Therapeutic efficacy and safety of ACE inhibitors in the hypertensive paediatric population: a review

Purpose: Since 1997, strong incentives have been introduced worldwide to improve access to safe and effective medicines addressing the therapeutic needs of children. ACE inhibitors, the most prescribed antihypertensive drugs in the paediatric population, are one of the prototype drugs targeted by the legislation initiatives. Our purpose in assembling this review is to evaluate and describe the current evidence for the efficacy and safety profile of ACE inhibitors in the paediatric population. Methods: The authors made a descriptive review of the literature from 1980 to 2015 using the following search terms: hypertension, child, paediatric, ACE (inhibitors), renin angiotensin aldosterone system, captopril, lisinopril, enalapril, ramipril and fosinopril. Results: A total of 16 studies evaluating efficacy and safety of ACE inhibitors were included in this review. The included studies demonstrate that ACE inhibitors have the potency to decrease the systolic and/or diastolic blood pressure with an overall favourable safety profile in a short-term period. More importantly, the incentives resulted in an improvement of the overall availability of paediatric labelling, dosing and safety information for ACE inhibitors. However, they failed to fulfil several of paediatric needs: absence of long-term safety data on growth and maturation, absence of commercially available child-friendly formulations and incomplete evaluation of the entire paediatric hypertension population. Conclusion: Additional efforts are needed to close the gap between the availability of drugs that are labelled and indicated for paediatric use and the actual drug usage in children, especially in young children, neonates and children with severe hypertension, renal transplantation or severe renal impairment

Whey-derived peptides interactions with ACE by molecular docking as a potential predictive tool of natural ACE inhibitors

Several milk/whey derived peptides possess high in vitro angiotensin I-converting enzyme (ACE) inhibitory activity. However, in some cases, poor correlation between the in vitro ACE inhibitory activity and the in vivo antihypertensive activity has been observed. The aim of this study is to gain insight into the structure-activity relationship of peptide sequences present in whey/milk protein hydrolysates with high ACE inhibitory activity, which could lead to a better understanding and prediction of their in vivo antihypertensive activity. The potential interactions between peptides produced from whey proteins, previously reported as high ACE inhibitors such as IPP, LIVTQ, IIAE, LVYPFP, and human ACE were assessed using a molecular docking approach. The results show that peptides IIAE, LIVTQ, and LVYPFP formed strong H bonds with the amino acids Gln 259, His 331, and Thr 358 in the active site of the human ACE. Interestingly, the same residues were found to form strong hydrogen bonds with the ACE inhibitory drug Sampatrilat. Furthermore, peptides IIAE and LVYPFP interacted with the amino acid residues Gln 259 and His 331, respectively, also in common with other ACE-inhibitory drugs such as Captopril, Lisinopril and Elanapril. Additionally, IIAE interacted with the amino acid residue Asp 140 in common with Lisinopril, and LIVTQ interacted with Ala 332 in common with both Lisinopril and Elanapril. The peptides produced naturally from whey by enzymatic hydrolysis interacted with residues of the human ACE in common with potent ACE-inhibitory drugs which suggests that these natural peptides may be potent ACE inhibitors

Angiotensin-converting enzyme (ACE) I/D and bradykinin B2 receptor T/C genes polymorphism in patients with ACE inhibitors-related cough

Background: Angiotensin-converting enzyme (ACE) inhibitors-related cough had been reported to contribute for discontinuation of ACE inhibitors therapy. The role of ACE I/D and bradykinin B2 receptor T/C genes in ACE inhibitors-related cough is still unclear.Objectives: To determine ACE I/D and bradykinin B2 receptor T/C genes polymorphisms in patients with ACE-inhibitors-related cough.Subjects and methods: An analytical study with cross-sectional design was conducted at Saiful Anwar General Hospital from June 2013 to September 2014. We used the polymerase chain reaction to genotype ACE I/D and bradykinin B2 receptor T/C genes. Data on both ACE I/D and bradykinin B2 receptor T/C genes polymorphisms in cough and non cough group of hypertensive patients treated with ACE inhibitors in our Hospital during the period were analyzed using multiple logistic regression. Moreover, a metaanalysis was performed to summarize findings from other regions.Results: A total of 18 patients with cough (21%) and 67 patients without cough (79%) of hypertensive patients treated with ACE inhibitors from our Hospital during the period were analyzed for this study. In our population, no correlation was observed between ACE inhibitors-related cough and both ACE I/D (p = 0.560) and bradykinin B2 receptor T/C (p = 0.475) genes polymorphism. However, our meta-analysis of five studies consisting of 267 patients with cough and 346 patients without cough revealed that higher risk of ACE inhibitors-related cough was 1.82-fold associated with T allele of bradykinin B2 receptor T/C gene polymorphism (p = 0.0310).Conclusions: While the evidence in our meta-analysis suggests strong role for bradykinin gene polymorphism in ACE inhibitors-related cough, however, in our population, we did not find any association.Keywords: ACE inhibitors-related cough, ACE I/D gene polymorphism, Bradykinin B2 receptor T/C gene, polymorphism, Hypertensio

The EuroHeart Failure Survey programme—a survey on the quality of care among patients with heart failure in Europe Part 2: treatment

National surveys suggest that treatment of heart failure in daily practice differs from guidelines and is characterized by underuse of recommended medications. Accordingly, the Euro, Heart Failure Survey was conducted to ascertain how patients hospitalized for heart failure are managed in Europe and if national variations occur in the treatment of this condition. Methods The survey screened discharge summaries of 11 304 patients over a 6-week period in 115 hospitals from 24 countries belonging to the ESC to study their medical treatment. Results Diuretics (mainly loop diuretics) were prescribed in 86.9% followed by ACE inhibitors (61.8%), beta-blockers (36.9%), cardiac glycosides (35.7%), nitrates (32.1%), calcium. channel blockers (21.2%) and spironolactone (20.5%). 44.6% of the population used four or more different drugs. Only 17.2% were under the combination of diuretic, ACE inhibitors and beta-blockers. Important local variations were found in the rate of prescription of ACE inhibitors and particularly beta-blockers. Daily dosage of ACE inhibitors and particularly of beta-blockers was on average below the recommended target dose. Modelling-analysis of the prescription of treatments indicated that the aetiology of heart failure, age, co-morbid factors and type of hospital ward influenced the rate of prescription. Age 70 years, in patients with respiratory disease and increased in cardiology wards, in ischaemic heart failure and in mate subjects. Prescription of cardiac glycosides was significantly increased in patients with supraventricular tachycardia/atrial fibrillation. Finally, the rate of prescription of antithrombotic agents was increased in the presence of supraventricular arrhythmia, ischaemic heart disease, mate subjects but was decreased in patients over 70. Conclusion Our results suggest that the prescription of recommended medications including ACE inhibitors and beta-blockers remains limited and that the daily dosage remains tow, particularly for beta-blockers. The survey also identifies several important factors including age, gender, type of hospital ward, co morbid factors which influence the prescription of heart failure medication at discharge

The use of angiotensin-converting enzyme inhibitors in general medicine

Angiotensin-converting enzyme (ACE) inhibitors are a class of drugs commonly used in the management of hypertension, congestive heart failure, cerebrovascular disease, stable coronary heart disease and diabetes-associated nephropathy. ACE inhibitors are divided into three classes, namely sulphydryl-containing ACE inhibitors structurally related to captopril, carboxyl-containing ACE inhibitors structurally related to enalapril, and phosphorus-containing ACE inhibitors structurally related to fosinopril. Though these classes of drugs are important in the treatment of the above conditions, they are not without side-effects. It is very important for clinicians to be aware of these side-effects so that patients can be warned, and compliance can be improved

Low use of statins and other coronary secondary prevention therapies in primary and secondary care in India.

ObjectiveTo determine the frequency of use of pharmacotherapy with aspirin, beta blocker, statin, and angiotensin-converting enzyme (ACE) inhibitor in patients with stable coronary heart disease (CHD) among physicians at different levels of health care in Rajasthan state, India.MethodsPhysicians practicing at tertiary hospitals and clinics at tertiary, secondary and primary levels were contacted. Prescriptions of CHD patients were audited and descriptive statistics reported.ResultsWe evaluated 2,993 prescriptions (tertiary hospital discharge 711, tertiary 688, secondary 1,306, and primary 288). Use of aspirin was in 2,713 (91%) of prescriptions, beta blockers 2,057 (69%), ACE inhibitors or angiotensin receptor blockers (ARBs) 2,471 (82%), and statins 2,059 (69%). Any one of these drugs was prescribed in 2,991 (100%), any two in 2,880 (96%), any three in 1,740 (58%), and all four in 1,062 (35.5%) (P < 0.001). As compared to tertiary hospital, prescriptions at tertiary, secondary, and primary levels were lower: aspirin (96% vs 95%, 91%, 67%), beta blockers (80% vs 62%, 66%, 70%), statins (87% vs 82%, 62%, 21%): two drugs (98% vs 96%, 98%, 85%), three drugs (75% vs 58%, 55%, 28%), or four drugs (54% vs 44%, 28%, 7%) (P < 0.01). Use of ACE inhibitors/ARBs was similar while nitrates (43% vs 23%, 43%, 70%), dihydropyridine calcium channel blockers (12% vs 15%, 30%, 47%), and multivitamins (6% vs 26%, 37%, 47%) use was more in secondary and primary care.ConclusionsThere is suboptimal use of various evidence-based drugs (aspirin, beta blockers, ACE inhibitors, and statins) for secondary prevention of CHD in India

Pengaruh renoprotektif inhibitor angiotensin convering enzyme (ACE) pada progresivitas penyakit ginjal diabetik

Mochammad Sja\u27bani and I Gde Raka Widiana -- Renoprotective effects of ACE inhibitors on the progression of diabetic kidney disease Functional and structural abnormalities in diabetic kidney disease lead to intraglomerular hypertension and albuminuria. Systemic hypertension and genetically inherited defect on autoregulation in preglomerular arterioles will enhance kidney injury in those patients. ACE inhibitors could reduce albuminuria In patients with diabetic nephropathy and animal models. Hemodynamic improvement manifested by the reduction of albuminuria by ACE inhibitors is only seen in the experimental studies. However, recent studies have shown that ACE inhibitors, especially captopril, could give protective effects on kidneys in insulin-dependent diabetics with nephropathy. Captopril also reduces the risk of death, dialysis, and kidney transplantation in those patients. Key words: diabetes mellitus -- kidney disease -- ACE inhibitors -- albuminuria -- kidney preservatio

Influence of renin-angiotensin-aldosterone system inhibitors on plasma levels of angiotensin-converting enzyme 2

Concern has been raised that treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the expression of angiotensin-converting enzyme 2 (ACE2), which acts as the entry receptor for SARS-CoV-2, and lead to an increased risk of death from SARS-CoV-2. We aimed to address this concern by evaluating the in vivo relationship of treatment with ACE inhibitors and angiotensin receptor blockers (ARB) with circulating plasma concentrations of ACE2 in a large cohort of patients with established cardiovascular disease (n = 1864) or cardiovascular risk factors (n = 2144) but without a history of heart failure.; Angiotensin-converting enzyme 2 was measured in 4008 patients (median age 68, 33% women, 31% on ACE-inhibitors, 31% on ARB) using the SOMAscan proteomic platform (SomaLogic Inc, Colorado, USA). Plasma concentration of ACE2 was comparable in 1250 patients on ACE inhibitors (mean 5.99) versus patients without ACE inhibitors (mean 5.98, P = 0.54). Similarly, plasma concentration of ACE2 was comparable in 1260 patients on ARB (mean 5.99) versus patients without ARB (mean 5.98, P = 0.50). Plasma concentration of ACE2 was comparable in 2474 patients on either ACE inhibitors or ARB (mean 5.99) versus patients without ACE inhibitors or ARB (mean 5.98, P = 0.31). Multivariable quantile regression model analysis confirmed the lack of association between treatment with ACE inhibitors or ARB and ACE2 concentrations. Body mass index showed the only positive association with ACE2 plasma concentration (effect 0.015, 95% confidence interval 0.002 to 0.028, P = 0.024).; In a large cohort of patients with established cardiovascular disease or cardiovascular risk factors but without heart failure, ACE inhibitors and ARB were not associated with higher plasma concentrations of ACE2

Incidence of adverse events with telmisartan compared with ACE inhibitors: evidence from a pooled analysis of clinical trials

Telmisartan is indicated for the prevention of cardiovascular events in high-risk patients, based on comparable efficacy to the angiotensin-converting enzyme (ACE) inhibitor, ramipril, in the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET®) trial. However, tolerability must be considered when selecting treatments. This analysis compared the tolerability of telmisartan and ACE inhibitors using data pooled from 12 comparative, randomized studies involving 2564 telmisartan-treated patients and 2144 receiving ACE inhibitors (enalapril, lisinopril, or ramipril). Incidence rates of adverse events for the combined ACE inhibitor treatments and for telmisartan were similar (42.8% vs 43.9%, respectively) as were the rates of serious adverse events (1.8% vs 1.7% for telmisartan, respectively). Patients receiving ACE inhibitors had more cough (8.6% vs 2.6% with telmisartan, P < 0.0001). Results were similar irrespective of age, gender, or ethnicity. The adverse event of angioedema was observed in four patients (0.2%) receiving ACE inhibitors versus none with telmisartan (P = 0.043). There were small, numerical differences in serious adverse events. A total of 107 patients (5.0%) receiving ACE inhibitors and 93 patients (3.6%) receiving telmisartan discontinued treatment because of adverse events (P = 0.021); of these, 32.7% and 5.4%, respectively, were discontinuations due to cough (relative risk reduction of 88% [P < 0.0001] with telmisartan). Telmisartan and ACE inhibitors produced comparable blood pressure reductions at marketed doses. Telmisartan and ACE inhibitors are suitable for the prevention of cardiovascular events in high-risk patients, but telmisartan is better tolerated, particularly with regard to cough

Drug Pricing in the United States: A Comparison with Canada and Mexico

The purpose of this study was to assess prescription drug pricing in the United States compared with that in Canada and Mexico. The study was designed to focus on ACE inhibitors in order to gather a limited, yet meaningful outcome. Prices of eight ACE inhibitors and their generic equivalents were gathered for the United States, Canada, and Mexico via Walgreens and international online pharmacies, respectively. The differences in price per pill for Canada and Mexico when paired against the United States were analyzed using t statistics. The results indicate there is a significant price difference for brand name and generic ACE inhibitors in Canada and the United States. However, no significant cost difference was determined for brand name or generic ACE inhibitors in Mexico and the United States. Prices for brand name and generic ACE inhibitors in Canada were found to be lower than those in Mexico