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Medicina (Kaunas, Lithuania) Feb 2024IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage...
IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage kidney disease (ESKD). Presently, the primary strategy for managing IgAN revolves around optimizing blood pressure and mitigating proteinuria. This is achieved through the utilization of renin-angiotensin system (RAS) inhibitors, namely, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As outlined by the KDIGO guidelines, individuals who continue to show a persistent high risk of progressive ESKD, even with comprehensive supportive care, are candidates for glucocorticoid therapy. Despite these therapies, some patients have a disease refractory to treatment, defined as individuals that present a 24 h urinary protein persistently >1 g after at least two rounds of regular steroids (methylprednisolone or prednisone) and/or immunosuppressant therapy (e.g., mycophenolate mofetil), or who do not tolerate regular steroids and/or immunosuppressant therapy. The aim of this Systematic Review is to revise the current literature, using the biomedical database PubMed, to investigate possible therapeutic strategies, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, fecal microbiota transplantation, as well as blockade of complement components.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Glomerulonephritis, IGA; Angiotensin Receptor Antagonists; Nephrologists; Antihypertensive Agents; Kidney Failure, Chronic; Steroids; Immunosuppressive Agents
PubMed: 38399561
DOI: 10.3390/medicina60020274 -
Cureus Jul 2023Recent studies have focused on treating heart failure, primarily mitigating symptoms and reducing the risk of mortality and other cardiovascular complications. A... (Review)
Review
Recent studies have focused on treating heart failure, primarily mitigating symptoms and reducing the risk of mortality and other cardiovascular complications. A promising new treatment approach involves using LCZ696, an angiotensin receptor-neprilysin inhibitor (ARNI) comprising sacubitril and valsartan. This treatment is superior to the conventional drugs enalapril or valsartan in patients diagnosed with heart failure. A systematic search was conducted on PubMed, the Cochrane Library, and Elsevier's ScienceDirect databases to identify studies comparing sacubitril/valsartan with other drugs in heart failure patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). The analyses were conducted using the random-effects model. The study's primary outcomes included all-cause mortality, death from cardiovascular causes, first hospitalization for heart failure, congestive heart failure, and changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical score. The pooled analysis showed that treatment with the sacubitril/valsartan combination was associated with a significantly decreased rate of first hospitalization for heart failure (RR: 0.86; 95% CI: 0.79, 0.98, p: 0.03; I2: 57%) and significantly increased KCCQ clinical score (WMD: 2.20; 95% CI: 0.33, 4.06, p: 0.02; I2: 100%). However, the two groups had no significant difference in all-cause mortality (RR: 0.90; 95% CI: 0.80, 1.01, p: 0.08; I2: 20%), death from cardiovascular causes (RR: 0.96; 95% CI: 0.87, 1.05, p: 0.34; I2: 0%), or congestive heart failure (RR: 0.97; 95% CI: 0.75, 1.25, p: 0.19; I2: 38%). The research findings suggest that sacubitril/valsartan (LCZ696) reduces hospitalizations due to heart failure and improves KCCQ clinical scores. This treatment also reduces the decline in renal function and side effects associated with enalapril or valsartan. Nonetheless, further high-quality randomized controlled trials with large sample sizes are needed to assess other impacts of this therapy on heart failure patients. Overall, the use of LCZ696 represents a promising new approach to the treatment of heart failure.
PubMed: 37554618
DOI: 10.7759/cureus.41566 -
Medicina (Kaunas, Lithuania) Aug 2023: Severe acute respiratory syndrome coronavirus 2 caused the coronavirus disease of 2019 (COVID-19), which rapidly became a pandemic, claiming millions of lives. Apart... (Meta-Analysis)
Meta-Analysis Review
: Severe acute respiratory syndrome coronavirus 2 caused the coronavirus disease of 2019 (COVID-19), which rapidly became a pandemic, claiming millions of lives. Apart from the main manifestations of this infection concerning the respiratory tract, such as pneumonia, there are also many manifestations from the gastrointestinal tract. Of these, bleeding from the gastrointestinal tract is a significant complication quite dangerous for life. This bleeding is divided into upper and lower, and the primary pathophysiological mechanism is the entering of the virus into the host cells through the Angiotensin-converting enzyme 2 receptors. Also, other comorbidities and the medication of corticosteroids and anticoagulants are considered to favor the occurrence of gastrointestinal bleeding (GIB). : This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the studies were searched in two different databases (Scopus and PubMed) from November 2019 until February 2023. All studies that reported GIB events among COVID-19 patients were included. : 33 studies were selected and reviewed to estimate the prevalence of GIB. A total of 134,905 patients with COVID-19 were included in these studies, and there were 1458 episodes of GIB. The prevalence of GIB, in these 33 studies, ranges from 0.47% to 19%. This range of prevalence is justified by the characteristics of the COVID-19 patients. These characteristics are the severity of COVID-19, anticoagulant and other drug treatments, the selection of only patients with gastrointestinal manifestations, etc. The pooled prevalence of gastrointestinal bleeding was estimated to be 3.05%, rising to 6.2% when only anticoagulant patients were included. : GIB in COVID-19 patients is not a rare finding, and its appropriate and immediate treatment is necessary as it can be life-threatening. The most common clinical findings are melena and hematemesis, which characterize upper GIB. Treatment can be conservative; however, endoscopic management of bleeding with embolization is deemed necessary in some cases.
Topics: Humans; COVID-19; Prevalence; Gastrointestinal Hemorrhage; Anticoagulants
PubMed: 37629790
DOI: 10.3390/medicina59081500 -
Cureus Feb 2024Renin-angiotensin-aldosterone system (RAAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are commonly... (Review)
Review
A Comparative Study of the Safety and Efficacy Between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on the Management of Hypertension: A Systematic Review.
Renin-angiotensin-aldosterone system (RAAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are commonly used in the management of hypertension. High blood pressure is a vital risk factor for cardiovascular disease. This study aims to establish any significant difference in using ACEIs and ARBs in managing hypertension. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to conduct this systematic review. We searched PubMed, MEDLINE, and ScienceDirect for articles published in the last 20 years (2003 to 2023). Our search was last done on the 27th of June, 2023. Following the initial search, 8,313 articles were found on PubMed. After screening the articles selected from the databases, 10 articles examining 1,621,445 patients were selected for the final study. Three articles were identified that compared ACEI and ARB in their capacity to lower blood pressure. Six articles compared both medications' capacity to reduce cardiovascular events and mortality. Five articles were identified that compared both classes of drugs for adverse effects. This study was made to determine whether or not there is a difference between the use of ACEIs and ARBs in the treatment of hypertension. The study showed that both ACEIs and ARBs are similar in their efficacy in lowering blood pressure. However, ACEI was revealed to be superior to ARB in reducing cardiovascular events and all-cause mortality. ARB was shown to be better tolerated by patients than ACEI.
PubMed: 38496070
DOI: 10.7759/cureus.54311 -
JID Innovations : Skin Science From... Nov 2023Acting on the renin-angiotensin-aldosterone system, angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are mechanisms of some of... (Review)
Review
Acting on the renin-angiotensin-aldosterone system, angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are mechanisms of some of the most prescribed medications in the world. In addition to their routine use for the treatment of hypertension, such agents have gained attention for their influence on the angiotensin receptor pathway in fibrotic skin disorders, including scars and keloids. To evaluate the current level of evidence supporting the use of these agents, a systematic review related to ACE-Is/ARBs and cutaneous scarring was conducted. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus from database inception through January 26, 2022. Two independent reviewers identified eligible studies for inclusion and extracted data. Data were insufficient for meta-analysis and are presented narratively. Of 461 citations identified, seven studies were included (199 patients). The studies included two randomized clinical trials, one comparative observation study, and four case reports. All the included studies reported statistically significant improvement in cutaneous scarring in patients using ACE-Is/ARBs compared with that in those treated with placebo/control using various outcome measures such as scar size and scar scales. However, much of the literature on this subject to date is limited by study design.
PubMed: 37840767
DOI: 10.1016/j.xjidi.2023.100231 -
International Journal of Molecular... Aug 2023The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical...
The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical development are addressed in this review. A systematic literature search was conducted in three electronic databases (Medline, Web of Science, Scopus) and in the ClinicalTrials.gov register from 1 January 2016 to 1 June 2023 to identify Phase II, III and IV clinical trials evaluating drugs for the treatment of PHN. A total of 18 clinical trials were selected evaluating 15 molecules with pharmacological actions on nine different molecular targets: Angiotensin Type 2 Receptor (AT2R) antagonism (olodanrigan), Voltage-Gated Calcium Channel (VGCC) α2δ subunit inhibition (crisugabalin, mirogabalin and pregabalin), Voltage-Gated Sodium Channel (VGSC) blockade (funapide and lidocaine), Cyclooxygenase-1 (COX-1) inhibition (TRK-700), Adaptor-Associated Kinase 1 (AAK1) inhibition (LX9211), Lanthionine Synthetase C-Like Protein (LANCL) activation (LAT8881), N-Methyl-D-Aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone and hydromorphone) and Nerve Growth Factor (NGF) inhibition (fulranumab). In brief, there are several drugs in advanced clinical development for treating PHN with some of them reporting promising results. AT2R antagonism, AAK1 inhibition, LANCL activation and NGF inhibition are considered first-in-class analgesics. Hopefully, these trials will result in a better clinical management of PHN.
Topics: Humans; Drugs, Investigational; Nerve Growth Factor; Neuralgia, Postherpetic; Pregabalin; Randomized Controlled Trials as Topic
PubMed: 37629168
DOI: 10.3390/ijms241612987 -
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 -
Frontiers in Pharmacology 2023To systematically assess the efficacy and safety of sacubitril/valsartan (SV) by comparison with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin...
The efficacy and safety of sacubitril/valsartan compared with ACEI/ARB in the treatment of heart failure following acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials.
To systematically assess the efficacy and safety of sacubitril/valsartan (SV) by comparison with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for the treatment of heart failure caused by acute myocardial infarction (HF-AMI) based on current randomized controlled trials (RCTs). Several electronic databases were searched up to 27 May 2023. Primary endpoints were the efficacy including the left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), N-terminal pro-B type natriuretic peptide (NT-proBNP) and 6-min walk test (6MWT) and secondary endpoints were the safety including the major adverse cardiovascular event (MACE) and adverse reaction (AE). A total of 14 RCTs were included and all patients were from China. Among included 1,991 patients, 997 patients received SVs and 994 patients received ACEIs/ARBs. The pooled results demonstrated that patients in the SV group showed significantly better efficacy representing as increased LVEF [weighted mean difference (WMD): 4.43%, 95% confidence interval (CI): 2.84%-6.02%, < 0.001] and 6MWT (WMD: 30.84 m, 95% CI: 25.65 m-36.03 m, < 0.001) and decreased LVEDD (WMD: -3.24 mm, 95% CI: -4.96 mm ∼ -1.52 mm, < 0.001) and NT-proBNP (WMD: -188.12 pg/mL, 95% CI: -246.75 pg/mL ∼ 129.49 pg/mL, < 0.001), which was also verified by subgroup analysis based on the history of percutaneous coronary intervention (PCI). Besides, the SV group showed significantly lower incidence rate of MACE [relative risk (RR): 0.60, 95% CI: 0.47-0.75, < 0.001] and patients receiving SVs in the non-PCI group also showed lower incidence of AE (RR: 0.38, 95% CI: 0.20-0.71, = 0.002). For the treatment of HF-AMI, SV is more effective and safer than ACEI/ARB based on current evidence, but more high-quality RCTs are still needed to verify above findings.
PubMed: 37601056
DOI: 10.3389/fphar.2023.1237210 -
Military Medical Research Oct 2023Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations,...
BACKGROUND
Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations, such as firefighting, law enforcement, military, and sports. A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment.
METHODS
To study regulatory processes in intense physical activity simulating real-life conditions, we performed a multi-omics analysis of three biofluids (blood plasma, urine, and saliva) collected from 11 wildland firefighters before and after a 45 min, intense exercise regimen. Omics profiles post- versus pre-exercise were compared by Student's t-test followed by pathway analysis and comparison between the different omics modalities.
RESULTS
Our multi-omics analysis identified and quantified 3835 proteins, 730 lipids and 182 metabolites combining the 3 different types of samples. The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands. The urine analysis showed a strong, concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites, reabsorption of nutrients and maintenance of fluid balance. In saliva, we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides. A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection.
CONCLUSION
This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility, suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.
Topics: Humans; Multiomics; Exercise; Cytokines
PubMed: 37853489
DOI: 10.1186/s40779-023-00477-5 -
Annals of Medicine and Surgery (2012) Oct 2023The incidence of morbidity and mortality in patients with type 2 diabetes mellitus is substantially correlated with cardiovascular disease and chronic kidney disease.... (Review)
Review
BACKGROUND AND OBJECTIVES
The incidence of morbidity and mortality in patients with type 2 diabetes mellitus is substantially correlated with cardiovascular disease and chronic kidney disease. The current guidelines recommend the use of renin-angiotensin system blockers, but recent studies probed into the effects of finerenone to mitigate the risk of cardiorenal events. This meta-analysis was performed to demonstrate the effects of finerenone on cardiorenal events, comprising cardiovascular mortality, heart failure, change in estimated glomerular filtration rate, and serum potassium levels.
METHODS
After screening with our eligibility criteria, 350 articles were identified with an initial literature search on multiple databases, including PubMed, Science Direct, and Cochrane Central. Seven randomized controlled trials with a total of 15 462 patients (=8487 in the finerenone group; =6975 in the control group) were included.
RESULTS
Patients receiving finerenone were at a reduced risk for cardiovascular mortality [HR: 0.84 (0.74, 0.95)], heart failure [OR: 0.79 (0.68, 0.92)], decrease in estimated glomerular filtration rate by 40% [OR: 0.82 (0.74, 0.91)] and by 57% [OR: 0.70 (0.59, 0.82)]; and a higher incidence of moderate hyperkalemia [OR: 2.25 (1.78, 2.84)].
CONCLUSION
Finerenone, owing to its better mineralocorticoid affinity, and a much lower risk of adverse effects, promises to be a much better alternative than other renin-angiotensin system blockers available for the treatment of chronic kidney disease patients with type 2 diabetes. Further trials should be conducted to provide more definitive evidence to assess the safety and efficacy of finerenone compared to spironolactone and eplerenone.
PubMed: 37811017
DOI: 10.1097/MS9.0000000000001180