scholarly journals The effect of angiotensin-converting enzyme inhibitors on clinical outcomes in patients with ischemic cardiomyopathy and midrange ejection fraction: a post hoc subgroup analysis from the PEACE trial

2018 ◽  
Vol 12 (12) ◽  
pp. 351-359 ◽  
Author(s):  
Talal Alzahrani ◽  
John Tiu ◽  
Gurusher Panjrath ◽  
Allen Solomon
Keyword(s):  
Ejection Fraction ◽  
Angiotensin Converting Enzyme ◽  
Clinical Outcomes ◽  
Ace Inhibitors ◽  
Subgroup Analysis ◽  
Ischemic Cardiomyopathy ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
All Cause Mortality ◽  
Post Hoc

Background: There have been significant advances in the treatment of patients with cardiomyopathy with reduced ejection fraction (EF < 40%). However, there is a dearth of information in the treatment of patients with cardiomyopathy and midrange EF (40–50%). Current guidelines state to treat these patients similarly to patients with cardiomyopathy and preserved EF. Data from the Prevention of Events with Angiotensin-Converting Enzyme Inhibition (PEACE) trial were used to elucidate whether angiotensin-converting enzyme (ACE) inhibitors improve clinical outcomes in patients with ischemic cardiomyopathy and midrange EF. Methods: A post hoc subgroup analysis of the PEACE trial was conducted to evaluate the effect of ACE inhibitors in a subgroup of patients with ischemic cardiomyopathy and midrange EF (40–50%). A Chi-square test and a Student‘s t-test were used to examine and compare the binary and continuous variables of baseline characteristics and outcomes between experimental and comparison groups. Results: We studied a subgroup of patients from the PEACE trial with ischemic cardiomyopathy and midrange EF ( n = 2512 of 8290 total patients). Patients were assigned to either the interventional group ( n = 1247) or the placebo group ( n = 1265). There were no significant differences in baseline demographic and health characteristics between the two groups. During a total of 7 years (mean 4.7 years) of follow up, the risk of composite outcomes [all-cause mortality, nonfatal myocardial infarction, and stroke; relative risk (RR) 0.79, 95% confidence interval (CI) 0.63–0.98; p = 0.03] and all-cause mortality (RR 0.85, 95% CI 0.73–0.99; p = 0.03) was reduced in patients treated with trandolapril. Conclusion: This study revealed the benefit of ACE inhibitors among patients with ischemic cardiomyopathy and midrange EF.

Effects of angiotensin-converting enzyme inhibition on mitochondrial number in the aging mouse

1993 ◽  
Vol 265 (1) ◽  
pp. C15-C18 ◽  
Author(s):  
L. Ferder ◽  
F. Inserra ◽  
L. Romano ◽  
L. Ercole ◽  
V. Pszenny
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
Natural Aging ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
Group A ◽  
Aging Mechanisms ◽  
Mitochondrial Number ◽  
Group B ◽  
Kidney Liver

To investigate the effects of angiotensin-converting enzyme (ACE) inhibitors on the cellular function and structure in a variety of organs during the aging process, one hundred CF1 mice were divided into four groups of 25 animals each. Groups A, B, and C received enalapril in drinking water from weaning until the age of 24 mo. Doses administered were (in mg/l): group A, 20; group B, 10; group C, 5. Group D is the control. Animals were killed, and morphometric studies were performed in heart, kidney, liver, and spleen. As a result, there was a decrease of renal and myocardial sclerosis and an increase in the number of mitochondria in heart and liver cells, which is associated with a significant increase in survival of animals receiving ACE inhibitors. These findings lead us to think that natural aging mechanisms have been altered in those animals.

Angiotensin-converting enzyme inhibition, intracellular Na+, and Na(+)-K+ pumping in cardiac myocytes

1995 ◽  
Vol 268 (2) ◽  
pp. C366-C375 ◽  
Author(s):  
L. C. Hool ◽  
D. W. Whalley ◽  
M. M. Doohan ◽  
H. H. Rasmussen
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
Ace Inhibitor ◽  
Cardiac Mass ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
Intracellular Na Activity ◽  
Pump Activity ◽  
Converting Enzyme Inhibition ◽  
The Difference

Angiotensin-converting enzyme (ACE) inhibitors can reduce cardiac mass in both clinical and experimental cardiac hypertrophy. Because cytoplasmic Na+ and pH have been implicated as regulators of cell growth, we examined the effect of treatment with an ACE inhibitor on intracellular Na+ activity (alpha iNa) and pH (pHi) in the heart. After treatment of rabbits with captopril for 8 days alpha iNa was reduced relative to controls (3.6 +/- 0.4, n = 8, vs. 8.2 +/- 0.4 mM, n = 9, P < 0.001), whereas pHi was unchanged. To account for the difference in alpha iNa we measured electrogenic Na(+)-K+ pump activity in single isolated myocytes. Treatment with captopril increased pump currents at near-physiological levels of intracellular Na+ but had no effect at near-saturating levels of Na+. A similar increase in Na(+)-K+ pump activity occurred in rabbits treated with another ACE inhibitor, enalapril, but not with the vasodilator, hydralazine. We speculate that a decrease in alpha iNa after treatment with captopril may contribute to the well-documented ability of ACE inhibitors to reduce cardiac mass.

Structural basis for the C-domain-selective angiotensin-converting enzyme inhibition by bradykinin-potentiating peptide b (BPPb)

2019 ◽  
Vol 476 (10) ◽  
pp. 1553-1570 ◽  
Author(s):  
Edward D. Sturrock ◽  
Lizelle Lubbe ◽  
Gyles E. Cozier ◽  
Sylva L.U. Schwager ◽  
Afolake T. Arowolo ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Domain Structure ◽  
Ace Inhibitors ◽  
Ace Inhibition ◽  
Site Directed Mutagenesis ◽  
Structural Basis ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
X Ray Crystallography

Abstract Angiotensin-converting enzyme (ACE) is a zinc metalloprotease best known for its role in blood pressure regulation. ACE consists of two homologous catalytic domains, the N- and C-domain, that display distinct but overlapping catalytic functions in vivo owing to subtle differences in substrate specificity. While current generation ACE inhibitors target both ACE domains, domain-selective ACE inhibitors may be clinically advantageous, either reducing side effects or having utility in new indications. Here, we used site-directed mutagenesis, an ACE chimera and X-ray crystallography to unveil the molecular basis for C-domain-selective ACE inhibition by the bradykinin-potentiating peptide b (BPPb), naturally present in Brazilian pit viper venom. We present the BPPb N-domain structure in comparison with the previously reported BPPb C-domain structure and highlight key differences in peptide interactions with the S4 to S9 subsites. This suggests the involvement of these subsites in conferring C-domain-selective BPPb binding, in agreement with the mutagenesis results where unique residues governing differences in active site exposure, lid structure and dynamics between the two domains were the major drivers for C-domain-selective BPPb binding. Mere disruption of BPPb interactions with unique S2 and S4 subsite residues, which synergistically assist in BPPb binding, was insufficient to abolish C-domain selectivity. The combination of unique S9–S4 and S2′ subsite C-domain residues was required for the favourable entry, orientation and thus, selective binding of the peptide. This emphasizes the need to consider factors other than direct protein–inhibitor interactions to guide the design of domain-selective ACE inhibitors, especially in the case of larger peptides.

Angiotensin Converting Enzyme Inhibitor Dialyzability and Outcomes in Older Patients Receiving Hemodialysis

2015 ◽  
Vol 40 (3) ◽  
pp. 232-242 ◽  
Author(s):  
Matthew A. Weir ◽  
Jamie L. Fleet ◽  
Stephanie N. Dixon ◽  
Arsh K. Jain ◽  
Matthew Oliver ◽  
...  
Keyword(s):  
Relative Risk ◽  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
Older Patients ◽  
Primary Outcome ◽  
Ace Inhibitor ◽  
Enzyme Inhibitor ◽  
Chronic Hemodialysis ◽  
Converting Enzyme ◽  
All Cause Mortality

Background/Aims: Some angiotensin converting enzyme (ACE) inhibitors are efficiently removed from circulation by hemodialysis (‘high dialyzability'), whereas others are not (‘low dialyzability'). In patients receiving hemodialysis, this may influence the effectiveness of ACE inhibitors. Methods: Using linked healthcare databases we identified older patients receiving chronic hemodialysis who filled new ACE inhibitor prescriptions. The low dialyzability group (n = 3,369) included fosinopril and ramipril. The high dialyzability group (n = 5,974) included enalapril, lisinopril, and perindopril. The primary outcome was all-cause mortality within 180 days of first ACE inhibitor prescription. Results: There were 361 deaths among 5,974 patients (6.0%) prescribed with low dialyzability ACE inhibitors and 179 deaths among 3,369 patients (5.3%) prescribed with high dialyzability ACE inhibitors (relative risk 1.1, 95% CI 0.9-1.3, p = 0.6). Conclusion: In this study of older patients receiving hemodialysis, the dialyzability of ACE inhibitors was not associated with mortality or cardiovascular outcomes.

scholarly journals Angiotensin converting enzyme inhibitors do not increase the risk of poor outcomes in COVID-19 disease. A multi-centre observational study

2020 ◽  
Vol 65 (4) ◽  
pp. 149-153 ◽  
Author(s):  
Khurram Shahzad Khan ◽  
Hamish Reed-Embleton ◽  
Jen Lewis ◽  
Pamela Bain ◽  
Sajid Mahmud
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
Enzyme Inhibitors ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Hospitalised Patients ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Randomised Controlled

Background and aims Hypertension is associated with an increased risk of severe outcomes with COVID-19 disease. Angiotensin Converting Enzyme (ACE) inhibitors are widely used as a first line medication for the treatment of hypertension in the UK, although their use was suggested in early reports to increase the risk associated with SARS-CoV-2 infection. Methods A prospective cohort study of hospitalised patients with laboratory confirmed COVID-19 was conducted across three hospital sites with patients identified on the 9th April 2020. Demographic and other baseline data were extracted from electronic case records, and patients grouped depending on ACE inhibitor usage or not. The 60-day all-cause mortality and need for intubation compared. Results Of the 173 patients identified, 88 (50.8%) had hypertension. Of these 27 (30.7%) used ACE inhibitors. We did not find significant differences in 60-day all-cause mortality, the requirement for invasive ventilation or length of stay between our patient cohorts after adjusting for covariates. Conclusion This study contributes to the growing evidence supporting the continued use of ACE inhibitors in COVID-19 disease, although adequately powered randomised controlled trials will be needed to confirm effects.

Use of Angiotensin-Converting Enzyme Inhibitors in Heart Failure

1994 ◽  
Vol 10 (4) ◽  
pp. 156-163 ◽  
Author(s):  
Bisrat Hailemeskel ◽  
Vlncent F. Mauro
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Ejection Fraction ◽  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
Current Data ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Reduced Ejection Fraction ◽  
English Language Journal

Objective: To review the literature discussing the use of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure. Data Sources: English-language journal articles. Study Selection: Representative articles discussing the effects of ACE inhibitors on hemodynamics, symptoms, and survival. Data Extraction: Studies selected for review in the text were based on study design and clinical endpoints. Data Synthesis: Heart failure results in a series of compensatory responses that, although effective acutely, are ultimately maladaptive. A major mediator in this process is angiotensin II. The production of angiotensin II is dependent on the ACE. Inhibition of this enzyme by ACE inhibitors results in fewer symptoms, improved hemodynamic function, and prolonged survival in patients with heart failure. Conclusions: ACE inhibitors are beneficial in improving the survival of patients with symptomatic heart failure and of patients who have recently had an acute myocardial infarction (MI) and subsequently have a reduced ejection fraction. There appears to be no advantage for immediately initiating ACE-inhibitor therapy within the first few hours of an MI episode. With respect to patients with a reduced ejection fraction without symptoms of heart failure, current data suggest that ACE inhibitors delay the onset of symptoms of heart failure, reduce the need for hospitalization, and may possibly improve survival.

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