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Background: Data about the safety of ACEI/ARB use in early (<3 months) posttransplant period are restricted and remain controversial. Methods: This systematic review and meta-analysis included searches of PubMed, Embase and CENTRAL from inception to 31 November 2023, for studies to compare the safety (transplant outcomes and postoperative complications) of ACEI/ARB with non-ACEI/ARB (other antihypertensive medications) initiation in early post kidney transplant period. Results: Of 1,247 citations identified, 13 eligible studies involving 1919 patients were enrolled for analyses. In short- or long-term observations, there were no differences on pooled serum creatinine between ACEI/ARB and non-ACEI/ARB groups whether initiated within 1 or 1–3 months posttransplant, however, initiation of ACEI/ARB within the first month posttransplant had an advantage effect on the mean creatinine clearance. Early initiation of ACEI/ARB posttransplant reduced the risks of patient death (RR 0.60, p = 0.009) and graft loss (RR 0.54, p = 0.0002). For postoperative complications, there were no significant differences in acute rejection risk (RR 0.87, p = 0.58), delayed graft function risk (RR 1.00, p = 0.93), hemoglobin level (MD -0.32 mg/Dl, p = 0.46) or urinary protein excretion (MD -0.10 g/24 h, p = 0.16) between two groups. However, the ACEI/ARB group had higher incidence of hyperkalemia (RR 2.43, p = 0.02). Conclusion: Early initiation of ACEI/ARB within 3 months posttransplant proved to be basically safe and has renal function recovery benefits, however, hyperkalemia needs to be noted. [ABSTRACT FROM AUTHOR]

Whether angiotensin II blockade is an effective medical treatment for abdominal aortic aneurysms (AAAs) has not been established. This systematic review and meta-analysis aimed to determine the association between angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) prescription and AAA growth and events. MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library databases were searched from their inception to 4 January 2024, with no language restrictions. The five databases were searched for randomised controlled trials (RCTs) and observational studies reporting the association between ACEi or ARB prescription and AAA growth, repair, or rupture. The primary outcome was AAA growth, with secondary outcomes of AAA rupture, AAA repair, and AAA related events (rupture and repair combined). Risk of bias was assessed using the Risk of Bias 2 tool for RCTs and with a modified Newcastle–Ottawa scale for observational studies. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Random effects models were used for meta-analyses. Eleven studies (two RCTs, eight observational studies, and one meta-analysis of individual patient data from seven populations) involving 58 022 patients were included. ACEi prescription was not associated with a statistically significant reduction in AAA growth (standard mean difference 0.01 mm/year, 95% confidence interval [CI] –0.26 – 0.28; p =.93; I 2 = 98%) or AAA repair (odds ratio [OR] 0.73, 95% CI 0.50 – 1.09; p =.65; I 2 = 61%), but was associated with a statistically significantly lower risk of AAA rupture (OR 0.87, 95% CI 0.81 – 0.93; p <.001; I 2 = 26%) and AAA related events (OR 0.82, 95% CI 0.72 – 0.95; p =.006; I 2 = 80%). ARB prescription was not associated with significantly reduced AAA growth or a lower risk of AAA related events. The two RCTs had a low risk of bias, with one observational study having low, seven moderate, and one high risk of bias. All of the findings had a very low certainty of evidence based on the GRADE analysis. There was no association between ACEi or ARB prescription and AAA growth, but ACEi prescription was associated with a reduced risk of AAA rupture and AAA related events with very low certainty of evidence. [ABSTRACT FROM AUTHOR]

Drugs blocking the renin–angiotensin–aldosterone system may offer benefit on endothelial function, inflammation, and hemostasis in addition to the effects of reducing blood pressure. We have shown antithrombin effects by treatment with the angiotensin converting enzyme (ACE) inhibitor ramipril. As thrombin is a key inducer of platelet aggregation, we hypothesized that treatment with ramipril could modulate platelet reactivity and endothelial glycocalyx (eGCX) function. This study assessed platelet activity (CD40 ligand and P-selectin) and eGCX markers (E-selectin, hyaluronan, syndecan-1, and thrombomodulin) in 59 individuals with mild-to-moderate hypertension, randomized double-blind to ramipril 10 mg or doxazosin 8 mg od for 12 weeks. Ramipril and doxazosin similarly reduced blood pressure. Antihypertensive treatment reduced CD40 ligand (p

BackgroundData about the safety of ACEI/ARB use in early (

Background: The PARADIGM HF trial showed sacubitril/valsartan (SV) to be superior to enalapril in patients with reduced ejection fraction (HFrEF). Since its publication, several other randomized trials have compared SV to either an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) in HFrEF which showed conflicting results regarding mortality, hospitalizations, and quality of life scoring. Objective: To review randomized comparative trials of SV to either ACEI or ARB in patients with HFrEF. Methods: PubMed and Embase databases were used to identify randomized comparative trials. The text terms sacubitril, angiotensin neprilysin, and LCZ696 were used for both searches. Meta-analysis, retrospective, adhoc, and cohort studies were excluded. Results: 1476 and 3983 citations were reviewed on PubMed and Embase, respectively. Of these, 11 randomized comparative trials to either ACEI or ARB were included for analysis. The mortality/quality of life benefits of SV over enalapril in the PARADIGM HF were not corroborated in any of the other trials. The effect of hospitalizations for heart failure was inconsistent among trials. Exercise tolerance was not improved with SV versus enalapril. Conclusion: The results of the PARADIGM HF trial have largely not been confirmed in subsequent randomized comparative trials. [ABSTRACT FROM AUTHOR]

Objective: To observe the efficacy of different combinations of antihypertensive drugs in patients with nocturnal hypertension (NH), and provide reference for clinical work. Methods: A cross-sectional study was used to collect clinical data of NH patients diagnosed through ambulatory blood pressure monitoring during physical examinations at the First Affiliated Hospital of Hunan University of Medicine from January 2021 to December 2022. According to the different motheds of medication treatment for patients, NH patients were divided into single-drug group, dual-drug group and multi-drug group.Angiotensin converting enzyme inhibitor (ACEI)/ angiotensin Ⅱ receptor antagonist (ARB) or calcium antagonist was used in single-drug group, ACEI/ARB combined with calcium antagonist were used in double-drug group, and any three or four combinations of ACEI/ARB, calcium antagonists, β-blockers and diuretics were used in multi-drug group. The clinical data of the three groups of patients were analyzed and compared. Results: There were 829 patients with NH, including 294 cases (35.46%) in single-drug group, 400 cases (48.25%) in dual-drug group and 135 cases (16.29%) in multiple-drug group. After 6 months of drug treatment, the nocturnal systolic blood pressure (NSBP) and nocturnal diastolic blood pressure (NDBP) of patients in single-drug group, dual-drug group and multi-drug group showed significant differences compared to before treatment (P＜0.05)，among them, the NSBP and NDBP of patients in dual-drug group were significantly lower than those in single-drug group and multi-drug group, but there was no significant difference between the latter two groups (P＞0.05). The decreases in NSBP and NDBP in dual-drug group (21.75%, 20.06%) were greater than those in single-drug group (17.60%, 15.26%) and multi-drug group (18.23%, 16.51%, P＜0.05), respectively. Conclusion: All three motheds of medication treatment can effectively control nocturnal blood pressure, but ACEI/ARB combined with calcium antagonist are more effective in lowering nocturnal blood pressure.

ACE inhibitors, sartans, and sacubitril are among the most important drugs for the prevention of cardiovascular mortality and morbidity. At the same time, they are known to cause non-allergic bradykinin-mediated angioedema, a potentially fatal swelling of the mucosa and/or submucosa and deeper skin without signs of urticaria or pruritus, occurring mainly in the head and neck region. In contrast with hereditary angioedema, which is also mediated by bradykinin, angioedema triggered by these drugs is by far the most common subtype of non-allergic angioedema. The molecular mechanisms underlying this type of angioedema, which are discussed here, are not yet sufficiently understood. There are a number of approved drugs for the prevention and treatment of acute attacks of hereditary angioedema. These include inhibitors of bradykinin synthesis that act as kallkrein inhibitors, such as the parenterally applied plasma pool, and recombinant C1 esterase inhibitor, ecallantide, lanadelumab, and the orally available berotralstat, as well as the bradykinin receptor type 2 antagonist icatibant. In contrast, no diagnostic tools, guidelines, or treatments have yet been approved for the diagnosis and treatment of acute non-allergic drug-induced angioedema, although it is more common and can take life-threatening courses. Approved specific drugs and a structured diagnostic workflow are needed for this emergency diagnosis.

Drugs blocking the renin–angiotensin–aldosterone system may offer benefit on endothelial function, inflammation, and hemostasis in addition to the effects of reducing blood pressure. We have shown antithrombin effects by treatment with the angiotensin converting enzyme (ACE) inhibitor ramipril. As thrombin is a key inducer of platelet aggregation, we hypothesized that treatment with ramipril could modulate platelet reactivity and endothelial glycocalyx (eGCX) function. This study assessed platelet activity (CD40 ligand and P-selectin) and eGCX markers (E-selectin, hyaluronan, syndecan-1, and thrombomodulin) in 59 individuals with mild-to-moderate hypertension, randomized double-blind to ramipril 10 mg or doxazosin 8 mg od for 12 weeks. Ramipril and doxazosin similarly reduced blood pressure. Antihypertensive treatment reduced CD40 ligand (p <.001) with no interaction (p =.405) by treatment group (reductions by ramipril and doxazosin were 8.7 ± 30.8 ng/L, p =.044, and 13.4 ± 25.5 ng/L, p =.002, respectively). There were no changes in P-selectin by treatment within (p =.556) or between (p =.256) treatment groups. No changes were observed in E-selectin, hyaluronan, syndecan-1, or thrombomodulin by antihypertensive treatment (p =.091–.991), or between ramipril and doxazosin (p =.223–.999). Our results show a potential reduction of platelet activity by ACE inhibitor treatment. Also, the alpha 1-adrenoceptor antagonist doxazosin may reduce platelet activation. Neither drug influenced eGCX markers.What is the context Hypertension is a widely recognized risk factor for cardiovascular disease. Furthermore, hypertension is associated with a prothrombotic state Platelet activation may contribute to the increased risk of atherothrombotic complications with hypertension ACE inhibitor treatment may reduce thrombin generation beyond the effects on blood pressure reduction The effects of antihypertensive treatment on platelet activation show divergent results The integrity of the endothelial glycocalyx (eGCX) plays a vital role in vascular permeability, inflammation, and elasticity Injury or damage to the endothelial layer leads to a loss of the eGCX hemostatic protection, resulting in unrestricted platelet aggregation and accelerated fibrin clot formation In untreated hypertensive patients, eGCX dysfunction is linked to arterial stiffness, coronary artery disease, and myocardial dysfunction In hypertensive patients, endothelial function has been shown to improve with treatment of a high dose ACE inhibitor As thrombin is a key inducer of platelet aggregation, we hypothesized that treatment with ramipril could modulate platelet activity and eGCX function. What is new The effects of ACE inhibitor and/or alpha 1-adrenoceptor antagonist on platelet activation and eGCX in mild-to-moderate hypertensive subjects has previously not been investigated We here show that treatment with the ACE inhibitor ramipril in patient with mild-to-moderate hypertension reduced platelet activity, assessed by CD40 ligand The use of the alpha 1-adrenoceptor antagonist doxazosin also reduced platelet activation, assessed by CD40 ligand Antihypertensive treatment with an ACE inhibitor or an alpha 1-adrenoceptor antagonist in subjects with mild-to-moderate hypertension did not influence eGCX markers. What is the impact Our previous and present results suggest that treatment with ramipril reduces thrombin generation beyond the effect of blood pressure lowering; and in addition, treatment with ramipril may also reduce platelet activity The results suggest that treatment with ACE inhibitors may be a primary option for a patient with hypertension [ABSTRACT FROM AUTHOR]

ACE inhibitors, sartans, and sacubitril are among the most important drugs for the prevention of cardiovascular mortality and morbidity. At the same time, they are known to cause non-allergic bradykinin-mediated angioedema, a potentially fatal swelling of the mucosa and/or submucosa and deeper skin without signs of urticaria or pruritus, occurring mainly in the head and neck region. In contrast with hereditary angioedema, which is also mediated by bradykinin, angioedema triggered by these drugs is by far the most common subtype of non-allergic angioedema. The molecular mechanisms underlying this type of angioedema, which are discussed here, are not yet sufficiently understood. There are a number of approved drugs for the prevention and treatment of acute attacks of hereditary angioedema. These include inhibitors of bradykinin synthesis that act as kallkrein inhibitors, such as the parenterally applied plasma pool, and recombinant C1 esterase inhibitor, ecallantide, lanadelumab, and the orally available berotralstat, as well as the bradykinin receptor type 2 antagonist icatibant. In contrast, no diagnostic tools, guidelines, or treatments have yet been approved for the diagnosis and treatment of acute non-allergic drug-induced angioedema, although it is more common and can take life-threatening courses. Approved specific drugs and a structured diagnostic workflow are needed for this emergency diagnosis. [ABSTRACT FROM AUTHOR]

Background. Angioedema is the most common acute allergic presentation to emergency centres (EC), with hospitalisation rates increasing in high-income countries. Angioedema can complicate with life-threatening laryngeal obstruction. There are no local data; therefore, we aimed to characterise acute angioedema cases presenting to ECs and develop a simple management algorithm. Objective. To characterise the clinical presentation, management and outcomes of acute angioedema cases presenting to ECs. Based on these findings, we developed a management algorithm for acute angioedema to improve the care of acute angioedema in South Africa (SA). Methods. We conducted a retrospective folder review of all patients admitted to Groote Schuur Hospital (tertiary) and Mitchells Plain District Hospital (secondary) ECs from 1 June 2018 to 31 June 2020. Using ICD-10 coding, folders of adults ≥18 years with possible angioedema presenting to the ECs were screened. An allergist extracted demographics, medical history, management and outcome data for each angioedema event. Results. A total of 142 acute angioedema episodes were included, with a median (interquartile range) age of 42 (28 - 58) years, and 62% of patients were female. The majority (124/142, 87%) of acute angioedema EC presentations involved swelling above the shoulders, with airway involvement in 20 (14%) patients, with two patients requiring intubation. Nineteen (13%) patients required admission, with five (26%) admitted to high care/intensive care. Drug-induced angioedema was the most common cause, with 64/142 (45%) linked to a known offending drug, 42/64 (65.6%) being angiotensin-converting enzyme inhibitor (ACE-I). Critical information to guide angioedema management, including past personal/family allergy history, and duration of angioedema prior to EC visit, was not recorded in 64.7% and 37.8% of EC records, respectively. Unnecessary treatment with corticosteroids or antihistamines occurred in 19/53 (36%) and 16/53 (30%) cases with bradykinin-mediated angioedema ACE-I angioedema and hereditary angioedema). Overall, only 36/142 (25%) of angioedema patients were connected to allergy care. Conclusion. Angioedema is the most common allergy presentation to two ECs in Cape Town, SA. Bradykinin-mediated angioedema secondary to ACE-I therapy is the single most common offender, and was not appropriately managed in more than a third of cases. Based on these findings, we have developed a management algorithm that easily stratifies patients into bradykinin or mast cell-mediated angioedema with a step-by-step management approach that is applicable to the SA context. Ongoing awareness and education on allergy emergencies are required to ensure accurate diagnosis of less common causes of angioedema (particularly bradykinin-mediated angioedema) and linkage to allergy specialist care.

Chronic activation of the renin-angiotensin-aldosterone system (RAAS) promotes and perpetuates the syndromes of congestive heart failure, systemic hypertension, and chronic kidney disease. Excessive circulating and tissue angiotensin II (AngII) and aldosterone levels lead to a pro-fibrotic, -inflammatory, and -hypertrophic milieu that causes remodeling and dysfunction in cardiovascular and renal tissues. Understanding of the role of the RAAS in this abnormal pathologic remodeling has grown over the past few decades and numerous medical therapies aimed at suppressing the RAAS have been developed. Despite this, morbidity from these diseases remains high. Continued investigation into the complexities of the RAAS should help clinicians modulate (suppress or enhance) components of this system and improve quality of life and survival. This review focuses on updates in our understanding of the RAAS and the pathophysiology of AngII and aldosterone excess, reviewing what is known about its suppression in cardiovascular and renal diseases, especially in the cat and dog.

Risk for asthma in the overweight/obese may be mediated by adiponectin and peroxisome proliferator activated receptor pathways and may be reduced by the use of oral drugs impacting these pathways, such as angiotensin converting enzyme inhibitors (ACE-I), thiazolidinediones (TZD), and angiotensin receptor blockers (ARB). Our study objective was to determine whether ACE-I, TZD, and/or ARB use in overweight/obese adults with diabetes mellitus and/or hypertension is associated with a lower risk for incident asthma. Using an existing cohort of American veterans, we performed a longitudinal data analysis over 15 years. Exposure was defined by the prescription pickup of ACE-I, TZD, and/or ARB for at least 4 weeks. The outcome, time until new-onset of clinician-diagnosed asthma, was studied using survival analysis. The propensity scoring method controlled for treatment selection bias. 2.83 million eligible veterans, including 77,278 with incident asthma, were studied. As compared to those unexposed, the use of ACE-I alone, TZD alone, or their combinations were each associated with decreased risk for incident asthma (hazard ratios of 0.88, 0.74, and 0.20, respectively; p < 0.001 for all analyses in the fully adjusted statistical models). TZD lowered the risk among racial/ethnic minority subjects more than among White participants (p < 0.001). On the other hand, ARB use alone or in combination with TZD was associated with a higher risk for incident asthma. Use of ACE-I and/or TZD was associated with a lower risk for incident asthma in overweight/obese patients with diabetes mellitus and/or hypertension. [ABSTRACT FROM AUTHOR]

Abstract Background Hypotension that is resistant to phenylephrine is a complication that occurs in anesthetized patients treated with angiotensin converting enzyme (ACE) inhibitors. We tested the hypothesis that Ang 1–7 and the endothelial Mas receptor contribute to vasodilation produced by propofol in the presence of captopril. Methods The internal diameters of human adipose resistance arterioles were measured before and after administration of phenylephrine (10–9 to 10–5 M) in the presence and absence of propofol (10–6 M; added 10 min before the phenylephrine) or the Mas receptor antagonist A779 (10–5 M; added 30 min before phenylephrine) in separate experimental groups. Additional groups of arterioles were incubated for 16 to 20 h with captopril (10–2 M) or Ang 1–7 (10–9 M) before experimentation with phenylephrine, propofol, and A779. Results Propofol blunted phenylephrine-induced vasoconstriction in normal vessels. Captopril pretreatment alone did not affect vasoconstriction, but the addition of propofol markedly attenuated the vasomotor response to phenylephrine. A779 alone did not affect vasoconstriction in normal vessels, but it restored vasoreactivity in arterioles pretreated with captopril and exposed to propofol. Ang 1–7 reduced the vasoconstriction in response to phenylephrine. Addition of propofol to Ang 1–7-pretreated vessels further depressed phenylephrine-induced vasoconstriction to an equivalent degree as the combination of captopril and propofol, but A779 partially reversed this effect. Conclusions Mas receptor activation by Ang 1–7 contributes to phenylephrine-resistant vasodilation in resistance arterioles pretreated with captopril and exposed to propofol. These data suggest an alternative mechanism by which refractory hypotension may occur in anesthetized patients treated with ACE inhibitors.

Objective: To compare the safety and efficacy of valsartan/sacubitril (angiotensin receptor neprilysin inhibitor [ARNI]) against enalapril (angiotensin-converting enzyme inhibitor [ACEI]) in patients with acute heart failure at 6-month follow-up. Methods: In this prospective, single centre, and observational study conducted between September 2017 and February 2020 in India, patients with acute decompensated heart failure with reduced ejection fraction (

Abstract Background Activity of the circulating renin‐angiotensin‐aldosterone system (RAAS) has not been comprehensively characterized in cats with systemic hypertension (SH) or cardiomyopathy (CM), and the effects of furosemide or amlodipine treatment on the RAAS have not been fully evaluated in cats. Hypothesis/Objectives To document RAAS activity in cats with SH or CM compared to healthy cats and determine how RAAS profiles change with furosemide or amlodipine treatment. Animals Sixty‐six client‐owned cats: 15 with SH (7 amlodipine‐treated, 8 untreated), 17 with advanced CM (7 furosemide‐treated, 10 not furosemide‐treated), and 34 healthy cats. Methods Equilibrium concentrations of RAAS peptides and aldosterone were quantified in serum samples by liquid chromatography‐mass spectrometry. Variables were compared between groups using Kruskal‐Wallis analysis with post hoc Holms‐corrected Dunn's testing. Results Compared with healthy cats, cats with CM had higher concentrations of angiotensin I, aldosterone, and plasma renin activity (all P

Abstract Background This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia. Methods Placebo‐controlled, parallel group, double‐blind, randomized two‐by‐two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (

Introduction: The inducible form of nitric oxide (iNOS) is induced by cytokines and endotoxins. The cardiac-protective effects of nitric oxide (NO) secreted by endothelial NOS are dependent on arginine. Arginine production occurs mainly within the organism, with the kidneys playing a key role in its synthesis and the elimination of asymmetric dimethylarginine (ADM). In the present study the relationship between iNOS, ADMA and left ventricular hypertrophy in chronic kidney disease (CKD) patients and the effect of treatment with angiotensin converting enzyme inhibitor (ACEI) associated with vitamin C (Vit C) were investigated. Material and methods: A longitudinal observational study was conducted on 153 patients with CKD. We studied the correlation between the mean values of iNOS and ADMA in CKD patients and its relationship with left ventricular hypertrophy and the benefit of treating these patients with an associated ACEI and Vit C. Results: The mean age of the patients was 58.85 ±12.75 years. The mean values of iNOS and ADMA were 63.92 ± 0.59 μmol/l and 16.77 ±0.91 μmol/l, respectively. These values increased significantly with the degradation of the renal function (p < 0.05). A significant positive correlation was found between the left ventricular mass index (LVMI) and the two markers, ADMA (0.901 and p = 0001) and iNOS (0.718 and p = 0.0001). After 2 years of treatment with Vit C and ACEI, a significant decrease in LVMI was observed. Conclusions: NO secreted by the iNOS system and ADMAs initiates cardiac remodeling to lead to left ventricular hypertrophy and cardiac fibrosis. ACEIs increase the expression and activity of eNOS and decrease iNOS. Vit C prevents oxidative damage by scavenging ROS species and reagents nitrogen while. iNOS and ADMA accelerate cardiac aging. We conclude that ACEIs combined with Vit C may improve heart health and limite left ventricular hypertrophy in CKD patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to conduct a systematic review and meta-analysis to investigate the effect of the premorbid use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ACEI/ARB) on short-term mortality in patients with sepsis.Data Sources: Embase, the Cochrane Central Register of Controlled Trials, and MEDLINE were searched for studies based on the below eligibility criteria. The protocol was registered at the PROSPERO (CRD42022309129).Study Selection: Eligibility criteria were as follows: (1) randomized controlled trials, cohort studies, cross-sectional studies, (2) patients with sepsis aged ≥16 years, and (3) received premorbid ACEI/ARB, or not.Data Extraction: The patient and study characteristics and outcomes were extracted. All analyses were presented with the use of random-effects models. The primary outcome was short-term mortality defined as ≤30-day, in-hospital, or intensive care unit (ICU)- mortality. The secondary outcome was acute kidney injury (AKI).Data Synthesis: Fifteen studies (N = 96,159) met the eligibility criteria. Of these, eleven studies (N = 40,360) reported unadjusted short-term mortalities. The pooled odds ratio (OR) of short-term mortality with the premorbid use of ACEI/ARB was as follows: OR, 0.86; 95% confidence interval (CI), 0.67 to 1.11; P = 0.24, I2 = 88%. Five studies reported an adjusted OR of short-term mortality with the premorbid use of ACEI/ARB as follows: OR, 0.74; 95%CI, 0.59 to 0.93; P < 0.01, I2 = 93%. Seven studies reported the pooled adjusted OR of AKI with the premorbid use of ACEI/ARB as follows: OR: 1.57, 95%CI: 1.26-1.96, p < 0.01, I2 = 69%.Conclusion: In this meta-analysis, the premorbid ACEI/ARB was associated with significantly lower short-term mortality in patients with sepsis despite the significantly higher risk of AKI. [ABSTRACT FROM AUTHOR]

Introduction: Guidelines recommend angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB)/angiotensin receptor neprilysin inhibitors (ARNI); beta blockers; and mineralocorticoid receptor antagonists (MRA) in patients with symptomatic heart failure and reduced left ventricular ejection fraction before consideration of primary prevention implantable cardioverter defibrillator (ICD). This study aims to investigate dispensing rates of guideline-directed medical therapy (GDMT) before and after primary prevention ICD implantation in New Zealand.Methods: All patients receiving a primary prevention ICD between 2009 and 2018 were identified using nationally collected data on all public hospital admissions in New Zealand. This was anonymously linked to national pharmaceutical data to obtain medication dispensing. Medications were categorised as low dose (<50% of target dose), 50-99% of target dose or target dose based on international guidelines.Results: Of the 1,698 patients identified, ACEi/ARB/ARNI, beta blockers and MRA were dispensed in 80.2%, 83.6% and 45.4%, respectively, prior to ICD implant. However, ≥50% target doses of each medication class were dispensed in only 51.8%, 51.8% and 34.5%, respectively. Only 15.8% of patients were receiving ≥50% target doses of all three classes of medications. In the 1,666 patients who survived 1 year after ICD implant, the proportions of patients dispensed each class of medications remained largely unchanged.Conclusion: Dispensing of GDMT was suboptimal in patients before and after primary prevention ICD implantation in New Zealand, and only a minority received ≥50% target doses of all classes of medication. Interventions are needed to optimise use of these standard evidence-based medications to improve clinical outcomes and avoid unnecessary device implantation. [ABSTRACT FROM AUTHOR]

Objective: Patients with lupus nephritis (LN), including those below age 50, face significantly higher risk of atherosclerotic cardiovascular disease (ASCVD) vs. peers. This highlights the need for identifying specific ASCVD risk factors in LN. Renal arteriosclerosis in kidney biopsies (subclinical arteriosclerosis) may be able to predict future clinical ASCVD events. However, renal arteriosclerosis is under-reported in LN biopsies and is not taken into consideration when ASCVD risk is calculated. Therefore, we aimed to systematically grade renal arteriosclerosis in kidney biopsies at LN diagnosis and examined associations with 10- & 20-year ASCVD occurrence., Methods: Adults with biopsy proven LN were included. Clinical ASCVD, including fatal & non-fatal events, were adjudicated. Utilizing standard Banff grading criteria, all biopsies at LN diagnosis were re-read to grade renal arteriosclerosis. Covariables (e.g., socio-demographics, comorbidities, med exposure) were abstracted. Using Cox models, factors (including renal arteriosclerosis) associated with 10- & 20-year clinical ASCVD were examined., Results: Among 209 patients, 36 & 49 clinical ASCVD occurred within 10 & 20 years. Renal arteriosclerosis (>25%) was associated with 3x higher 10-year ASCVD. High area deprivation index (>80) & longer angiotensin converting enzyme inhibitor (ACEi) exposure were associated with 4x higher & 0.65x lower ASCVD occurrence. Adding renal arteriosclerosis >25% improved model performance for 10-year ASCVD risk estimation from 65% to 80%. Similar associations were seen with 20-year ASCVD., Conclusion: Renal arteriosclerosis >25%, area deprivation, ACEi exposure could inform ASCVD risk stratification in LN. Prospective studies should validate findings and inform clinical use., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Abstract Since the COVID‐19 pandemic, physicians concerned about the potential adverse effects of angiotensin converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs). To explore the relationship between ACEIs/ARBs and the risk of mortality and other clinical outcomes in COVID‐19 patients, the authors conducted a systemic review and meta‐analysis. An electronic search was performed from inception to November 12, 2020 in PubMed, Medline, EMBASE, ClinicalTrials, TRIP, the Cochrane Library, CNKI, Wanfang, and CBM database. Risk of bias was assessed using the Risk Of Bias In Non‐randomized Studies of Interventions tool. The primary outcome was in‐hospital all‐cause mortality. Secondary outcomes included all‐cause mortality measured at 30‐day or longer term, mechanical ventilation, length of hospital stay, readmission, and cardiac adverse events. A total of 28 studies with 73 465 patients was included. Twenty‐two studies with 19 871 patients reported the incidence of all‐cause mortality. Results showed no association between using ACEIs/ARBs and risk of mortality crude odds ratio （OR） of 1.02, 95% CI 0.71–1.46, p = .90, I2 = 88%, adjusted OR in 6260 patients of 0.96, 95% CI 0.77–1.18, p = .68, I2 = 0%. While six studies with 10 030 patients reported a lower risk of mortality in ACEIs/ARBs group hazard ratio (HR) of 0.53, 95% CI 0.34–0.84, p = .007, I2 = 68%. Similar association (for HR) was found in hypertension subgroup. There was no significant association for the secondary outcomes. Based on the available data, we concluded that ACEIs/ARBs is not associated with the risk of in‐hospital all‐cause mortality in COVID‐19 patients, but may be associated with a decreased risk of 30‐day all‐cause mortality. Patients with hypertension may benefit from using ACEIs/ARBs.

IntroductionRenin-angiotensin-system inhibitors (RASi) have shown survival benefits after acute myocardial infarction (MI), but the role of routine long-term use of RASi remains unclear. Thereby, we explored the therapeutic effects of RASi medication at 1-year follow-up from acute MI.MethodsUsing the nationwide Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) registry, we included and analyzed 10,822 subjects. Patients were stratified into those taking RASi at 1-year follow-up (n = 7,696) and those not taking RASi at 1-year follow-up (n = 3,126). Patients were followed up for 2-years from the 1-year follow-up; 2-year all-cause mortality and cardiac mortality were analyzed as primary and secondary outcomes, respectively.ResultsThe use of RASi at 1-year follow-up was not associated with decreased all-cause mortality (log-rank P = 0.195) or cardiac mortality (log-rank P = 0.337). In multivariate analyses, RASi medication at 1-year follow-up did not reduce all-cause mortality (P = 0.758) or cardiac mortality (P = 0.923), while RASi medication at discharge substantially reduced 1-year all-cause and cardiac mortality. Treatment with either an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker at 1-year follow-up did not show survival benefits from 1-year follow-up, respectively. The use of RASi at 1-year follow-up did not show a prognostic interaction between previous history of chronic kidney disease, post-MI acute heart failure, concomitant use of beta-blockers at 1-year follow-up, or 1-year LVEF.ConclusionAcute MI patients taking RASi at 1-year follow-up were not associated with improved 2-year all-cause mortality or cardiac mortality from the 1-year follow-up. This study provides valuable information regarding tailored medication strategy after acute MI.Clinical trial registration[www.ClinicalTrials.gov], identifier [KCT0000863].

Background: Hypotension that is resistant to phenylephrine is a complication that occurs in anesthetized patients treated with angiotensin converting enzyme (ACE) inhibitors. We tested the hypothesis that Ang 1–7 and the endothelial Mas receptor contribute to vasodilation produced by propofol in the presence of captopril. Methods: The internal diameters of human adipose resistance arterioles were measured before and after administration of phenylephrine (10–9 to 10–5 M) in the presence and absence of propofol (10–6 M; added 10 min before the phenylephrine) or the Mas receptor antagonist A779 (10–5 M; added 30 min before phenylephrine) in separate experimental groups. Additional groups of arterioles were incubated for 16 to 20 h with captopril (10–2 M) or Ang 1–7 (10–9 M) before experimentation with phenylephrine, propofol, and A779. Results: Propofol blunted phenylephrine-induced vasoconstriction in normal vessels. Captopril pretreatment alone did not affect vasoconstriction, but the addition of propofol markedly attenuated the vasomotor response to phenylephrine. A779 alone did not affect vasoconstriction in normal vessels, but it restored vasoreactivity in arterioles pretreated with captopril and exposed to propofol. Ang 1–7 reduced the vasoconstriction in response to phenylephrine. Addition of propofol to Ang 1–7-pretreated vessels further depressed phenylephrine-induced vasoconstriction to an equivalent degree as the combination of captopril and propofol, but A779 partially reversed this effect. Conclusions: Mas receptor activation by Ang 1–7 contributes to phenylephrine-resistant vasodilation in resistance arterioles pretreated with captopril and exposed to propofol. These data suggest an alternative mechanism by which refractory hypotension may occur in anesthetized patients treated with ACE inhibitors. [ABSTRACT FROM AUTHOR]

Background: Activity of the circulating renin‐angiotensin‐aldosterone system (RAAS) has not been comprehensively characterized in cats with systemic hypertension (SH) or cardiomyopathy (CM), and the effects of furosemide or amlodipine treatment on the RAAS have not been fully evaluated in cats. Hypothesis/Objectives: To document RAAS activity in cats with SH or CM compared to healthy cats and determine how RAAS profiles change with furosemide or amlodipine treatment. Animals: Sixty‐six client‐owned cats: 15 with SH (7 amlodipine‐treated, 8 untreated), 17 with advanced CM (7 furosemide‐treated, 10 not furosemide‐treated), and 34 healthy cats. Methods: Equilibrium concentrations of RAAS peptides and aldosterone were quantified in serum samples by liquid chromatography‐mass spectrometry. Variables were compared between groups using Kruskal‐Wallis analysis with post hoc Holms‐corrected Dunn's testing. Results: Compared with healthy cats, cats with CM had higher concentrations of angiotensin I, aldosterone, and plasma renin activity (all P <.01), and these differences remained significant (P <.03) after considering subgroups of untreated or furosemide‐treated cats. Compared with healthy cats, untreated cats with SH showed no differences in RAAS biomarkers, whereas amlodipine‐treated cats had higher concentrations of angiotensins I, II, III, IV, and 1‐7, aldosterone, and plasma renin activity (all P <.03). Multivariable analysis determined that furosemide and amlodipine treatments were independent predictors of increased RAAS biomarker concentrations. Conclusions and Clinical Importance: Cats with CM had increased RAAS activity, whereas cats with untreated SH did not. Furosemide and amlodipine both led to nonspecific activation of both classical and alternative RAAS pathways in cats. [ABSTRACT FROM AUTHOR]

Chao merupakan produk fermentasi tradisional dari daerah Sulawesi Selatan dengan bahan baku ikan tembang, garam dan nasi yang difermentasi dengan ragi tape dan ragi tempe. Penelitian ini menggunakan bakteri asam laktat (BAL) proteolitik Lactobacillus plantarum Ags1-3 dan P. acidilactici Ags7-3 sebagai co-starter untuk mempelajari perananan dan potensinya sebagai penghasil ACE inhibitor selama fermentasi chao ikan tembang. Penelitian ini terdiri dari tiga tahap yaitu fermentasi garam (20%) (A-B), fermentasi BAL (C-D), dan fermentasi campuran BAL dengan nasi terfementasi (E-F). Sebagai kontrol adalah chao yang difermentasi tanpa penambahan inokulum BAL. Selama fermentasi diamati kadar garam, aktivitas air, populasi mikroorganisme, produksi asam dan perubahan pH serta kadar protein terlarut dan aktivitas inhibitor Angiotensin Converting Enzyme (ACE). Hasil penelitian menunjukkan bahwa pada fermentasi garam (A-B) terjadi kenaikan kadar garam pada ikan tembang dari 10,75% menjadi 16,48% dan tidak terjadi pertumbuhan mikroorganisme pada tahap ini. Pada tahap fermentasi BAL (C-D), terjadi kenaikan jumlah bakteri dan total BAL lebih dari 2 siklus log, namun pada kontrol, jumlah bakteri dan total BAL lebih rendah. BAL proteolitik mendegradasi protein menjadi komponen yang lebih sederhana yang ditandai dengan kenaikan yang nyata pada kadar protein terlarutnya dan tidak terjadi penurunan pH. Isolat BAL proteolitik berpotensi menghasilkan inhibitor ACE yang ditandai dengan aktivitas ACE-I mencapai 84-85%, sedang pada kontrol, aktivitas penghambatan ACE pada ikan yang difermentasi hanya 58%. Pada fermentasi campuran (E-F) terjadi peningkatan produksi asam dan penurunan pH yang nyata karena tersedianya sumber karbon yang berasal dari nasi terfermentasi. Fermentasi chao tanpa penambahan inokulum juga terjadi penurunan pH, namun nilai pHnya lebih tinggi. Fermentasi chao dengan penambahan inokulum BAL proteolitik berpotensi menghasilkan aktivitas penghambatan ACE dan dapat memperpendek waktu fermentasi.

Aims: The aim of the sudy was to evaluate potential role of oral captopril, an angiotensin-converting enzyme (ACE) inhibitor, and in treatment of infantile hemagioma (IH) and report our preliminary results. Methods: This prospective study included 18 children with IH admitted in the department of pediatric surgery with no history of prior treatment of any type. Baseline blood pressure (BP), electrocardiogram, two-dimensional echocardiography, serum electrolytes, and renal function test (RFT) were noted. Oral captopril was started as first-line drug at a dose of 0.1 mg/kg orally 12 h with gradually increase of dosage up to 2.0 mg/kg 12 h over the period of 10 days with monitoring of BP, serum electrolytes, RFT, and occurrence of any side effect. If no side effects were noted and patients were stable, they were discharged and followed up until 6 months after stopping treatment. During follow-up, response to treatment was documented clinically and photographically. Development of any side effect was also noted. Results: Excellent response to captopril was noticed in nine patients over 16–18 months. Four patients showed good response. Oral propranolol had to be administered alternatively in one patient showing fair response during the initial 4 months but no response afterward and in four patients showing no response at all. One patient developed an allergic reaction to propranolol and was started oral corticosteroid. These five patients had near complete resolution of lesion for the next 8–10 months. Conclusions: ACE inhibitors might have a role, though slow, in the involution of IHs. Therefore, these may have the potential to emerge as an alternative treatment for IH in future after confirmation with randomized studies with propranolol.

Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) induces numerous symptoms affecting patient quality of life, leading to decreased doses or even to cessation of anticancer therapy. Previous studies have reported that a widely used drug, ramipril, improves neuroprotection in several rodent models of peripheral neuropathy. The protective role of the angiotensin II type 2 receptor (AT2) in the central and peripheral nervous systems is well-established. Here, we evaluate the effects of ramipril in the prevention of PIPN and the involvement of AT2 in this effect. Paclitaxel was administered in wild type or AT2-deficient mice on alternate days for 8 days, at a cumulative dose of 8 mg/kg (2 mg/kg per injection). Ramipril, PD123319 (an AT2 antagonist), or a combination of both were administered one day before PTX administration, and daily for the next twenty days. PTX-administered mice developed mechanical allodynia and showed a loss of sensory nerve fibers. Ramipril prevented the functional and morphological alterations in PTX mice. The preventive effect of ramipril against tactile allodynia was completely absent in AT2-deficient mice and was counteracted by PD123319 administration in wild type mice. Our work highlights the potential of ramipril as a novel preventive treatment for PIPN, and points to the involvement of AT2 in the neuroprotective role of ramipril in PIPN. [ABSTRACT FROM AUTHOR]

Background: Preclinical evidence suggests a link between the renin‐angiotensin system and oncogenesis. We aimed to explore the impact of angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) in head and neck cancer (HNC). Methods: Over 5000 patients were identified from the Surveillance, Epidemiology, and End Results‐Medicare linked dataset and categorized according to ACEi and ARB and diagnoses of chronic kidney disease (CKD) or hypertension (HTN). Overall survival (OS) and cancer‐specific survival (CSS) were compared using Cox multivariable regression (MVA), expressed as hazard ratios (HR) with 95% confidence intervals (95%CI). Results: No significant MVA associations for OS or CSS were found for ACEi. Compared to patients with CKD/HTN taking ARB, those with CKD/HTN not taking ARB experienced worse OS (HR 1.28, 95%CI 1.09–1.51, p = 0.003) and CSS (HR 1.23, 95%CI 1.00–1.50, p = 0.050). Conclusions: ARB usage is associated with improved OS and CSS among HNC patients with CKD or HTN. [ABSTRACT FROM AUTHOR]

Since the COVID‐19 pandemic, physicians concerned about the potential adverse effects of angiotensin converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs). To explore the relationship between ACEIs/ARBs and the risk of mortality and other clinical outcomes in COVID‐19 patients, the authors conducted a systemic review and meta‐analysis. An electronic search was performed from inception to November 12, 2020 in PubMed, Medline, EMBASE, ClinicalTrials, TRIP, the Cochrane Library, CNKI, Wanfang, and CBM database. Risk of bias was assessed using the Risk Of Bias In Non‐randomized Studies of Interventions tool. The primary outcome was in‐hospital all‐cause mortality. Secondary outcomes included all‐cause mortality measured at 30‐day or longer term, mechanical ventilation, length of hospital stay, readmission, and cardiac adverse events. A total of 28 studies with 73 465 patients was included. Twenty‐two studies with 19 871 patients reported the incidence of all‐cause mortality. Results showed no association between using ACEIs/ARBs and risk of mortality crude odds ratio （OR） of 1.02, 95% CI 0.71–1.46, p =.90, I2 = 88%, adjusted OR in 6260 patients of 0.96, 95% CI 0.77–1.18, p =.68, I2 = 0%. While six studies with 10 030 patients reported a lower risk of mortality in ACEIs/ARBs group hazard ratio (HR) of 0.53, 95% CI 0.34–0.84, p =.007, I2 = 68%. Similar association (for HR) was found in hypertension subgroup. There was no significant association for the secondary outcomes. Based on the available data, we concluded that ACEIs/ARBs is not associated with the risk of in‐hospital all‐cause mortality in COVID‐19 patients, but may be associated with a decreased risk of 30‐day all‐cause mortality. Patients with hypertension may benefit from using ACEIs/ARBs. [ABSTRACT FROM AUTHOR]

Cardiorenal syndrome in patients with heart failure is a regular link in the chain of cardiorenal continuum. Physicians of various specialties may encounter patients with cardiorenal syndrome: general practitioners, cardiologists, nephrologists, resuscitators, anesthetists, cardiac surgeons, etc. The currently definition, classification, pathogenesis, diagnosis and epidemiology of cardiorenal syndrome in patients with heart failure were presented in first part of our review. In the second part, prognosis, approaches to the prevention and treatment of cardiorenal syndrome in patients with heart failure are discussed. They include the treatment of cardiovascular pathology and heart failure in accordance with current guidelines for the prevention of episodes of acute and decompensated chronic heart failure; diet; smoking cessation, alcohol, nephrotoxic substances; body weight, blood pressure and glycemia control; angiotensin converting enzyme inhibitors, angiotensin receptor antagonists or angiotensin receptors and neprilisin inhibitors (ARNI), statins; reducing of the abdominal pressure and others. It is necessary to develop and introduce new approaches to nephroprotection in patients with cardiorenal syndrome, which is possible with the joint work of a multidisciplinary team.

Purpose The use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) to treat hypertension (HTN) during pregnancy presents well-established risks to a developing fetus. A cross-sectional study was conducted to evaluate the current state of antihypertensive prescribing and contraceptive use in females of childbearing age within a large safety-net health system. Methods The retrospective cross-sectional study focused on females aged 18-49 years with a documented diagnosis of HTN. The proportion of patients prescribed an ACE inhibitor or ARB and using a documented form of contraception was calculated. Documented forms of contraception included oral contraceptives, intrauterine devices, injections, implants, and surgical intervention. Results A total of 4,187 patients were identified from the HTN registry; after application of exclusion criteria 3,045 patients were included in the study population. The mean age was 39 years (range, 18-49 years). The most frequently prescribed classes of antihypertensive medications were ACE inhibitors and ARBs (one or the other was used by 1,146 patients [37.6%]), followed by thiazide diuretics (n = 710, 23.3%) and calcium channel blockers (n = 599, 19.7%). Of the 1,146 patients prescribed an ACE inhibitor or ARB, 553 (48%) were using a documented form of contraception. Conclusion Rates of ACE inhibitor or ARB prescribing to females of childbearing age were high despite the teratogenic risks, and fewer than half of patients had documented protection from pregnancy. Provider and patient education and potential creation of best practice alerts in the electronic medical record regarding the risks of using ACE inhibitors and ARBs in females of childbearing age are warranted. [ABSTRACT FROM AUTHOR]

Aims: The aim of the sudy was to evaluate potential role of oral captopril, an angiotensin-converting enzyme (ACE) inhibitor, and in treatment of infantile hemagioma (IH) and report our preliminary results. Methods: This prospective study included 18 children with IH admitted in the department of pediatric surgery with no history of prior treatment of any type. Baseline blood pressure (BP), electrocardiogram, two-dimensional echocardiography, serum electrolytes, and renal function test (RFT) were noted. Oral captopril was started as first-line drug at a dose of 0.1 mg/kg orally 12 h with gradually increase of dosage up to 2.0 mg/kg 12 h over the period of 10 days with monitoring of BP, serum electrolytes, RFT, and occurrence of any side effect. If no side effects were noted and patients were stable, they were discharged and followed up until 6 months after stopping treatment. During follow-up, response to treatment was documented clinically and photographically. Development of any side effect was also noted. Results: Excellent response to captopril was noticed in nine patients over 16–18 months. Four patients showed good response. Oral propranolol had to be administered alternatively in one patient showing fair response during the initial 4 months but no response afterward and in four patients showing no response at all. One patient developed an allergic reaction to propranolol and was started oral corticosteroid. These five patients had near complete resolution of lesion for the next 8–10 months. Conclusions: ACE inhibitors might have a role, though slow, in the involution of IHs. Therefore, these may have the potential to emerge as an alternative treatment for IH in future after confirmation with randomized studies with propranolol. [ABSTRACT FROM AUTHOR]

Introduction: Angiotensin converting enzyme inhibitors (ACEIs) are widely prescribed medications. A recent British study reported a 14% increased risk of lung cancer with ACEI versus angiotensin receptor blocker (ARB) prescriptions, and risk increased with longer use. We sought to validate this observation. Methods: We searched the Intermountain Enterprise Data Warehouse from 1996 to 2018 for patients newly treated with an ACEI or an ARB and with ≥1 year's follow-up or to incident lung cancer or death. Unadjusted and adjusted hazard ratios (HRs) for lung cancer and for lung cancer or all-cause mortality were calculated for ACEIs compared to ARBs. Results: A total of 187,060 patients met entry criteria (age 60.2 ± 15.1 y; 51% women). During a mean of 7.1 years follow-up (max: 20.0 years), 3,039 lung cancers and 43,505 deaths occurred. Absolute lung cancer rates were 2.16 and 2.31 per 1000 patient-years in the ARB and ACEI groups, respectively. The HR of lung cancer was modestly increased with ACEIs (unadjusted HR = 1.11, CI: 1.02, 1.22, P =.014; adjusted HR = 1.18, CI: 1.06, 1.31, P =.002; number needed to harm [NNH] 6,667). Rates of the composite of lung cancer or death over time also favored ARBs. Lung cancer event curves separated gradually over longitudinal follow-up beginning at 10-12 years. Conclusions: We noted a small long-term increase in lung cancer risk with ACEIs compared with ARBs. Separation of survival curves was delayed until 10-12 years after treatment initiation. Although the observed increases in lung cancer risk are small, implications are potentially important because of the broad use of ACEIs. Thus, additional work to validate these findings is needed. [ABSTRACT FROM AUTHOR]

Objective To Meta-analysis of Huangkui capsulesin treatment of diabetic kidney disease (DKD). Methods Retrieved from China Biomedical Literature Database (CBM), China Journal Full-Text Database (CNKI). VIP Periodical Database (VIP), Wanfang Database. PubMed. Empase. Cochrane Library. Web of Science randomized controlled trials about Abelmoschus Manihot with ACEI/ARB(test group) versus ACEI/ARB alonel control group) in the treatment of DKD were collected. After se lection data extraction and quality evaluation by two researchers independently, meta-analysis was performed by using Reyman 5.3 software. Results A total of 11 studies were included.involving 997 patients. Results of Meta analysis showed that compared with control group. test group could decrease the 24h urine albumin excretion rate (UAER) [MD-23, 25, 95% CIX-27. 04. -19. 46).P<0.05] and urea nitrogen (BUN) [MD=-0.22.95%CI(-0.13.-0.01).P<0.05]. However, in terms of reducing serum creatinine (Ser) levels. the treatment effect of the experimental group was not significantly different from that of the control group[MD=-0.81.95%CI(-3. 48.1. 86).P>0.05]. Conclusion Huangkui capsule combined with ACEI ARB drugs can reduce UAER in patients with DKD compared with ACEI/ARB drugs alone, but the renal function improved need to further research. [ABSTRACT FROM AUTHOR]

The coprescription of an angiotensin-converting enzyme inhibitor (ACEi) with clopidogrel reportedly increases bleeding risk. However, studies have not described such an increase in cases of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). We analyzed electronic medical records of patients with discharge records of having undergone DAPT after PCI from a national health insurance claims database for January 1, 2006 to December 31, 2014. The date of PCI was the index date, and the primary outcome was major bleeding. The unit of analysis was one person-quarter. We compared patients who were prescribed with those not prescribed an ACEi in the cohort. A Poisson model with inverse probability of treatment weighting was fitted using generalized estimating equations to measure the risk of outcomes. In total, 193,258 patients underwent DAPT after PCI; 46% had a coprescription of an ACEi. After screening, 170,775 patients (479,263 person-quarters) remained for analysis. The mean patient age was 65 ± 13 years, and 73.43% were men. In total, 79,739 prescriptions of an ACEi were written: 57%, 14.21%, 8.88%, 7.17%, and 4.68% were for captopril, ramipril, enalapril, perindopril, and imidapril, respectively. A concomitant prescription of an ACEi with clopidogrel was not associated with increased bleeding risk (adjusted rate ratio: 1.08, 99% confidence interval: 0.99–1.17). The coadministration of an ACEi with clopidogrel after PCI is common. In this real-world cohort study, such coadministration was not associated with an increased risk of major bleeding in patients undergoing DAPT after PCI. [Display omitted] • Co-prescription of angiotensin-converting enzyme inhibitor (ACEi) with clopidogrel has been reported with bleeding. • Such bleeding has not been described in the setting of dual antiplatelet therapy (DAPT) post percutaneous coronary intervention (PCI). • In this study, 170,775 patients, totalling 479,263 person-quarters, were analyzed. • Co-administration of ACEi with clopidogrel is a common practice after PCI. • There was no increased risk of major bleeding in the setting of DAPT post PCI. [ABSTRACT FROM AUTHOR]

Inhibition of the renin-angiotensin-aldosterone system (RAAS) is a key strategy in treating hypertension in cardiovascular and renal diseases. However, RAAS inhibitors (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone receptor antagonists, and direct renin inhibitors) increase the risk of hyperkalemia (serum potassium >5.5 mmol/L). This poses a therapeutic challenge because these patient groups comprise in whom the drugs are therapeutically indicated. Important considerations when initiating ACEI or ARB therapy include obtaining an estimate of glomerular filtration rate and a baseline serum potassium concentration, as well as assessing whether the patient has excessive potassium intake from diet, supplements, or drugs that can also increase serum potassium. Serum potassium monitoring shortly after initiation of therapy can assist in preventing hyperkalemia. If hyperkalemia does develop, prompt recognition of cardiac dysrhythmias and effective treatment to antagonize the cardiac effects of potassium, redistribute potassium into cells, and remove excess potassium from the body is important. Understanding the mechanism of action and monitoring of ACEI and ARB coupled with judicious drug use and clinical vigilance can minimize the risk to the patient of developing hyperkalemia.

Expert Council opinion describes emergency care in a sudden individually significant blood pressure (BP) increase without clinically overt target organ damage. In the new guidelines of the Russian Society of Cardiology, the term “hypertensive urgency” was abolished, and the management of a sudden BP increase was changed. At the same time, a sudden individually significant BP increase may be accompanied by symptoms that reduce patients’ quality of life and ability to work. According to experts, individually significant BP increase accompanied by symptoms requires outpatient treatment using oral rapid-onset drugs with an optimal duration of action, in particular captopril. It has a much evidence-based data on the BP increase use and sublingual administration, and also has a favorable safety profile, which allows prescribing to patients with comorbid diseases. The rationale for the use of angiotensin-converting enzyme inhibitor Capoten (captopril) as a drug for self-management of a sudden individually significant BP increase accompanied by symptoms in hypertension patients is describes.

Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) induces numerous symptoms affecting patient quality of life, leading to decreased doses or even to cessation of anticancer therapy. Previous studies have reported that a widely used drug, ramipril, improves neuroprotection in several rodent models of peripheral neuropathy. The protective role of the angiotensin II type 2 receptor (AT2) in the central and peripheral nervous systems is well-established. Here, we evaluate the effects of ramipril in the prevention of PIPN and the involvement of AT2 in this effect. Paclitaxel was administered in wild type or AT2-deficient mice on alternate days for 8 days, at a cumulative dose of 8 mg/kg (2 mg/kg per injection). Ramipril, PD123319 (an AT2 antagonist), or a combination of both were administered one day before PTX administration, and daily for the next twenty days. PTX-administered mice developed mechanical allodynia and showed a loss of sensory nerve fibers. Ramipril prevented the functional and morphological alterations in PTX mice. The preventive effect of ramipril against tactile allodynia was completely absent in AT2-deficient mice and was counteracted by PD123319 administration in wild type mice. Our work highlights the potential of ramipril as a novel preventive treatment for PIPN, and points to the involvement of AT2 in the neuroprotective role of ramipril in PIPN.

Abstract Background The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. T2DM is associated with serious macro- and microvascular complications. In particular, diabetic kidney disease (DKD), which begins with excessive urinary albumin excretion, has a significant impact on affected individuals and is costly to healthcare services. Inhibition of the renin–angiotensin–aldosterone system (RAAS) with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) significantly reduces albuminuria in diabetes, but this effect is not observed in all those treated. Active vitamin D analogues have been observed to be reno-protective through inhibition of RAAS in animal and human studies. Therefore, it can be hypothesised that an active vitamin D analogue will have an additional benefit to ACEI/ARB treatment for albuminuria reduction in DKD. Methods The planned study is an ongoing non-blinded randomised controlled parallel-group trial examining the impact, in individuals with T2DM, of the addition of bioactive vitamin D (calcitriol) to RAAS inhibition treatment using ACI or ARB on urinary albumin excretion over a period of 26 weeks. The primary outcome measure is the urinary albumin creatinine ratio. It is planned for the study to recruit 320 participants. Other outcome measures of interest include 24-h urine albumin (24 h UA) excretion, estimated glomerular filtration rate (eGFR), blood pressure and quality of life. Safety will be assessed throughout. Discussion If the addition of calcitriol to RAAS inhibition with ACEI or ARB safely results in a significant reduction in albuminuria, the study adds to the body of evidence supporting a role for vitamin D in reno-protection, will inform clinical practice and could result in significant reduction of healthcare costs associated with DKD. Trial registration ISRCTN, ISRCTN86739609. Registered on 7 June 2017. ClinicalTrials.gov, NCT03216564. Registered on 13 July 2017.

Considerable concern has emerged for the potential harm in the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor inhibitors (ARBs) in COVID-19 patients, given that ACEIs and ARBs may increase the expression of ACE2 receptors that represent the way for coronavirus 2 to entry into the cell and cause severe acute respiratory syndrome. Assess the effect of ACEI/ARBs on outcome in COVID-19 patients. Hospital-based prospective study. A total of 431 patients consecutively presenting at the Emergency Department and found to be affected by COVID-19 were assessed. Relevant clinical and laboratory variables were recorded, focusing on the type of current anti hypertensive treatment. Outcome variables were NO, MILD, SEVERE respiratory distress (RD) operationally defined and DEATH. Hypertension was the single most frequent comorbidity (221/431 = 51%). Distribution of antihypertensive treatment was: ACEIs 77/221 (35%), ARBs 63/221 (28%), OTHER than ACEIs or ARBs 64/221 (29%). In 17/221 (8%) antihypertensive medication was unknown. The proportion of patients taking ACEIs, ARBs or OTHERs who developed MILD or SEVERE RD was 43/77 (56%), 33/53 (52%), 39/64 (61%) and 19/77 (25%), 16/63 (25%) and 16/64 (25%), respectively, with no statistical difference between groups. Despite producing a RR for SEVERE RD of 2.59 (95% CI 1.93–3.49), hypertension was no longer significant in a logistic regression analysis that identified age, CRP and creatinine as the sole independent predictors of SEVERE RD and DEATH. ACEIs and ARBs do not promote a more severe outcome of COVID-19. There is no reason why they should be withheld in affected patients. [ABSTRACT FROM AUTHOR]

and Aims; To investigate the association between use of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB) and outcomes of hypertensive COVID-19 patients, a systematic review and meta-analysis were performed. We systematically searched PubMed, EuropePMC, ProQuest, and Cochrane Central Databases using the terms "(COVID-19 OR SARS-CoV-2) AND (angiotensin converting enzyme OR angiotensin receptor blocker)". The primary and second outcomes were mortality (non-survivor) and severe COVID-19, respectively. Totally, 7410 patients were included from 15 studies. Pooled analysis showed that the use of ACEI/ARB was not associated with mortality (OR 0.73 [0.38, 1.40], p = 0.34; I2: 81%) and severity (OR 1.03 [0.73, 1.45], p = 0.87; I2: 65%). Pooled adjusted OR showed no risk/benefit associated with ACEI/ARB use in terms of mortality (OR 0.83 [0.54, 1.27], p = 0.38; I2: 0%). Subgroup analysis showed that the use of ARB was associated with reduced mortality (OR 0.51 [0.29, 0.90], p = 0.02; I2: 22%) but not ACEI subgroup (OR 0.68 [0.39, 1.17], p = 0.16; I2: 0%). Meta-regression showed that the association between ACEI/ARB use and mortality in patients with COVID-19 do not varies by gender (p = 0.104). GRADE showed a very low certainty of evidence for effect of ACEI/ARB on mortality and severity. The certainty of evidence was very low for both ACEI and ARB subgroups. Administration of a renin angiotensin system (RAS) inhibitor, was not associated with increased mortality or severity of COVID-19 in patients with hypertension. Specifically, ARB and not ACEI use, was associated with lower mortality. • The use of RAS inhibitor did not increase/decrease mortality in patients with COVID-19. • Subgroup analysis for ARB showed reduced mortality rate in patients with COVID-19. • The certainty of evidence was very low and randomized controlled trials are still required. [ABSTRACT FROM AUTHOR]

Angioedema (AE) is a transient capillary leak syndrome, caused by either histamine or bradykinin, that presents as an acute nonpitting swelling of the skin, subcutaneous tissues, and mucous membranes of the face, lips, tongue, upper airways, and gastrointestinal tract, with or without a rash. A lack of response to antihistamines, steroids, and epinephrine suggests a bradykinin-mediated AE. Bradykinin-AE may be inherited, acquired, or drug related. Mechanism of increased bradykinin can include decreased C1-esterase inhibitor (C1-INH) levels or activity, increased bradykinin production, or decreased bradykinin breakdown, the latter occurring during angiotensin converting enzyme inhibitor (ACEi). A 65-year-old woman had coronary artery bypass grafting, which was complicated by prolonged bradykinin-AE owing to ACEi, requiring prolonged endotracheal tube intubation. Treatment with a C1-esterase inhibitor (Berinert) on postoperative day 7 resulted in a dramatic improvement in airway edema and tongue swelling within 7 hours, and the patient was subsequently extubated. The case is unusual because of the prolonged course of AE and the benefit of late administration of C1-INH concentrate. [ABSTRACT FROM AUTHOR]