is the leading risk factor for premature death. The optimal treatment of low-renin hypertension (LRH), present in 30% of hypertensive individuals, is not... (Meta-Analysis)
Meta-Analysis
Hypertension is the leading risk factor for premature death. The optimal treatment of low-renin hypertension (LRH), present in 30% of hypertensive individuals, is not known. LRH likely reflects a state of excess salt, expanded volume and/or mineralocorticoid receptor (MR) activation. Therefore, targeted treatment with MR antagonists (MRA) may be beneficial. The objective of this systematic review was to assess the efficacy of MRA therapy in LRH. MEDLINE, Embase and Cochrane databases were searched for randomised controlled trials of adults with LRH that compared the efficacy of MRA to placebo or other antihypertensive treatments. Risk of bias was assessed using the Cochrane risk of bias tool. A meta-analysis was performed using a random-effects model to estimate the difference in blood pressure and the certainty of evidence was assessed using the GRADE approach. The protocol is registered on PROSPERO (CRD42022318763). From the 1612 records identified, 17 studies met the inclusion criteria with a total sample size of 1043 participants. Seven studies (n = 345) were assessed as having a high risk of bias. Meta-analysis indicated that MRA reduced systolic blood pressure by -6.8 mmHg (95% confidence interval -9.6 to -4.1) and -4.8 mmHg (95% confidence interval -11.9 to 2.4) compared to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) and diuretics. The certainty of the evidence was assessed as moderate and very low, respectively. The findings of this systematic review suggest that MRA is effective in lowering blood pressure in LRH and may be better than ACEi/ARB. Translation to clinical practice is limited by the uncertainty of evidence.
Topics: Humans; Mineralocorticoid Receptor Antagonists; Hypertension; Treatment Outcome; Renin; Blood Pressure; Antihypertensive Agents
PubMed: 38200100
DOI: 10.1038/s41371-023-00891-1 -
Archives of Gerontology and Geriatrics Nov 2023The risk-to-benefit ratio of cardioprotective medications in frail older adults is uncertain. The objective was to systematically review prescribing of... (Review)
Review
AIMS
The risk-to-benefit ratio of cardioprotective medications in frail older adults is uncertain. The objective was to systematically review prescribing of guideline-recommended cardioprotective medications following myocardial infarction (MI) in people who are frail.
DATA SOURCES
Ovid Medline, PubMed and Cochrane were searched from inception to October 2022 for studies that reported prescribing of one or more cardioprotective medication classes post-MI or acute coronary syndromes in people with frailty.
STUDY SELECTION
We included observational studies that reported prescribing of cardioprotective medications post-MI stratified by frailty status.
RESULTS
Overall, 16 cohort studies published from 2013 to 2022 that used seven different frailty scales were included. Prescribing of all cardioprotective medication classes following MI was lower in frail compared to non-frail people, with absolute rates of prescribing varying substantially across studies. Median prescribing in frail and non-frail people, respectively, was 88.9% (IQR 81.5-96.2) and 93.1% (IQR 92.0-98.9) for aspirin; 68.1% (IQR 61.9-91.2) and 86.7% (IQR 79.5-92.8) for P2Y12-inhibitors; 83.1% (IQR 76.9-91.3) and 94.0% (IQR 87.1-95.9) for lipid-lowering therapy; 67.9% (IQR 60.6-74.0) and 74.7% (IQR 71.3-84.5) for angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers; and 74.1% (IQR 69.2-79) and 77.6% (IQR 71.8-85.9) for beta-blockers.
CONCLUSION
People who were frail were less likely to be prescribed guideline recommended medication classes post-MI than those who were non-frail. Further research is needed into treatment benefits and risks in frail people to avoid unnecessarily withholding treatment in this high-risk population, while also minimising potential for medication related harm.
Topics: Humans; Aged; Frailty; Myocardial Infarction; Acute Coronary Syndrome; Angiotensin-Converting Enzyme Inhibitors; Risk Factors
PubMed: 37356114
DOI: 10.1016/j.archger.2023.105106 -
Alternative Therapies in Health and... Apr 2024Heart failure with preserved ejection fraction (HFpEF) is a prevalent and clinically significant condition characterized by limited treatment options. In this context,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Heart failure with preserved ejection fraction (HFpEF) is a prevalent and clinically significant condition characterized by limited treatment options. In this context, the objective of this meta-analysis is to evaluate the effectiveness of sacubitril/valsartan compared to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in managing HFpEF.
METHODS
A systematic search of relevant studies was conducted in PubMed, Embase, Web of Science, and Cochrane Library. Randomized controlled trials comparing sacubitril/valsartan to ACEIs or ARBs in HFpEF patients were included. Inclusion criteria: LVEF>45%, NYHA II-IV, Sac/Val vs ACEI/ARB, RCTs, treatment duration >3 months, sample size ≥25 per group. Exclusion criteria: Animal studies, unclear/missing data, poor quality, case studies/expert opinions.Hospitalization for heart failure and cardiovascular mortality were the primary outcomes, while the additional results included mortality from all causes, improvement of NYHA class, modifications in NT-proBNP, and with LVEF.
RESULTS
Sacubitril/valsartan substantially reduced heart failure hospitalization rates compared to ACEIs and ARBs, according to a total of six studies involving 5,201 participants (Relative Risk, 0.78; 95% CI, 0.65 to 0.85; P = .001). Nonetheless, there were no significant improvements in mortality due to cardiovascular disease (Relative Risk, 0.94; 95% CI, 0.79-1.12; P = .563). Sacubitril/valsartan did not affect total mortality from all causes significantly (Relative Risk, 0.95; 95% CI, 0.84-1.09; P = .453), but it did enhance NYHA classification (Relative Risk, 1.25; 95% CI, 1.10-1.43; P = .001). NT-proBNP levels decreased substantially (Weighted Mean Difference, -266.67; 95% CI, -525.86 to -7.47), whereas there had been little major shift in LVEF (Weighted Mean Difference, 1.49; 95% CI, -1.33 to 4.21; P = .342).
CONCLUSIONS
Sacubitril/valsartan may provide superior benefits in reducing heart failure hospitalization rates, NT-proBNP levels, and improving NYHA classification in patients with HFpEF compared to ACEIs and ARBs. Sacubitril/valsartan might be considered as a preferred treatment option for HFpEF patients due to its benefits in reducing heart failure hospitalization rates and improving symptom severity.
Topics: Humans; Valsartan; Heart Failure; Biphenyl Compounds; Aminobutyrates; Drug Combinations; Stroke Volume; Angiotensin Receptor Antagonists; Tetrazoles; Aged; Angiotensin-Converting Enzyme Inhibitors
PubMed: 37917889
DOI: No ID Found -
Reviews on Environmental Health Aug 2023Through the Mas receptor, angiotensin-(1-7) [Ang-(1-7)] has been shown to have a key role in the development of lung inflammation. This systematic review (SR) sought to... (Review)
Review
Through the Mas receptor, angiotensin-(1-7) [Ang-(1-7)] has been shown to have a key role in the development of lung inflammation. This systematic review (SR) sought to identify the relationship between lung damage brought on by exposure to cigarette smoke (CS) and the ACE2-Ang-(1-7)-Mas pathway. In this investigation, relevant keywords were used to search PubMed (MEDLINE), Scopus (Elsevier), and Institute for Scientific Information (ISI) Web of Science up to December 2022. Nine studies were chosen because they satisfied the inclusion/exclusion criteria. The majority of research concluded that exposure to CS increased the risk of lung damage. Smoking cigarettes is the main cause of COPD because it causes massive amounts of reactive oxygen and nitrogen species to enter the lungs, which stimulate the production of inflammatory cytokines like IL-1 β, IL-6, and TNF-α, as well as the invasion of inflammatory cells like neutrophils and macrophages. These findings support the renin-angiotensin system's (RAS) involvement in the pathophysiology of smoking-induced damage. Additionally, via stimulating pro-inflammatory mediators, aberrant RAS activity has been linked to lung damage. Lung inflammation's etiology has been shown to be significantly influenced by the protective known RAS arm ACE2-Ang-(1-7)-Mas. In conclusion, these are important for informing policymakers to pass legislation limiting the use of smoking and other tobacco to prevent their harmful effects.
PubMed: 37534601
DOI: 10.1515/reveh-2023-0028 -
International Journal of Cardiology Apr 2024Despite the established efficacy of vericiguat compared to placebo, uncertainties remain regarding its comparative efficacy to sacubitril/valsartan for patients with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite the established efficacy of vericiguat compared to placebo, uncertainties remain regarding its comparative efficacy to sacubitril/valsartan for patients with heart failure reduced ejection fraction (HFrEF). This study aimed to assess the relative efficacy of vericiguat and sacubitril/valsartan through a systematic review, network meta-analysis, and non-inferiority tests.
METHODS
A systematic review was conducted to identify the randomized phase 3 clinical trials involving vericiguat and sacubitril/valsartan. The hazard ratios (HRs) with 95% confidence intervals (CI) for cardiovascular death (CVD) and hospitalization due to HF (hHF) were extracted from these trials and synthesized via network meta-analysis. Non-inferiority testing of vericiguat was performed using a fixed-margin method with a predefined non-inferiority margin (1.24). Sensitivity analyses explored the impact of the time from hHF to screening.
RESULTS
Among the 1366 studies, two trials (VICTORIA and PARADIGM-HF) met the inclusion criteria. Network meta-analysis demonstrated that the HR for CVD or hHF with vericiguat did not significantly differ from that for sacubitril/valsartan (HR: 0.88, 95% CI:0.62-1.23). The upper limit of the 95% CI was less than the predefined margin of 1.24, confirming vericiguat's non-inferiority to sacubitril/valsartan. Sensitivity analyses affirmed the robustness of the base-case results.
CONCLUSION
Vericiguat exhibited a comparable risk of CVD or hHF when contrasted with sacubitril/valsartan. Importantly, in patients with HFrEF, vericiguat's efficacy was not statistically inferior to that of sacubitril/valsartan. These findings reinforce the potential of vericiguat as a viable treatment option for this patient population.
Topics: Humans; Heart Failure; Network Meta-Analysis; Tetrazoles; Stroke Volume; Valsartan; Aminobutyrates; Biphenyl Compounds; Drug Combinations; Ventricular Dysfunction, Left; Angiotensin Receptor Antagonists; Heterocyclic Compounds, 2-Ring; Pyrimidines
PubMed: 38242507
DOI: 10.1016/j.ijcard.2024.131786 -
Cardiovascular Journal of Africa Nov 2023As the impact of angiotensin receptor/neprilysin inhibitor (ARNI) on cardiac function in acute myocardial infarction (AMI) patients is unclear in clinical therapy, we...
AIM
As the impact of angiotensin receptor/neprilysin inhibitor (ARNI) on cardiac function in acute myocardial infarction (AMI) patients is unclear in clinical therapy, we conducted this research to investigate the actual effects of improving cardiac function with ARNI in AMI patients.
METHODS
Publications were checked up to June 2022. Standardised mean differences (SMD) and 95% confidence intervals (CI) were utilised for assessing the size of the effect of continuous variables. To assess the magnitude of the effect of dichotomous variables, a relative risk (RR) with 95% CI was used.
RESULTS
ARNI could improve left ventricular ejection fraction (SMD = 0.40; 95% CI: 0.23 - 0.58), while lowering left ventricular end-diastolic volume (SMD = -0.43, 95% CI: -0.78 to -0.08), left ventricular end-systolic volume (SMD = -0.39, 95% CI: -0.66 to -0.11) and left ventricular enddiastolic diameter (SMD = -0.49; 95% CI: -0.65 to -0.33). Besides, it could decrease the rates of major adverse cardiac events (RR = 0.55; 95% CI: 0.43 - 0.69) and heart failure (RR = 0.42; 95% CI: 0.31 - 0.58).
CONCLUSION
ARNI could greatly improve cardiac function in AMI patients.
PubMed: 38032681
DOI: 10.5830/CVJA-2023-028 -
International Journal of Nephrology 2024Cisplatin (CDDP) is a highly potent chemotherapy drug. But its nephrotoxicity poses a significant limitation to its use. The renin-angiotensin system (RAS) has been... (Review)
Review
Cisplatin (CDDP) is a highly potent chemotherapy drug. But its nephrotoxicity poses a significant limitation to its use. The renin-angiotensin system (RAS) has been proposed to play a role in drug-induced nephrotoxicity. This systematic review (SR) sought to identify the link between CDDP-induced nephrotoxicity and the RAS pathway. In this SR, relevant keywords were employed to explore databases such as PubMed (MEDLINE), Scopus (Elsevier), and Institute for Scientific Information (ISI) Web of Science up to October 2023. Nine studies were selected based on predefined inclusion/exclusion criteria. The findings support the involvement of the RAS in the CDDP-induced nephrotoxicity model, along with the activation of inflammatory mediators, lipid peroxidation, and changes in markers of kidney tissue damage. Furthermore, physiology and pathology of RAS-related interventions in CDDP-induced nephrotoxicity models have involved the factors such as human organic cation transporter 2 (hOCT2), organic anion transporting polypeptides 1B1 (OATP1B1) and 1B3, kallikrein-kinin system, and bradykinin receptors. CDDP-induced nephrotoxicity has been found to be substantially influenced by both classic and nonclassic RAS axes. Angiotensin II exacerbates renal damage induced by CDDP. Conversely, inhibiting the pressor arm of RAS in males mitigates this damage. However, activation of the renal vasodepressor arm of RAS exacerbates CDDP-induced nephrotoxicity in females. These findings underscore gender differences in renal function and response to RAS-related interventions in the presence of CDDP. This SR provides insights into both beneficial and adverse interventions associated with RAS in the CDDP-induced nephrotoxicity, offering valuable considerations for researchers and clinicians.
PubMed: 38799728
DOI: 10.1155/2024/1511216