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Heart & Lung : the Journal of Critical... 2024Given the ongoing COVID-19 pandemic, it is crucial to prioritize the management of underlying diseases in infected patients, with hypertension being one of the most... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Given the ongoing COVID-19 pandemic, it is crucial to prioritize the management of underlying diseases in infected patients, with hypertension being one of the most common conditions. However, there lies a complicated correlation between antihypertensive agents and COVID-19 infection.
OBJECTIVES
This study is to systematically evaluate the impact of continuing or discontinuing antihypertensive agents on mortality and infection severity in hospitalized patients with both hypertension and COVID-19.
METHODS
A systematic electronic search was conducted on PubMed, Embase, Cochrane, Web of Science, and ClinicalTrials.gov to identify relevant clinical trials published between 1948 and September 2022. Two independent reviewers assessed the quality of the included studies and extracted relevant data. The primary outcome of interest was the relationship between in-hospital mortality and administration of antihypertensive agents.
RESULTS
The meta-analysis revealed that continuous administration of antihypertensive agents, compared with discontinuation, significantly reduced in-hospital mortality among hypertension patients with COVID-19 infection [OR=0.49, 95 %CI (0.38, 0.65), p < 0.001, I=65.3 %]. Specifically, patients receiving ACEI/ARB type agents had even lower mortality rates. Meta-regression analyses were conducted to examine the impact of publication date, sample size, study design, and mean age of the patients, and the results showed that the number of participants in the included studies was the primary source of heterogeneity (p = 0.032). The findings indicated a clear association between the use of antihypertensive agents and reduced mortality in these patients.
CONCLUSION
nder the current circumstance of the sustained COVID-19 pandemic, it is recommended to continue the use of antihypertensive agents for patients with hypertension during COVID-19 infection, as it can help reduce the risk of mortality.
Topics: Humans; Antihypertensive Agents; COVID-19; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Pandemics; Hypertension
PubMed: 37826924
DOI: 10.1016/j.hrtlng.2023.10.001 -
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 -
Cureus Aug 2023Amyloid-ß (Aß) plaques and Neurofibrillary tangles are hallmarks of Alzheimer's disease (AD) pathology. Recent advances to find a cure for AD have led to the... (Review)
Review
Comparative Study of Safety and Efficacy of Angiotensin-Receptor Blockers and Anti Amyloid-ß Monoclonal Antibodies for the Treatment of Alzheimer's Disease: A Systematic Review.
Amyloid-ß (Aß) plaques and Neurofibrillary tangles are hallmarks of Alzheimer's disease (AD) pathology. Recent advances to find a cure for AD have led to the exploration of Anti-Aß monoclonal antibodies and angiotensin-receptor blockers (ARBs). The antibodies can decrease plaque formation or remove already formed plaques. ARBs increase angiotensin II (AT2) levels and decrease the effect of AT2 on the AT1 receptor (AT1R). This systematic analysis reviews evidence of monoclonal antibodies (Aducanumab, Lecanemab, Donanemab, and Solanezumab) and ARBs in managing AD. An in-depth methodical search was conducted across PubMed, Science Direct, and Mendeley. PRISMA 2020 guidelines were followed for this study. Randomized control trials for antibodies and ARBs and one retrospective cohort study were included. The comparison was made among studies that shared similar measured outcomes. Antibodies were found to be more effective than ARBs, with Aducanumab and Lecanemab being the most effective. ARBs, on the other hand, were found to be the safer choice. Further trials of longer duration and larger sample sizes are needed to explore both groups' long-term safety and efficacy.
PubMed: 37746412
DOI: 10.7759/cureus.43984 -
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 -
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 -
Exploratory Research in Clinical and... Sep 2023Hypertension has affected over 1.13 billion people worldwide in 2015 and it's one of the most preventable risk-factors for morbidity and mortality. Antihypertensives... (Review)
Review
BACKGROUND
Hypertension has affected over 1.13 billion people worldwide in 2015 and it's one of the most preventable risk-factors for morbidity and mortality. Antihypertensives significantly reduce cardiovascular risks. Several studies on antihypertensives' prescribing patterns were conducted worldwide, and guidelines were developed on hypertension management. However, no systematic reviews were conducted globally to synthesize the evidence from these studies. This review aims to evaluate antihypertensives' prescription patterns, and adherence to international guidelines for hypertension management worldwide.
METHODS
Full-text antihypertensives' prescribing patterns evaluation studies were included. Reviews, commentaries, guidelines, and editorials were excluded. Various databases were searched including PubMed, Embase, and others. Studies were limited to English only and to articles published from (01/01/2010) to (20/03/2020). Crowe Critical Appraisal Tool (CCAT) was used for quality assessment.
RESULTS
The most commonly prescribed antihypertensives as monotherapy in adult patients with no comorbidities were ACEIs/ARBs (Angiotensin converting enzyme inhibitors/Angiotensin receptor blockers), followed by CCBs (Calcium channel blockers), and BBs (Beta Blockers). Most commonly prescribed dual combinations were thiazide diuretics+ACEIs/ARBs, BBs + CCBs and CCBs+ACEIs/ARBs. Among diabetic patients, the most common agents were ACEIs/ARBs. Among patients with heart diseases, CCBs were prescribed frequently. While patients with kidney diseases, CCBs and ARBs were most prescribed. Of the 40 studies included in the review, only four studies directly assessed the prescribing patterns of antihypertensives in adherence to clinical practice guidelines. And only two studies confirmed adherence to guidelines. Furthermore, the quality of the majority of studies was moderate (50%), while 25% of articles were reported as either high or low quality.
CONCLUSION
This review revealed that there are areas for improvement for prescribing practices of antihypertensives in concordance with the latest evidence and with clinical practice guidelines.
PubMed: 37635839
DOI: 10.1016/j.rcsop.2023.100315 -
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 -
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 -
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 -
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