Angiotensin-converting Enzyme Inhibitor Therapy Research Articles

Phosphodiesterase Type 5 Inhibition Reduces Albuminuria in Subjects with Overt Diabetic Nephropathy.

Diabetic nephropathy (DN) is the leading cause of ESRD worldwide. Reduced bioavailability or uncoupling of nitric oxide in the kidney, leading to decreased intracellular levels of the nitric oxide pathway effector molecule cyclic guanosine monophosphate (cGMP), has been implicated in the progression of DN. Preclinical studies suggest that elevating the cGMP intracellular pool through inhibition of the cGMP-hydrolyzing enzyme phosphodiesterase type 5 (PDE5) might exert renoprotective effects in DN. To test this hypothesis, the novel, highly specific, and long-acting PDE5 inhibitor, PF-00489791, was assessed in a multinational, multicenter, randomized, double-blind, placebo-controlled, parallel group trial of subjects with type 2 diabetes mellitus and overt nephropathy receiving angiotensin converting enzyme inhibitor or angiotensin receptor blocker background therapy. In total, 256 subjects with an eGFR between 25 and 60 ml/min per 1.73 m2 and macroalbuminuria defined by a urinary albumin-to-creatinine ratio >300 mg/g, were randomly assigned 3:1, respectively, to receive PF-00489791 (20 mg) or placebo orally, once daily for 12 weeks. Using the predefined primary assessment of efficacy (Bayesian analysis with informative prior), we observed a significant reduction in urinary albumin-to-creatinine ratio of 15.7% (ratio 0.843; 95% credible interval 0.73 to 0.98) in response to the 12-week treatment with PF-00489791 compared with placebo. PF-00489791 was safe and generally well tolerated in this patient population. Most common adverse events were mild in severity and included headache and upper gastrointestinal events. In conclusion, the safety and efficacy profile of PDE5 inhibitor PF-00489791 supports further investigation as a novel therapy to improve renal outcomes in DN.

Plasma oxidative stress level of IgA nephropathy in children and the effect of early intervention with angiotensin-converting enzyme inhibitors.

Aim:The purpose of this study was to investigate the change of the plasma oxidative stress level in children with IgA nephropathy (IgAN) and analyze its relativity to the clinical and pathological classification. To discuss the early effects of angiotensin-converting enzyme inhibitors (ACEIs) on the plasma oxidative stress level in children with IgA nephropathy.Methods:Thirty-eight children with IgAN were divided into groups according to their clinical features, pathologic grades, and treatments. Twenty healthy children were included in the control group.Results:The plasma level of advanced oxidation protein products (AOPPs), malonaldehyde (MDA), and superoxide dismutase (SOD) were detected. The plasma level of oxidative stress was significantly increased in the IgAN group, including a higher plasma level of AOPP and MDA and a lower plasma level of SOD. After treatment, the plasma level of oxidative stress was significantly decreased in the ACEI group.Conclusions:The children with IgAN had an increase in the plasma level of oxidative stress, expressed as an increased plasma level of AOPP and MDA and a decreased plasma level of SOD. Oxidative stress was associated with the progression of IgAN in children. Early treatment with ACEI therapy can significantly reduce the plasma level of oxidative stress in children with IgAN.

The Role of Medical Therapy in Moderate to Severe Degenerative Mitral Regurgitation

Mitral regurgitation (MR) is a common valvular disorder that has important health and economic consequences. Standardized guidelines exist regarding when and in whom to perform mitral valve surgery, but little information is available regarding medical treatment of MR. Many patients with moderate or severe MR do not meet criteria for surgery or are deemed to be at high risk for surgical therapy. We reviewed the available published data on medical therapy in the treatment of patients with primary MR. b-blockers and renin-angiotensin-aldosterone system inhibitors had the strongest supporting evidence for providing beneficial effects. b-blockers appear to lessen MR, prevent deterioration of left ventricular function, and improve survival in asymptomatic patients with moderate to severe primary MR. Angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy reduces MR, especially in asymptomatic patients. However, in the setting of hypertrophic cardiomyopathy or mitral valve prolapse, vasodilators can increase the severity of MR. To define the precise role of medical therapy, a larger randomized controlled trial is needed to confirm benefit and assess in which subsets of patients medical therapy is most useful. Medical therapy in some patients improves symptoms, lessens MR, and may delay the need for surgical intervention.

Simultaneous subacute coronary artery stent thrombosis in a carrier of two CYP2C19 loss–of function polymorphisms (*2/*3)

Simultaneous subacute coronary artery stent thrombosis in a carrier of two CYP2C19 loss–of function polymorphisms (*2/*3)

Neprilysin inhibition with sacubitril/valsartan in the treatment of heart failure: mortality bang for your buck.

Heart failure remains a leading cause of morbidity and mortality worldwide. Advanced therapies have prolonged survival in patients with advanced heart failure, but pharmacotherapeutic optimization remains the mainstay of treatment. It has been over 10 years since the last mortality-reducing medication has been approved by the Food and Drug Administration. This article reviews the background, current knowledge and data supporting the use of sacubitril/valsartan (Entresto(®) ), the newly FDA-approved medication that dually inhibits angiotensin and neprilysin, in the treatment of heart failure. A literature search was performed (January 1980 to August 2015) using PubMed and the search terms were as follows: neprilysin inhibitor, heart failure, endopeptidase, natriuretic peptides, angiotensin, omapatrilat, LCZ696, valsartan and sacubitril. Peer-reviewed, published clinical trials, review articles, relevant treatment guidelines and prescribing information documents were identified and reviewed for relevance. Additionally, reference citations from publications identified were reviewed. The inhibition of endopeptidases has been an area of extensive study for the treatment of heart failure. Previously published literature with the endopeptidase inhibitor omapatrilat failed to demonstrate a sufficient balance between clinical efficacy and safety to justify its approval. Omapatrilat blocked three pathways that break down bradykinin, leading to high rates of angioedema. Sacubitril, on the other hand, is metabolized to a form that is highly selective for neprilysin without possessing activity for the other two peptidases, ACE and APP. The combination of sacubitril with valsartan in a single formulation offers the benefit of concurrent blockade of the renin angiotensin aldosterone system and the inhibition of neprilysin while minimizing angioedema risk. When compared to ACE inhibitor therapy in systolic heart failure patients, sacubitril/valsartan demonstrated reductions in all-cause mortality and hospitalization due to heart failure while maintaining a similar safety profile. A formulation that contains both sacubitril and valsartan was manufactured and approved by the FDA in July 2015 for the reduction of mortality and hospitalization in systolic heart failure patients. The new medication offers a potentially superior alternative to ACE inhibitor therapy in the management of systolic heart failure. The effects of treatment with sacubitril/valsartan in the setting of diastolic heart failure are currently under investigation in clinical trials.

Cardiovascular risk reduction in hypertension: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers. Where are we up to?

Previously, management of hypertension has concentrated on lowering elevated blood pressure. However, the target has shifted to reducing absolute cardiovascular (CV) risk. It is estimated that two in three Australian adults have three or more CV risk factors at the same time. Moderate reductions in several risk factors can, therefore, be more effective than major reductions in one. When managing hypertension, therapy should be focused on medications with the strongest evidence for CV event reduction, substituting alternatives only when a primary choice is not appropriate. Hypertension management guidelines categorise angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) interchangeably as first-line treatments in uncomplicated hypertension. These medications have different mechanisms of action and quite different evidence bases. They are not interchangeable and their prescription should be based on clinical evidence. Despite this, currently ARB prescriptions are increasing at a higher rate than those for ACEI and other antihypertensive classes. Evidence that ACEI therapy prevents CV events and death, in patients with coronary artery disease or multiple CV risk factors, emerged from the European trial on reduction of cardiac events with perindopril in stable coronary artery disease (EUROPA) and Heart Outcomes Prevention Evaluation (HOPE) trials respectively. The consistent benefit has been demonstrated in meta-analyses. The clinical trial data for ARB are less consistent, particularly regarding CV outcomes and mortality benefit. The evidence supports the use of ACEI (Class 1a) compared with ARB despite current prescribing trends.

Use of ACE inhibitors in Fontan: Rational or irrational?

BackgroundDespite a lack of evidence supporting the use of angiotensin-converting enzyme (ACE) inhibitors in patients with a Fontan circulation, their use is frequent. We decided to identify the rationale for ACE inhibitor therapy in patients within the Australia and New Zealand Fontan Registry. MethodsAll patients in the Registry taking an ACE inhibitor at last follow up were identified, and a review of medical records was undertaken to determine the rationale for treatment initiation and reasons for treatment continuation or dose increase. ResultsIn 2015, 36% of the surviving patients in the Registry (462/1268) were taking an ACE inhibitor. Indications for initiation of therapy were ventricular systolic or diastolic dysfunction (29%), atrioventricular valve regurgitation (19%), preservation of normal ventricular function (7%), prolonged effusions at Fontan (6%), hypertension (6%), other (6%) and unknown (2%). No indication was stated in the remaining patients (25%). Those with hypoplastic left heart syndrome were more likely to be on an ACE inhibitor than those with an alternative primary morphology (70% vs 32%; p<0.001). Only 36% of the patients treated with an ACE inhibitor at last follow up (166/462) had an indication that would generally justify treatment in a two-ventricle circulation. ConclusionIt is likely that the use of ACE inhibitors in patients with a Fontan circulation is excessive within our region. The coordination of prospective, multicentre studies and initiatives such as the Australia and New Zealand Fontan Registry will facilitate further investigations to guide treatment decisions in the growing Fontan population.

Acute Hypotensive Transfusion Reaction in a Patient Taking Angiotensin Converting Enzyme Inhibitors Therapy: A Case Report and Literature Review

Acute Hypotensive Transfusion Reaction in a Patient Taking Angiotensin Converting Enzyme Inhibitors Therapy: A Case Report and Literature Review

Clinical efficacy of medicinal treatment in 15 children with Dent disease

Objective To investigate the drug effect of children with Dent disease who received therapy of potassium citrate and thiazide diuretics and angiotensin-converting enzyme inhibitors(ACEI), and to provide the refe-rence for the clinical treatment. Methods Dent disease patient who were followed-up in Bayi Children's Hospital Affiliated to Beijing Military Region General Hospital during the period of July 2006 and March 2014 were selected.The patients were administered a therapy of potassium citrate associated with thiazide diuretics and ACEI according to the level of proteinuria and calciuria and serum potassium.The underlying changes before and after the treatment were compared and analyzed. Results In 15 children with Dent disease, they were all male cases, onset age ranged from 3 months to 11 years old[(2.62±3.11)years old], and the disease duration ranged from 0.50 to 9.50 years old[(2.81±2.34)years]. The patients were followed up for 0.50 to 7.50 years[(3.61±2.62)years]. There was a significantly statistical difference in calcium/creatinine and daily Ca-creat ratio in contrast to before treatment[(0.41±0.19) mg/mg vs(0.26±0.12) mg/mg, t=2.603, P=0.021; (6.76±2.0) mg/kg vs (4.34±1.97) mg/kg, t=5.265, P=0.000], there was no significantly statistical difference in 24-hour urinary protein quantity in contrast to before treatment[(0.96±0.62) g/24 h vs (0.87±0.44) g/24 h, t=1.016, P=0.327]. One case with kidney stone and 5 cases with nephrocalcinosis had a negative result of renal ultrasound after treatment. Conclusions Treatment of potassium citrate combination with thiazide diuretics and ACEI can significantly decrease urinary calcium excretion, make a disappearance of kidney stone and nephrocalcinosi, and it may have a role in protecting renal function.Treatment of benazepril can not significantly decrease the proteinuria and has no substantial improvement in low molecular weight protein urine. Key words: Dent disease; Hydrochlorothiazide; Potassium citrate; Angiotensin-converting enzyme inhibitors

ACE-Inhibition Benefit on Lung Function in Heart Failure is Modulated by ACE Insertion/Deletion Polymorphism

The benefit of angiotensin converting enzyme (ACE) inhibition in chronic heart failure (HF) is partially due to its effects on pulmonary function and particularly on lung diffusion, the latter being counteracted by acetylsalicylic acid (ASA). Tissue ACE activity is largely determined by an insertion/deletion (I/D) polymorphism resulting in three possible genotypes (DD, ID and II). It is not clear if ACE inhibitor therapy could exert different effects in these genotypes. The aim of the study was to understand whether I/D polymorphism interferes with ACE inhibitor's protection of the lungs in HF during acute fluid overload. 100 HF patients (left ventricular ejection fraction ≤40%) in stable clinical conditions, treated with enalapril but without ASA performed pulmonary function tests including lung diffusion (DLco) and its subcomponents, membrane diffusion (Dm) and capillary volume (Vcap), and a cardiopulmonary exercise test before and immediately after rapid infusion of 500cc saline. ACE I/D genotype prevalence was: DD=28, ID =55 and II=17 cases. No significant differences in major pulmonary function and exercise parameters were observed before saline infusion among ACE genotypes. After fluid challenge, DD patients presented a higher DLco and Dm reduction than ID and II (DLco -2.3±1.3 vs. -0.8±1.9 and -0.6±1mL/mmHg/min, p<0.0001 and p<0.01; Dm -7±5 vs. -3.2±7.4 and -1.3±5mL/mmHg/min, p<0.05, respectively) and a higher increase in VE/VCO2 slope than II (1.8±1.9 vs. -0.8±2.3, p=0.01). ACE DD genotype is associated with higher vulnerability of the alveolar-capillary membrane to acute fluid overload in HF patients treated with ACE inhibitors.

Pickering Syndrome precipitated by Angiotensin Converting Enzyme Inhibitor

Pickering syndrome is an under recognised cardio-renal syndrome where life threatening flash pulmonary edema develops in the setting of diastolic dysfunction of the heart. Renal artery stenosis induced activation of sympathetic nervous system and renin-angiotensin-aldosterone system result in fluid retention; such fluid retention in the setting of diastolic dysfunction results in flash pulmonary edema. Most patients who present with pickering syndrome have normal coronary circulation and left ventricular systolic function. We here present a case of pickering syndrome that was precipitated by initiation of angiotensin converting enzyme inhibitor therapy in a patient with undiagnosed unilateral renal artery stenosis. The incidence of flash pulmonary edema decreases on revascularization of renal artery stenosis. Underlying renal artery stenosis should be suspected in a patient with recurrent flash pulmonary edema as such patients merit from revascularization of renal artery stenosis. To the best of our knowledge we are the first to report angiotensin converting enzyme inhibitors as a precipitator of pickering syndrome.

Blinding Them With Science? Evidence-Based Medicine as a Barrier to Health Care Value.

T he term ‘‘evidence-based medicine’’ (EBM) was introduced in 1992 in a seminal paper by Gordon Guyatt as a solution to ‘‘an exploding volume of literature . . . deepening concern about burgeoning medical costs, and increasing attention to quality and outcomes.’’ Over the ensuing decades, EBM has been integrated into the medical culture and incorporated almost universally into medical school and residency curricula. In addition, Guyatt’s recognition of the need to reduce health care costs and improve quality has entered the mainstream consciousness, framed increasingly around the notion of ‘‘value.’’ Value can be conceptualized as the ratio of health outcomes and costs. Skills in EBM are critical to optimizing value, since a deep understanding of evidence is required for predicting health outcomes in individual patients. In particular, clinicians must recognize the clinical impact of interventions, grapple with uncertainty in the evidence, and uncover bias in published studies in order to fully balance the benefits and harms of potential approaches. More than 20 years of EBM immersion should have thoroughly prepared us for these tasks—but has it? The study by Caverly et al in this issue of the Journal of Graduate Medical Education suggests that EBM education has failed to prepare physicians for high-value practice. The authors presented medical residents and attending internal medicine physicians with 4 vignettes that described drug studies with different types of endpoints: total mortality, diseasespecific mortality, a surrogate outcome (simply called a ‘‘risk factor’’ in the vignette), and a composite outcome with a surrogate component. Participants were asked to rate the extent to which each study proved that the new drug ‘‘might help people.’’ Improvement in the composite outcome, as proof of drug benefit, was rated most highly by both residents and attending physicians. While participants were not asked to directly compare endpoints, fewer than half rated all-cause mortality as better proof of benefit than improvement in a surrogate endpoint, and fewer than a quarter of participants rated all-cause mortality as better proof than a composite endpoint. Despite limitations in this study approach, the findings suggest that physicians lack the skill to accurately weigh the relative importance of different types of endpoints in clinical trials, and they tend to overvalue surrogate and composite endpoints. The overvaluing of surrogate and composite endpoints threatens health care value, because improvements in surrogate endpoints may occur without improvement (or with worsening) of clinical outcomes. For example, class 1C antiarrhythmic agents were routinely prescribed to post-myocardial infarction patients with asymptomatic ventricular arrhythmias after myocardial infarction for arrhythmia suppression, until the Cardiac Arrhythmia Suppression Trial found that these drugs actually increased mortality compared to a placebo. Use of dual angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy for a variety of indications grew rapidly based on the possible benefit in surrogate outcomes (eg, proteinuria in nephropathy) until complications such as hypotension and hyperkalemia were clarified. In both of these cases, prescribing based on surrogate outcomes likely harmed large numbers of patients. Further, since pharmaceutical industry marketing is often based on surrogate outcomes, a failure of physicians to recognize the limitations of surrogate outcomes may facilitate successful industry marketing of new expensive (and possibly minimally effective) drugs, resulting in reduced value for patients. Why, despite EBM education, are physicians unable to appreciate the greater value of a reduction in mortality compared to an improvement in a surrogate outcome? First, evaluating the appropriateness of endpoints is not adequately emphasized in EBM education. Despite the ubiquitous ‘‘PICO’’ structure for clinical questions, with ‘‘O’’ representing the outcome of interest, there is little instruction in the relative weight of different outcomes, and the complexity of composite outcomes defies simple explanation. Instruction in the applicability of evidence to patient care includes consideration of whether all clinically relevant outcomes were reportDOI: http://dx.doi.org/10.4300/JGME-D-15-00570.1

Sacubitril/valsartan (LCZ696) for the treatment of heart failure

ABSTRACTThe PARADIGM-HF study, a large outcome trial in heart failure and reduced ejection fraction (HFrEF), has recently shown improved cardiovascular outcomes with sacubitril/valsartan (Entresto®, Novartis), still commonly referred to as LCZ696, compared to ACE-inhibitor therapy, possibly leading us to a new era for heart failure (HF) treatment. LCZ696 represents a first-in-class drug acting through inhibition of angiotensin receptor and neprilysin, thus modulating the renin angiotensin aldosterone system and vasoactive substances such as natriuretic peptides. Based on the PARADIGM-HF results, the FDA recently approved LCZ696 as an effective means to reduce the burden of HF with reduced ejection fraction. Furthermore, these data also provided rationale to test LCZ696 in an ongoing trial with HF and preserved ejection fraction. Despite the enthusiasm regarding this novel compound, real world data on its efficacy and safety are eagerly expected. This article summarizes all evidences regarding LCZ696 and how to implement this new drug in the current HF armamentarium.

Can Pentoxifylline be used as Adjunct Therapy to ACE Inhibitors and ARBs in Preserving Kidney Function?

To determine if there is sufficient evidence to recommend the addition of pentoxifylline to standard ACE inhibitor and ARB therapy in chronic kidney disease patients to reduce proteinuria and preserve kidney function. A search of the literature was conducted using the PubMed.gov and ClinicalTrials.gov search engines and the search terms "pentoxifylline renoprotection", "pentoxifylline CKD", and "pentoxifylline nephropathy". RESULTS were limited to studies in human subjects and published in the English language. No date range was specified. Studies focused on the effects of pentoxifylline on drug induced nephropathy were excluded. Nine relevant articles were retrieved and evaluated. The two main populations studied were patients with chronic kidney disease (CKD) and patients with CKD and comorbid type 2 diabetes. Six of the nine studies reported a significant reduction in proteinuria in pentoxifylline treated patients. Four studies reported a significant change in estimated glomerular filtration rate (eGFR). Addition of pentoxifylline to ACE inhibitor and ARB therapy may improve proteinuria in CKD patients. There is conflicting evidence as to whether pentoxifylline will improve kidney function as measured by eGFR. pentoxifylline renoprotection, pentoxifylline CKD , pentoxifylline nephropathy.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Angioneuroticus oedema előfordulása ischaemiás stroke miatt rt-PA-val kezelt betegekben

Data of our 254 patients who were treated with rt-PA between 1st of Jan, 2011 and 31st of Dec, 2014 were processed. We focused on angioneurotic oedema as allergic complication of thrombolysis which caused life threatening respiratory obstruction in two cases. We describe these two patients' history. Out of 254 patients six (2.3%) suffered angioneurotic edema caused respiratory obstruction in two (0.90%) cases. This occurrence is approximately 1.3-5.1% in literature. Five, out of six patients who suffered from angioneurotic oedema, had been treated with ACE inhibitors or ARB before. The role of ACE inhibitors is known in metabolism of bradykinin cascade. Plasmin which present during thrombolysis, precipitates biochemical mechanisms of this potential life threatening complication. Therefore rt-PA alone can be the cause of angioedema, but it can be more frequent together with ACE inhibitors therapy.

Angiotensin-converting enzyme inhibitors as a cause of isolated angioedema in a Slovenian population.

Angioedema (AE) is a localized swelling of the subcutaneous tissue and mucosa. We aimed to identify how often AE is associated with angiotensin-converting enzyme inhibitor (ACEI-AE) therapy and whether the severity of AE episodes in these patients differs from the severity in idiopathic AE (IAE). We included patients with AE that were referred to a tertiary allergy clinic from 2005 to 2014. We obtained data on AE location, severity, number, and treatment of episodes from patient medical files. Patients treated with ACEI were contacted to obtain follow-up data on the effect of ACEI discontinuation. A total of 603 patients with AE were referred (59.9% women) to our clinic. A total of 36.9% had AE associated with urticaria or anaphylaxis. Among 381 patients with isolated AE, 10.5% of the patients were diagnosed with identified causes. The proportion of ACEI-AE was 27.1% to 37.9% (95% CI); others were classified as IAE. ACEI-AE cases had more severe episodes compared to IAE cases, which were more likely to be treated by a family doctor or even hospitalized. ACEI was shown to be the most frequent removable cause of isolated AE. About two-thirds of AE cases taking ACEI were resolved after removal of the drug.

Evaluation of subacute change in RAAS activity (as indicated by urinary aldosterone:creatinine, after pharmacologic provocation) and the response to ACE inhibition.

Objective:The objective of this study was to evaluate subacute changes in renin–angiotensin–aldosterone system (RAAS) activity during angiotensin-converting enzyme inhibitor (ACEI) therapy in dogs with experimental RAAS activation.Methods:Analysis of data (urine aldosterone:creatinine ratio (UAldo:C) and serum angiotensin-converting enzyme activity), in 31 healthy dogs with furosemide or amlodipine-activated RAAS that received an ACEI. When furosemide or amlodipine activation of RAAS preceded ACEI administration, incomplete RAAS blockade (IRB) was defined as a UAldo:C greater than (a) the dog’s ‘activated’ baseline value or (b) a population-derived cut-off value (mean + 2 SD (>1.0 μg/g) of pretreatment UAldo:C from our population of research dogs). In studies where RAAS activation occurred concurrently with ACEIs, IRB was defined as (a) a UAldo:C greater than either twofold the dog’s prestimulation baseline value or (b) 1.0 µg/g. Dogs were followed for 7–17 days.Results:Serum angiotensin-converting enzyme activity was measured in 19 dogs and was significantly reduced (P<0.0001) after ACEI administration. The overall incidence of IRB, when RAAS activation preceded ACEI administration, was 33% and 8% for definitions (a) and (b), respectively. The overall incidence of IRB, when ACEIs were concurrent with RAAS activation, was 65% and 61% for definitions (a) and (b), respectively.Conclusion:Increases in UAldo:C, despite ACEI administration, is evidence of IRB in this subacute model of experimental RAAS activation and suppression.

Angiotensin-converting enzyme inhibitor-associated angioedema treated with c1-esterase inhibitor: A case report and review of the literature.

Case Report:A 59-year old man currently on >5 years of angiotensin-converting enzyme inhibitor (ACEI) therapy presented to the emergency department with angioedema of the tongue and difficulty swallowing. After receiving conventional therapy of antihistamine, steroids, and epinephrine, the patient's condition continued to deteriorate, with imminent intubation. The patient was treated with a C1-esterase inhibitor (C1-INH) and experienced rapid resolution of symptoms, which avoided airway complications.Discussion:Although no therapy has been approved for the treatment of ACEI–associated angioedema (AAE), the conventional therapy (antihistamine, steroids, and epinephrine) often proves ineffective in this bradykinin-mediated angioedema. There are drugs approved and used for hereditary angioedema that may be effective in the acute phase of ACEI-AAE that may prevent the need for further interventions, such as intubation and tracheotomy. These drugs include icatibant, ecallantide, fresh frozen plasma, and C1-INH.Conclusion:The literature and clinical evidence indicate C1-INH can be effectively used in the treatment of ACEI-AAE to halt the progression of the condition, prevent airway compromise and the need for intervention, and lead to rapid resolution of symptoms.

Impact of Beta-blocker, ACE Inhibitor, and ARB therapy on thoracic aorta wall shear stress in bicuspid aortic valve patients

Impact of Beta-blocker, ACE Inhibitor, and ARB therapy on thoracic aorta wall shear stress in bicuspid aortic valve patients

Angiotensin-Converting Enzyme Inhibitors' Influence on Antiplatelet Therapy of Clopidogrel in ACS.

Clopidogrel is a prodrug, the minority of which is converted to an active metabolite by hepatic cytochrome P450 (CYP2C19), however, most of it is metabolized to inactive substance by hepatic carboxylesterase1 (CES1). Meanwhile angiotensin-converting enzyme inhibitors (ACEIs) are mostly metabolized by CES1. We aimed to assess the impact of ACEIs on platelet inhibition by clopidogrel. We genotyped variants CES1, CYP2C19*2 and *3 in 502 patients with acute coronary syndrome (ACS) receiving clopidogrel therapy, and analyzed the effects of ACEIs on responsiveness to clopidogrel by the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay and ADP-stimulated impedance whole blood platelet aggregation assay. It showed that the allele frequency of CES1 c.428A was 0% in these patients. 45.22% (227/502) of these patients were carriers of CYP2C19*2 or CYP2C9*3 loss-of-function alleles. Among them, 57.71% (131/227) of the patients with CYP2C19 variants received ACEIs therapy. In a total of 502 patients, there was no difference in the VASP-PRI or the impedance whole blood platelet aggregation assay between the ACEIs group and non-ACEIs group [56.26 ± 14.55% versus 57.76 ± 13.56%, p = 0.241; 0 (0 - 2) Ω vs. 0 (0 - 2) Ω, p = 0.856]. In the CYP2C19 variant patients, there was no difference in the VASP-PRI or the impedance whole blood platelet aggregation assay between ACEIs group and non-ACEIs group [57.24 ± 15.12% versus 58.07 ± 13.90%, p = 0.667; 0 (0 - 2) Ω versus 0 (0 - 2) Ω, p = 0.536]. In the subgroups of ACS patients (unstable angina, non-ST-segment elevation myocardial infarction, ST-segment elevation myocardial infarction), there was no difference in the VASP-PRI between the ACEIs group and non-ACEIs group [55.81 ± 15.24% versus 58.37 ± 13.31%, p = 0.103; 55.76 ± 15.20% versus 49.09 ± 15.22%, p = 0.098; 58.13 ± 11.48% versus 61.87 ± 10.34%, p = 0.221], and there was no difference in the impedance whole blood platelet aggregation assay between ACEIs group and non-ACEIs group [0 (0 - 2) Ω versus 0 (0 - 2) Ω, p = 0.936; 0 (0 - 2) Ω versus 0 (0 - 2) Ω, p = 0.625; 0 (0 - 1.25) Ω versus 0 (0 - 1.5) Ω, p = 0.788]. In our study, when ACEIs were used with clopidogrel, platelet response to clopidogrel was not affected. These findings suggest that the drug interaction between clopidogrel and ACEI is of little relevance in platelet function.