Safety and efficacy of ARNI (valsartan/sacubitril) vs ACEI (enalapril) in acute heart failure – A prospective observational study

ObjectiveTo 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.MethodsIn 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 (<40%) were included. Patients were divided in two groups: valsartan/sacubitril (ARNI) group and enalapril (ACEI). Patients were followed up for at least 6 months after administration of first dose and were evaluated for safety, efficacy, and tolerability of target drug. Student's independent t-test was employed for comparing continuous variables. Chi-square test or Fisher's exact test, whichever appropriate, was applied for comparing categorical variables.ResultsA total of 200 patients were included in the present study, 100 each in ARNI and ACEI group. The mean age of the population was 61.2 ± 8.4 years and 62.6 ± 8.6 years in ARNI group and ACEI group, respectively. The mean maximum tolerated dose by population in ARNI group was 203.6 mg and 8.9 mg in ACEI group. Readmission for heart failure were seen significantly higher in ACEI group than ARNI group (p value = 0.001). Parameters like ejection fraction, left ventricular end diastolic and systolic dimensions, 6 min walk test and Kansas City Cardiomyopathy Questionnaires (KCCQ) showed p values < 0.05 between the groups.ConclusionThe ARNI study group showed better safety and efficacy outcomes at the end of 6 months follow-up compared to ACEI group.     

Angiotensin-converting enzyme (ACE) gene polymorphisms and familial occurrence of sarcoidosis

OBJECTIVES: The aim of this study was to test for genetic linkage and association between polymorphisms of the angiotensin-converting enzyme (ACE) gene and familial occurrence of sarcoidosis. DESIGN, SETTING AND SUBJECTS: German families with more than one member suffering from sarcoidosis were contacted and a DNA bank was established. Sixty-two families (140 patients, 77 females and 63 males, and 104 unaffected relatives) were genotyped for the ACE gene insertion/deletion (I/D) polymorphism and for two flanking variable sites (ACE A-5466C and ACE 4656(CT)2/3). As controls, 100 DNAs from unrelated resident Caucasians (50 females, 50 males) were analysed. ACE allele and genotype frequencies were determined, and parametric linkage and affected sib pair analyses and transmission disequilibrium tests were performed. RESULTS: There was a striking over-representation of the ACE I/D genotype DD in patients with sarcoidosis and their families as compared with controls of the study and well founded genotype frequencies from the literature. The same was evident for the accompanying genotypes CC and 2,2 of the flanking polymorphisms. Linkage between the segregation of ACE alleles and the disorder within families was clearly excluded for simple models of inheritance. However, there was a suggestive but not significant (P = 0.06) excess of allele sharing amongst affected siblings. There was no transmission disequilibrium for any ACE allele or haplotype. CONCLUSIONS: ACE is involved in the pathogenesis of sarcoidosis, but the ACE polymorphisms are not an inherited main cause of the disease. They are more likely to modify the development of the disorder, and the ACE I/D genotype DD might be a promoter to clinical manifestation.     

Elimination of early rehospitalization in a randomized, controlled trial of multidisciplinary care in a high-risk, elderly heart failure population: the potential contributions of specialist care, clinical stability and optimal angiotensin-converting enzyme inhibitor dose at discharge

BACKGROUND: Despite a growing body of data demonstrating the benefits of multidisciplinary care in heart failure, persistently high rates of readmission, especially within the first month of discharge, continue to be documented. AIMS: As part of an ongoing randomized study on the value of multidisciplinary care in a high risk (NYHA Class IV), elderly (mean age 69 years) heart failure population, we examined the effects of this intervention on previously high (20%) 1-month readmission rates. METHODS: Unlike previous studies of this approach, both multidisciplinary (MC) and routine care (RC) populations were cared for by the cardiology service, complied with adherence to clinical stability criteria prior to discharge (100% of patients) and received at least target dose angiotensin-converting enzyme (ACE) inhibition with perindopril prior to discharge (94% of indicated patients). We analysed death and unplanned readmission for heart failure at 1 month. RESULTS: This early report from the first 70 patients (67% male, 71% systolic dysfunction with a mean ejection fraction of 31.0+/-6.7%) enrolled in this study demonstrates elimination of 1-month hospital readmission in both RC and MC groups. This unexpected result represents a dramatic improvement both for this patient cohort (20% 30-day readmission rate prior to enrollment reduced to 0% following the index admission in both care groups) and in comparison with available data. CONCLUSIONS: Critical contributors to this improvement appear to be specialist cardiology care, adherence to clinical stability criteria prior to discharge and routine use of target or high-dose ACE inhibitor therapy prior to discharge. Widespread application of this approach may have a dramatic improvement in morbidity of CHF while limiting the escalating costs of this condition.     

Angiotensin receptor blockers: evidence for preserving target organs

Hypertension is a major problem throughout the developed world. Although current antihypertensive treatment regimens reduce morbidity and mortality, patients are often noncompliant, and medications may not completely normalize blood pressure. As a result, current therapy frequently does not prevent or reverse the cardiovascular remodeling that often occurs when blood pressure is chronically elevated. Blockade of the renin-angiotensin system (RAS) is effective in controlling hypertension and treating congestive heart failure. Both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) inhibit the activity of the RAS, but these two classes of antihypertensive medications have different mechanisms of action and different pharmacologic profiles. Angiotensin-converting enzyme inhibitors block a single pathway in the production of angiotensin II (Ang II). In addition, angiotensin I is not the only substrate for ACE. The ACE inhibitors also block the degradation of bradykinin that may have potential benefits in cardiovascular disease. Bradykinin is, however, the presumed cause of cough associated with ACE inhibitor therapy. Data from clinical trials on ACE inhibitors serve to support the involvement of the RAS in the development of cardiovascular disease. Angiotensin receptor blockers act distally in the RAS to block the Ang II type 1 (AT1) receptor selectively. Thus, ARBs are more specific agents and avoid many side effects. Experimental and clinical trials have documented the efficacy of ARBs in preserving target-organ function and reversing cardiovascular remodeling. In some instances, maximal benefit may be obtained with Ang II blockade using both ARBs and ACE inhibitors. This review describes clinical trials that document the efficacy of ARBs in protecting the myocardium, blood vessels, and renal vasculature.     

Clinical update: the role of angiotensin II receptor blockers in patients with left ventricular dysfunction (Part II of II)

Almost 5 million individuals in the United States have chronic heart failure (HF), which is increasing in prevalence. Angiotensin-converting enzyme (ACE) inhibitors are standard therapies for HF, although more than 10% of patients with HF are unable to tolerate these agents. Furthermore, ACE inhibitors may not provide complete blockade of the renin-angiotensin system (RAS) in the long term. Because angiotensin II receptor blockers (ARBs) may block the RAS more completely than ACE inhibitors and are better tolerated, several large-scale ARB trials have been performed exploring their potential role in treating patients with symptomatic HF and left ventricular systolic dysfunction. The Losartan Heart Failure Survival Study (ELITE II) demonstrated no significant differences in morbidity and mortality between the ARB losartan and the ACE inhibitor captopril among elderly patients with HF. The Valsartan Heart Failure Trial (Val-HeFT) demonstrated reductions in hospitalizations for HF with the ARB valsartan when added to standard HF therapy, with no effect on mortality. Both trials suggested a potential negative interaction between ARB and beta-blocker therapy. The Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) program demonstrated significant reductions in morbidity and mortality with the ARB candesartan in patients with HF due to systolic dysfunction, with or without ACE inhibitors and with or without beta blockers. Thus, the addition of ARBs to the treatment regimen of patients with symptomatic HF should be strongly considered.     

Angiotensin converting enzyme inhibitor and angiotensin receptor blockade use in relation to outcomes in anticoagulated patients with atrial fibrillation

BACKGROUND: The renin-angiotensin-aldosterone-system (RAAS) plays an important role in atrial fibrillation (AF). Evidence shows that blocking the RAAS with angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) has a definite role in preventing new onset AF and in maintaining sinus rhythm in recurrent AF. Our aim was to determine if ACEI/ARB treatment was associated with clinical outcomes [stroke/systemic embolic events (SEE), mortality] in a controlled, anticoagulated AF population. METHODS: An ancillary retrospective cross-sectional and longitudinal analysis of participants in the Stroke Prevention using an ORal Thrombin Inhibitor in AF (SPORTIF) III and V trials, in relation to use (or nonuse) of ACEI/ARBs. RESULTS: Rates of stroke/SEEs, mortality or major bleeding were no different between users and nonusers in the whole cohort, or in relation to the presence/absence of hypertension, coronary artery disease and previous stroke/transient ischaemic attack, nor amongst those aged <75 years. Patients aged > or = 75 years taking ACEIs or ARBs had lower mortality (HR 0.71, 95% CI 0.52-0.95), but no significant influence on other end-points was noted. Diabetics and those with left ventricular dysfunction on ximelagatran had a higher odds ratio of abnormal liver enzyme levels. There was no apparent benefit of ACEIs or ARBs on other event rates. CONCLUSIONS: This analysis from two large randomized trials of anticoagulation has not demonstrated a significant benefit of ACEI or ARB use amongst AF patients, except amongst elderly subjects.     

苯那普利、缬沙坦对糖尿病大鼠肾脏紧张素转换酶2表达的影响

目的 观察糖尿病大鼠肾脏血管紧张素转换酶2(ACE2)的表达及苯那普利、缬沙坦对糖尿病大鼠肾脏ACE2表达水平的影响,初步探讨ACE2在糖尿病肾病发病机制中的作用.方法 3月龄的SD雄性大鼠,腹腔内注射链脲佐菌素建立糖尿病大鼠模型,随机分为3组,每组7只,分别为糖尿病模型组、苯那普利治疗组[10 mg/(kg·d)]、缬沙坦治疗组[10 mg/(kg·d)],SD雄鼠7只作为正常对照组.给药3月后,处死动物、留取标本,反转录-聚合酶链式反应(RT-PCR)法测定肾脏中ACE和ACE2 mRNA的表达水平,免疫组化法比较肾脏中ACE2蛋白的表达水平.结果 与正常对照组相比,糖尿病模型组大鼠ACE、ACE2 mRNA表达分别下降30.7%、50.1%(P＜0.05).与糖尿病模型组比较,苯那普利组ACE mRNA的表达明显增加(P＜0.01),ACE2 mRNA的表达无明显差异;缬沙坦组ACE mRNA的表达治疗后没有明显变化,而ACE2 mRNA和蛋白的表达均有明显增加,分别增加68.7%和69.8%(P＜0.01).结论 1)肾脏局部ACE2表达水平的降低可能是糖尿病大鼠肾损害的发病机制之一;2)ARB可能是通过增加肾脏局部ACE2的表达而发挥肾脏保护作用.     

维持性血液透析患者透析前后血钾状态及其影响因素分析

目的观察维持性血液透析（MHD）患者透析前后血清钾离子浓度,并探讨影响其变化的临床因素。方法57例维持性血液透析患者,根据其是否服用血管紧张素转换酶抑制剂（ACEI）或血管紧张素Ⅱ受体拮抗剂（ARB）,将患者分为ACEI组、ARB组及非ACEI／ARB组;记录各组患者残余尿量及有无高钾血症临床表现,并取透析前后静脉血,测定血清钾、尿素氮（BUN）、血肌酐（SCr）、二氧化碳结合力（CO2CP）等指标,分析各组患者血钾浓度变化的差异及血钾浓度与其他临床因素之间的相关性。结果透析前高钾血症发生率36．8％（21／57）,其中76．2％（16／21）患者无高钾血症的临床表现;ACEI组、ARB组、非ACEI／ARB组透析前血钾水平分别为（6．0±0．95）mmol／L、（5．60±0．25）mmol／L、（4．72±0．95）mmol／L,其中ACEI组与其他2组之间差异有统计学意义（P〈0．01）,而ARB组与非ACEI／ARB组患者透析前血钾浓度差异无统计学意义（P〉0．05）;透析前血钾离子浓度与SCr、BUN浓度显著正相关（r=0．415、0．522,均P〈0．01）,但与患者残余尿量和透析前后CO2CP浓度变化无明显相关（r=0．559、0．411,均P〉0．05）。结论MHD患者透析前高钾血症发病率高,临床表现较隐匿,易被忽视;残余尿量并非判断患者是否易出现透析前高钾血症的可靠指标;增加透析次数,减量或停服ACEI,限制饮食中钾摄入是防治透析前高钾血症的有效方法。     

贝那普利联合缬沙坦对糖尿病肾病患者血清MCP-1及hs—CRP的影响

【目的】探讨贝那普利联合缬沙坦治疗2型糖尿病肾病（DN）对患者血清单核细胞趋化蛋白-1（MCP-1）及超敏C反应蛋白（hsCRP）的影响。【方法】选择本院临床确诊为DN的53例患者分为常规组（n=20）、贝那普利联合缬沙坦治疗组（联合组,n=33）,另设20例健康体检者作为正常对照组（对照组,n=20）,常规组患者给予常规治疗,联合组在常规组治疗基础上加用贝那普利5mg／d、缬沙坦80mg／d,观察6个月,采用双抗体夹心酶联吸附法（ELISA）测定两组患者治疗前后及对照组血清MCP-1及尿微量白蛋白（mA1b）,生化分析仪检测血肌酐（SCr）、血糖（FBG）、糖化血红蛋白（HbA1c）、hs-CRP。相关分析MCP-1与FBG、HbA1c、SCr、hs—CRP及尿mA1b之间的关系。【结果】①治疗前常规组、联合组患者血清SCr、MCP—1、hsCRP、FBG、HbA1c升高,皆显著高于对照组（P〈0．01）;治疗后,两组上述指标较治疗前不同程度下降（P〈0．05、0．01）;联合组降低幅度显著高于常规组（P〈0．05）。②相关分析表明血浆MCP-1水平与SCr、HbA1c及尿mA1b呈显著负相关（r=-0．74、-0．69、-0．75,P〈0．05、0．01）;与hsCRP呈显著正相关（r=0．88,P〈0．01）。【结论】贝那普利联合缬沙坦治疗可通过抑制DN患者的炎症反应起到肾脏保护作用。     

急性冠状动脉综合征低/高危人群血管紧张素转换酶基因插入/缺失多态性分析

目的 探讨ACE基因插入/缺失(I/D)多态性在急性冠状动脉综合征低/高危人群发病中的作用.方法 根据apoB、BMI将169例急性冠状动脉综合征(ACS)患者及94例正常健康人分为低危和高危人群,利用多聚酶反应(PCR)方法对这些患者的血管紧张素转换酶(ACE)基因插入/缺失多态性变异进行对比分析.结果ACS患者ACE基因DD型及D等位基因频率明显高于对照组(DD,0.385:0.213.P<0.05;D,0.583:0.441,P相似文献