-
Current Problems in Cardiology May 2023Heart failure is a growing global health concern with high mortality and morbidity. Beta-blockers, mineralocorticoid receptor antagonists, and... (Review)
Review
Heart failure is a growing global health concern with high mortality and morbidity. Beta-blockers, mineralocorticoid receptor antagonists, and angiotensin-converting-enzyme inhibitors are the treatments of choice for worsening clinical symptoms. In early 2021, the FDA approved a new oral soluble guanylate cyclase stimulator, Vericiguat, for the treatment of chronic heart failure. To evaluate the efficacy and safety of this approved drug, we conducted a systematic review of the available randomized controlled trials (RCTs). A literature search was conducted using PubMed, The Cochrane Library, and Clinicaltrials.gov from inception to June 6, 2022, without any language restriction. The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The quality of the included studies was checked using the Cochrane Risk-of-Bias tool. After a thorough literature search, 7 studies met our pre-defined criteria and were therefore included in this review. Our review suggests that vericiguat was better in preventing all causes of death, cardiovascular death, and hospitalizations due to heart failure irrespective of the atrial fibrillation status of the patients and was even beneficial for patients with NT-proBNP levels up to 8000 pg/ml. The safety of the vericiguat, according to our review, is not up to the standards, especially with a higher dosage of vericiguat. Despite all of this, vericiguat can be a breakthrough in the treatment of heart failure as it has great potential to improve the disease severity.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Adrenergic beta-Antagonists; Heterocyclic Compounds, 2-Ring; Heart Failure; Stroke Volume
PubMed: 36623755
DOI: 10.1016/j.cpcardiol.2023.101586 -
Medicine Dec 2017Genetic factors in the pathogenesis of cardiomyopathies have received a lot of attention during the past 2 decades. Some studies have reported that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Genetic factors in the pathogenesis of cardiomyopathies have received a lot of attention during the past 2 decades. Some studies have reported that angiotensin-converting enzyme (ACE) gene has been associated with hypertrophic cardiomyopathy (HCM). However, there have been inconsonant results among different studies. To clarify the influence of ACE on HCM, a systemic review and meta-analysis of case-control studies were performed.
METHODS
The following databases were searched to indentify related studies: PubMed database, the Embase database, the Cochrane Central Register of Controlled Trials database, China National Knowledge Information database, and Chinese Scientific and Technological Journal database. Search terms included "hypertrophic cardiomyopathy," "angiotensin converting enzyme" or "ACE," and "polymorphism or mutation."
RESULTS
Fifteen separate studies were suitable for the inclusion criterion. The selected studies contained 2972 participants, including 1047 in HCM group and 1925 controls. Pooled odds ratios (ORs) were calculated to assess the association between ACE insertion/deletion (I/D) polymorphism and HCM. Our case-control data indicated that D allele carrier is a risk allele in all genetic models: allele contrast (D vs I: OR = 1.35, 95% confidence interval [CI]: 1.10-1.65, P = .004), homozygous comparison (DD vs II: OR = 1.69; 95% CI: 1.12-2.54; P = .01), dominant model (DD + ID vs II: OR = 1.52, 95% CI: 1.15-2.02, P = .003), and recessive model (DD vs ID + II: OR = 1.34, 95% CI: 0.99-1.81, P = .03).
CONCLUSION
In summary, the current meta-analysis provided solid evidence suggesting that ACE gene I/D polymorphism was probably a genetic risk factor for HCM.
Topics: Alleles; Cardiomyopathy, Hypertrophic; Genetic Predisposition to Disease; Humans; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Risk
PubMed: 29310338
DOI: 10.1097/MD.0000000000008639 -
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 -
Neuroscience and Biobehavioral Reviews Sep 2018To explore effects of the brain renin-angiotensin system (RAS) on cognition.
OBJECTIVES
To explore effects of the brain renin-angiotensin system (RAS) on cognition.
DESIGN
Systematic review of experimental (non-human) studies assessing cognitive effects of RAS peptides angiotensin-(3-8) [Ang IV] and angiotensin-(1-7) [Ang-(1-7)] and their receptors, the Ang IV receptor (AT4R) and the Mas receptor.
RESULTS
Of 450 articles identified, 32 met inclusion criteria. Seven of 11 studies of normal animals found Ang IV had beneficial effects on tests of passive or conditioned avoidance and object recognition. In models of cognitive deficit, eight of nine studies found Ang IV and its analogs (Nle-Ang IV, dihexa, LVV-hemorphin-7) improved performance on spatial working memory and passive avoidance tasks. Two of three studies examining Ang-(1-7) found it benefited memory. Mas receptor removal was associated with reduced fear memory in one study.
CONCLUSION
Studies of cognitive impairment show salutary effects of acute administration of Ang IV and its analogs, as well as AT4R activation. Brain RAS peptides appear most effective administered intracerebroventricularly, close to the time of learning acquisition or retention testing. Ang-(1-7) shows anti-dementia qualities.
Topics: Angiotensin I; Angiotensin II; Animals; Cognition Disorders; Databases, Bibliographic; Dementia; Disease Models, Animal; Humans; Memory, Short-Term; Peptide Fragments
PubMed: 29733881
DOI: 10.1016/j.neubiorev.2018.05.005 -
European Heart Journal Jul 2022Trastuzumab and anthracyclines, often used in the treatment of breast cancer, may impair myocardial function, and reduce left ventricular ejection fraction (LVEF),... (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis of beta-blockers and renin-angiotensin system inhibitors for preventing left ventricular dysfunction due to anthracyclines or trastuzumab in patients with breast cancer.
AIMS
Trastuzumab and anthracyclines, often used in the treatment of breast cancer, may impair myocardial function, and reduce left ventricular ejection fraction (LVEF), potentially causing heart failure. Randomized controlled trials (RCTs) have evaluated the effects of beta-blockers (BBs), angiotensin receptor blockers (ARBs), and angiotensin-converting enzyme inhibitors (ACEI) on trastuzumab- and anthracycline-associated cardiotoxicity. We report a meta-analysis of these RCTs in patients with breast cancer.
METHODS AND RESULTS
The primary analysis was on the effect of BBs and ACEI/ARBs on LVEF in patients treated with either trastuzumab or anthracyclines. A secondary analysis was done investigating the effect of BBs or ACEI/ARBs on LVEF in trastuzumab and anthracycline treatments. Only RCTs were included using the search term 'ARBs, ACEIs, BBs, anthracyclines, trastuzumab, and breast cancer' in PubMed, Embase, and CENTRAL up to 31 March 2021. A meta-analysis was conducted to estimate the mean difference (MD) in LVEF between intervention and placebo groups at follow-up. A total of nine RCTs (n = 1362) were included in the analysis. All patients were women. BBs and ACEI/ARBs were shown to attenuate the decline in LVEF during trastuzumab and anthracycline treatments [MD: 2.4; 95% confidence interval (CI): 0.3-4.2 and MD: 1.5; 95% CI: -0.6 to 3.7]. Compared with placebo, LVEF was significantly higher in patients assigned to BB or ACEI/ARB on trastuzumab (MD: 2.3; 95% CI: 0.0-4.6) but not on anthracyclines (MD: 1.9; 95% CI: -0.5 to 4.2).
CONCLUSION
Both BB and ACEI/ARB therapies were associated with the preservation of LVEF during trastuzumab and anthracycline-containing regimens as compared with placebo, suggesting both to be beneficial.
Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anthracyclines; Antibiotics, Antineoplastic; Antihypertensive Agents; Breast Neoplasms; Female; Humans; Renin-Angiotensin System; Stroke Volume; Trastuzumab; Ventricular Dysfunction, Left
PubMed: 34951629
DOI: 10.1093/eurheartj/ehab843 -
Protein and Peptide Letters 2020Migraine is a common neurologic condition marked by recurrent episodes of headache. Its pathophysiology is highly complex involving neuronal, inflammatory and vascular...
Migraine is a common neurologic condition marked by recurrent episodes of headache. Its pathophysiology is highly complex involving neuronal, inflammatory and vascular mechanisms. The Renin-Angiotensin System (RAS) can modulate all these mechanism, being a potential pharmacological target for migraine treatment. We carried out a systematic review of the studies evaluating the involvement of RAS in patients with migraine. There is evidence from genetic studies exploring the relation between migraine and RAS-related genes and from clinical trials evaluating the efficacy of Angiotensin II Type 1 (AT1) receptor antagonists and angiotensin converting enzyme inhibitors in migraine prophylaxis. RAS seems to play a role in the pathophysiology of migraine, but more direct evidence is still missing.
Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Genetic Predisposition to Disease; Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Treatment Outcome
PubMed: 31995000
DOI: 10.2174/0929866527666200129160136 -
Giornale Italiano Di Dermatologia E... Apr 2020Treatment with antihypertensive drugs may be associated with different dermatological adverse reactions.
INTRODUCTION
Treatment with antihypertensive drugs may be associated with different dermatological adverse reactions.
EVIDENCE ACQUISITION
We systematically reviewed the literature available on the MEDLINE (PubMED) databases, up to July 2018. We searched for the terms "calcium-channel blockers" or "angiotensin-converting enzyme inhibitors" or "angiotensin II receptors blockers" or "diuretics" or "beta blockers" AND "dermatological effects" or "skin disease."
EVIDENCE SYNTHESIS
The most important cutaneous events occurring during treatment with calcium-channel blockers are represented by pedal edema and photosensitivity with consequent increased risk of skin cancer. Moreover, other adverse reactions are eczematous and psoriasiform dermatitis, subacute cutaneous lupus erythematosus, and rarely toxic epidermal necrolysis. In patients taking angiotensin-converting enzyme inhibitors or angiotensin II receptors blockers, angioedema, psoriasis and pemphigus can be exacerbated. Furthermore, some authors associated the use of these medications with the onset of skin neoplasms. As for diuretics, the most relevant cutaneous reactions are represented by subacute cutaneous lupus erythematosus and leukocytoclastic vasculitis. Photosensitivity is another important event related to diuretics use. Eventually, itching is often related to the use of thiazides, particularly in elderly patients. With regards to beta blockers, we should remember a significant association with psoriasis, lichen planus, subacute cutaneous lupus erythematosus, and an increased risk of skin cancer.
CONCLUSIONS
During antihypertensive treatment, several dermatological reactions may occur. Clinicians should inform their patients of the increased risk of cutaneous lesions associated with the use of these drugs, and perform periodic examination of the skin.
Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Drug Eruptions; Humans
PubMed: 31195782
DOI: 10.23736/S0392-0488.19.06360-0 -
Medwave Mar 2021This living systematic review aims to provide a timely, rigorous, and continuously updated summary of the evidence available on the role of angiotensin-converting enzyme... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This living systematic review aims to provide a timely, rigorous, and continuously updated summary of the evidence available on the role of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) in the treatment of patients with COVID-19.
DATA SOURCES
We conducted searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralized repository in L·OVE (Living OVerview of Evidence), which retrieves articles from multiple sources such as PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, among other pre-print and protocols repositories. In response to the COVID-19 emergency, L·OVE (Living OVerview of Evidence) was adapted to expand the range of evidence and customized to group all COVID-19 evidence in one place on a daily search basis. The search covered a period of time up to July 31, 2020.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES AND METHODS
We adapted an already published standard protocol for multiple parallel living systematic reviews to this question's specificities. We included randomized trials evaluating the effect of either suspension or indication of angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers as monotherapy, or in combination versus placebo or no treatment in patients with COVID-19. We searched for randomized trials evaluating the effect of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers versus placebo or no treatment in patients with COVID-19. Two reviewers independently screened each study for eligibility, extracted data, and assessed the risk of bias. We pooled the results using meta-analysis and applied the GRADE system to assess the certainty of the evidence for each outcome. We will resubmit results every time the conclusions change or whenever there are substantial updates.
RESULTS
We screened 772 records, but none was considered for eligibility. We identified 55 ongoing studies, including 41 randomized trials evaluating angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers for patients with COVID-19.
CONCLUSIONS
We did not find a randomized clinical trial meeting our inclusion criteria, and hence there is no evidence for supporting the role of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in the treatment of patients with COVID-19. A substantial number of ongoing studies would provide valuable evidence to inform researchers and decision-makers in the near future.
PROSPERO REGISTRATION NUMBER
CRD42020182495.
PROTOCOL PREPRINT DOI
10.31219/osf.io/vp9nj.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Humans; Randomized Controlled Trials as Topic; Research Design; COVID-19 Drug Treatment
PubMed: 33830976
DOI: 10.5867/medwave.2021.02.8105 -
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 -
European Journal of Medical Research Feb 2022To determine the effect of polymorphisms and mutations in angiotensin-converting enzyme 2 (ACE2) and Type 2 transmembrane serine proteases (TMPRSS2) genes on...
OBJECTIVE
To determine the effect of polymorphisms and mutations in angiotensin-converting enzyme 2 (ACE2) and Type 2 transmembrane serine proteases (TMPRSS2) genes on susceptibility to corona virus disease 2019 (COVID-19) and patient prognosis.
INTRODUCTION
From December 2019 to the current time, an outbreak of epidemic of COVID-19, characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has occurred around the world. It is now clear that SARS-CoV-2 binds to human ACE2 receptors, with expression of these receptors correlated with the rate of SARS-CoV-2 infection and mortality. Polymorphisms in individual patient factors, such as ACE2 and TMPRSS2 genes have been linked with an increase in negative outcomes, although evidence to affirm remains debatable.
METHODS
Here, we performed a systematic review, based on guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, with the aim of assessing whether polymorphisms in ACE2 and TMPRSS2 genes affect the COVID-19 condition. We extensively searched PubMed, MEDLINE, Embase, the Cochrane Library, and Web of Science databases, for relevant articles and reports published in English between December 2019 and December 2021.
RESULTS
A total of 495 full-text articles were downloaded, of which 185 were excluded after preliminary examination as they were duplicates. Finally, 310 articles were evaluated, by reading their titles and abstracts, and 208 of them eliminated based on our selection criteria. Finally, 33 articles met our inclusion criteria and were included in the final assessment. Genetic data from 33,923 patients with COVID-19 drawn from the general population and deriving from over 160 regions and 50 countries, as well as approximately 560,000 samples from global-public genetic databases, were included in our analysis. Ultimately, we identified 10 SNPs and 21 mutations in the ACE2 gene, along with 13 SNPs and 12 variants in the TMPRSS2 gene, which may be associated with COVID-19.
CONCLUSIONS
ACE2 and TMPRSS2 play vital roles in the onset, development, and prognosis of SARS-CoV-2 infection, and have both been strongly associated with vulnerability, intensity, and the clinical result of COVID-19. Overall, these genetic factors may have potential for future development of personalized drugs and vaccines against COVID-19.
TRIAL REGISTRATION
CRD42021239400 in PROSPERO 2021.
Topics: Angiotensin-Converting Enzyme 2; COVID-19; Genetic Predisposition to Disease; Humans; Mutation; Polymorphism, Single Nucleotide; SARS-CoV-2; Serine Endopeptidases
PubMed: 35193695
DOI: 10.1186/s40001-022-00647-6