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Pharmacological Research Apr 2020With ageing of the global society, the frequency of ageing-related neurodegenerative diseases such as Alzheimer`s disease (AD) is on the rise worldwide. Currently, there... (Review)
Review
With ageing of the global society, the frequency of ageing-related neurodegenerative diseases such as Alzheimer`s disease (AD) is on the rise worldwide. Currently, there is no cure for AD, and the four drugs approved for AD only have very small effects on AD symptoms. Consequently, there are enormous efforts worldwide to identify new targets for treatment of AD. Approaches that interfere with classical neuropathologic features of AD, such as extracellular senile plaques formed of aggregated amyloid-beta (Abeta), and intracellular neurofibrillary tangles of hyperphosphorylated tau have not been successful so far. In search for a treatment approach of AD, we found that inhibition of the angiotensin-converting enzyme (ACE) by a centrally acting ACE inhibitor retards symptoms of neurodegeneration, Abeta plaque formation and tau hyperphosphorylation in experimental models of AD. Our approach is currently being investigated in a clinical setting. Initial evidence with AD patients shows that a brain-penetrating ACE inhibitor counteracts the process of neurodegeneration and dementia. Moreover, centrally acting ACE inhibitors given in addition to the standard therapy, cholinesterase inhibition, can improve cognitive function of AD patients for several months. This is one of the most promising results for AD treatment since more than a decade.
Topics: Alzheimer Disease; Angiotensin-Converting Enzyme Inhibitors; Animals; Cognition; Disease Models, Animal; Humans; Peptidyl-Dipeptidase A; Receptor, Angiotensin, Type 1; Renin-Angiotensin System
PubMed: 30991105
DOI: 10.1016/j.phrs.2019.04.014 -
Journal of Managed Care Pharmacy : JMCP 2010Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are widely prescribed for the treatment of hypertension and heart failure, as...
BACKGROUND
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are widely prescribed for the treatment of hypertension and heart failure, as well as for kidney disease prevention in patients with diabetes mellitus and the management of patients after myocardial infarction.
OBJECTIVE
To (a) describe ACE inhibitor and ARB utilization and spending in the Medicaid fee-for-service program from 1991 through 2008, and (b) estimate the potential cost savings for the collective Medicaid programs from a higher ratio of generic ACE inhibitor utilization.
METHODS
A retrospective, descriptive analysis was performed using the National Summary Files from the Medicaid State Drug Utilization Data, which are composed of pharmacy claims that are subject to federally mandated rebates from pharmaceutical manufacturers. For the years 1991-2008, quarterly claim counts and expenditures were calculated by summing data for individual ACE inhibitors and ARBs. Quarterly per-claim expenditure as a proxy for drug price was computed for all brand and generic drugs. Market shares were calculated based on the number of pharmacy claims and Medicaid expenditures.
RESULTS
In the Medicaid fee-for-service program, ACE inhibitors accounted for 100% of the claims in the combined market for ACE inhibitors and ARBs in 1991, 80.6% in 2000, and 64.7% in 2008. The Medicaid expenditure per ACE inhibitor claim dropped from $37.24 in 1991 to $24.03 in 2008 when generics accounted for 92.5% of ACE inhibitor claims; after adjusting for inflation for the period from 1991 to 2008, the real price drop was 59.2%. Brand ACE inhibitors accounted for only 7.5% of the claims in 2008 for all ACE inhibitors but 32.1% of spending; excluding the effects of manufacturer rebates, Medicaid spending would have been reduced by $28.7 million (9%) in 2008 if all ACE inhibitor claims were generic. The average price per ACE inhibitor claim in 2008 was $24.03 ($17.64 per generic claim vs. $103.45 per brand claim) versus $81.98 per ARB claim. If the ACE inhibitor ratio had been 75% in 2008 rather than 64.7%, the Medicaid program would have saved approximately 13% or about $41.8 million, again excluding the effects of manufacturer rebates. If the ACE inhibitor ratio had been 90% in 2008, the cost savings for the combined Medicaid fee-forservice programs would have been about 33% or about $102.3 million. The total cost savings opportunity with 100% generic ACE inhibitor utilization in 2008 and an ACE inhibitor ratio of 75% was $75.1 million (24%) or $142.3M (46%) with a 90% ACE inhibitor ratio.
CONCLUSION
Factors that affect Medicaid spending by contributing to increased utilization of ACE inhibitors and ARBs, such as the rising prevalence of hypertension, heart disease, and diabetes, can be offset by reduction in the average price attained through a higher proportion of ACE inhibitors and a higher percentage of generic versus brand ACE inhibitors.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Drug Costs; Drug Utilization; Fee-for-Service Plans; Health Expenditures; Humans; Medicaid; Retrospective Studies; Time Factors; United States
PubMed: 21067253
DOI: 10.18553/jmcp.2010.16.9.671 -
Journal of Investigative Medicine High... 2021The patient is a 69-year-old male with a past medical history of intellectual disability, hypertension, type 2 diabetes mellitus, and angiotensin-converting enzyme (ACE)...
The patient is a 69-year-old male with a past medical history of intellectual disability, hypertension, type 2 diabetes mellitus, and angiotensin-converting enzyme (ACE) inhibitor-associated angioedema who presented to the emergency department with difficulty breathing. On physical examination, the patient had significant facial edema. Nasal fiber-optic visualization revealed extensive airway edema involving the supraglottic region and the arytenoids. The patient was successfully intubated through the collective teamwork of ENT, anesthesia, and critical care teams. He was managed in the intensive care unit until recovery. Workup for markers for allergic causes of angioedema were within normal limits. Further investigation revealed that symptoms developed following the initiation of a dipeptidyl peptidase 4 (DPP-IV) inhibitor. The angiotensin-converting enzyme and DPP-IV play a significant role in the metabolism of bradykinin and substance P to their inactive metabolites. The complex interplay between the enzymes in the high-molecular-weight kininogen (HWMK) system may increase the risk of angioedema in patients with a known history of ACE inhibitor-associated angioedema when placed on a DPP-IV inhibitor. This case report highlights the pathophysiology involved.
Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Humans; Male
PubMed: 34330175
DOI: 10.1177/23247096211033049 -
Clinical Cardiology Jun 1990Quinapril hydrochloride, a new, orally active, nonpeptide, nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor, has been studied extensively in a variety of in... (Review)
Review
Quinapril hydrochloride, a new, orally active, nonpeptide, nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor, has been studied extensively in a variety of in vitro and in vivo animal models. Quinapril inhibits the contractile and pressor effects of angiotensin I in rabbit aorta and in rats, respectively, and lowers blood pressure in both high- and normal-renin rodent and diuretic-treated dog models of hypertension. No tolerance to the antihypertensive effects of quinapril was noted in spontaneously hypertensive rats treated with quinapril for up to 14 consecutive days. As with other ACE inhibitors, quinapril had virtually no effect on the development of hypertension in the renin-independent one-kidney deoxycorticosterone (DOCA)-salt hypertensive rat. Antihypertensive activity best correlates with the inhibition of tissue (vascular) ACE, and thus the reduction in peripheral vascular resistance associated with plasma and tissue ACE most likely accounts for the therapeutic benefit of quinapril. Preliminary data from a trial of quinapril in cardiomyopathic hamsters show that the drug prevents the anticipated decline in left ventricular contractile function and retards the temporal progression of left ventricular failure. ACE inhibitors have been found to have a lipid-neutral profile, unlike some other classes of antihypertensives. Quinapril is rapidly absorbed and extensively distributed to all tissues except brain. It is rapidly hydrolyzed to quinaprilat, its pharmacologically active diacid form. Metabolism to other compounds is not extensive. Quinapril's preclinical toxicologic profile is similar to that of other ACE inhibitors. Long-term toxicology studies show that quinapril is not teratogenic, carcinogenic, or mutagenic.
Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Animals; Cricetinae; Drug Evaluation; Humans; Hypertension; Isoquinolines; Male; Quinapril; Rats; Rats, Inbred SHR; Tetrahydroisoquinolines
PubMed: 2189623
DOI: 10.1002/clc.4960131403 -
Medscape Journal of Medicine Mar 2008Blockade of the renin-angiotensin system (RAS) by angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) plays an important role in... (Meta-Analysis)
Meta-Analysis Review
Blockade of the renin-angiotensin system (RAS) by angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) plays an important role in the protection and prevention of cardiovascular disease. The Heart Outcomes Prevention Evaluation (HOPE) study established the significant effect of ACE inhibition on cardiovascular morbidity and mortality beyond blood pressure control. Smaller studies have demonstrated the efficacy of ARBs. In addition, a recent analysis from the Blood Pressure Lowering Treatment Trialists' Collaboration showed that ARB-based and ACE inhibitor-based treatment regimens were comparable in terms of the odds ratio for stroke and heart failure, independent of blood pressure reduction. There is an emerging body of evidence to suggest that a combination approach to RAS blockade with an ARB and an ACE inhibitor may further improve cardiovascular outcome compared with monotherapy with either agent alone. The large-scale ONgoing Telmisartan Alone or in combination with Ramipril Global Endpoint Trial (ONTARGET), comparing high-dose ramipril (HOPE study dosage) with telmisartan or a combination of the two, should provide important insight into the benefits of RAS blockade intervention. The results of ONTARGET are anticipated to be available in 2008.
Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Cardiovascular Diseases; Clinical Trials as Topic; Evidence-Based Medicine; Humans; Practice Guidelines as Topic; Treatment Outcome
PubMed: 18449379
DOI: No ID Found -
BMJ Case Reports Aug 2012Icatibant is a selective bradykinin 2 receptor antagonist, currently licensed for use in hereditary angioedema. Its benefit in ACE inhibitor angioedema is yet to be...
Icatibant is a selective bradykinin 2 receptor antagonist, currently licensed for use in hereditary angioedema. Its benefit in ACE inhibitor angioedema is yet to be fully established. A handful of preliminary case reports suggest that it may be of benefit in reducing both symptom severity and possible hospital or intensive care admission. To date, there are no case reports of the usage of Icatibant in the emergency department in the UK. Here we report our experience of Icatibant in a 62-year-old gentleman presenting with severe oral, pharyngeal and laryngeal oedema while on an ACE inhibitor.
Topics: Adrenergic beta-Antagonists; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Bradykinin B2 Receptor Antagonists; Epiglottis; Humans; Intubation, Intratracheal; Male; Middle Aged; Ramipril; Tongue; Vocal Cords
PubMed: 22936825
DOI: 10.1136/bcr-2012-006646 -
European Review For Medical and... Oct 2022The aim of the study was to review the literature on clinical pharmacology of lercanidipine and experimental and clinical evidence and evaluate its ability to reduce... (Review)
Review
OBJECTIVE
The aim of the study was to review the literature on clinical pharmacology of lercanidipine and experimental and clinical evidence and evaluate its ability to reduce proteinuria and preserve renal function when used as monotherapy or in combination with the angiotensin-converting enzyme (ACE) inhibitor enalapril.
MATERIALS AND METHODS
MEDLINE/PubMed was searched for appropriate keywords.
RESULTS
Lercanidipine, a third-generation calcium channel blocker, has been shown to have a unique pharmacological and clinical profile, which translates into favorable renal hemodynamic changes. The fixed-dose combination lercanidipine/enalapril has been proposed to overcome unmet therapeutic needs, often as the initial treatment in the high-risk patient.
CONCLUSIONS
Lercanidipine may be regarded as an ideal antihypertensive drug for patients at renal risk and possibly the preferred choice among calcium channel blocker drugs.
Topics: Humans; Antihypertensive Agents; Enalapril; Calcium Channel Blockers; Hypertension; Angiotensin-Converting Enzyme Inhibitors; Kidney; Blood Pressure
PubMed: 36314318
DOI: 10.26355/eurrev_202210_30018 -
ACE-inhibitor therapy at relatively high doses and risk of renal worsening in chronic heart failure.Arquivos Brasileiros de Cardiologia Dec 2011Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure.
BACKGROUND
Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure.
OBJECTIVE
To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens.
METHODS
According to a retrospective cohort design, we followed 2 groups of patients with CHF - whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril), and with left ventricular ejection fraction (LVEF) < 50%, by distinguishing them by ACE-inhibitor dosing: average-low (<10 mg per day) or "high" dose (>10 mg per day) of enalapril or lisinopril. Worsened renal failure (ARD) was defined by Cr increase >30% from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables: ACE-inhibitors "high" dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur), diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg.
RESULTS
57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8%) patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050) and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157) were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes.
CONCLUSION
In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.
Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Creatinine; Diabetes Mellitus; Diuretics; Drug Therapy, Combination; Enalapril; Epidemiologic Methods; Female; Heart Failure; Humans; Lisinopril; Male; Reference Values; Renal Insufficiency; Risk Factors
PubMed: 22001954
DOI: 10.1590/s0066-782x2011005000100 -
Journal of the... Mar 2003Several clinical trials have consistently shown that antihypertensive treatment, particularly with angiotensin-converting enzyme inhibitors (ACE-I) reduces albuminuria... (Review)
Review
Several clinical trials have consistently shown that antihypertensive treatment, particularly with angiotensin-converting enzyme inhibitors (ACE-I) reduces albuminuria in Type 1 diabetic patients. More recently, data on the beneficial effects of ACE-I on the preservation of glomerular filtration rate and renal ultrastructure have emerged. However, in general, these trials have recruited a wide spectrum of diabetics, including some patients with severe albuminuria. Thus, the question of the ideal stage at which to instigate what is likely to be lifelong therapy in young people still remains unanswered. Exercise is known to significantly increase both blood pressure (BP) and urinary albumin excretion (UAE), both of which are important determinants of progression of nephropathy in diabetes. Thus, it is possible that exercise may have an adverse effect on diabetic renal disease. The effects of ACE-I on exercise-BP and exercise-UAE in microalbuminuric Type 1 diabetic patients has not been examined in long-term placebo-controlled studies. In the second part of this two-part review, we examine the effects of the ACE-I, lisinopril, 20 mg o.d. for two years, in comparison with placebo, on UAE, 24-hour ambulatory BP, exercise-BP, exercise-UAE and renal haemodynamics in 22 patients with Type 1 diabetes and low-grade microalbuminuria. We further discuss the effects of ACE-I on nephropathy and other complications of diabetes.
Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Humans
PubMed: 12692749
DOI: 10.3317/jraas.2003.002 -
The Korean Journal of Internal Medicine Mar 2021Inhibitors of the renin-angiotensin system, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), reportedly have anti-inflammatory... (Observational Study)
Observational Study
BACKGROUND/AIMS
Inhibitors of the renin-angiotensin system, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), reportedly have anti-inflammatory effects. This study assessed the association of prior use of ACE inhibitors and ARBs with sepsis-related clinical outcomes.
METHODS
A population-based observational study was conducted using the Health Insurance Review and Assessment Service claims data. Among the adult patients hospitalized with new onset of sepsis in 2012, patients who took ARBs or ACE inhibitors at least 30 days prior to hospitalization were analyzed. Generalized linear models and logistic regression were used to examine the relation between the prior use of medication and clinical outcomes, such as in-hospital mortality, mechanical ventilation, and length of stay.
RESULTS
Of a total of 27,628 patients who were hospitalized for sepsis, the ACE inhibitor, ARB, and non-user groups included 1,214 (4.4%), 3,951 (14.4%), and 22,463 (82.1%) patients, respectively. As the patients in the ACE inhibitor and ARB groups had several comorbid conditions, higher rates of intensive care unit admission, hemodialysis, and mechanical ventilation were observed. However, after covariate adjustment, the use of ACE inhibitor (odds ratio [OR], 0.752; 95% confidence interval [CI], 0.661 to 0.855) or ARB (OR, 0.575; 95% CI, 0.532 to 0.621) was significantly associated with a lower rate of in-hospital mortality.
CONCLUSION
Pre-hospitalization use of ACE inhibitors or ARBs for sepsis was an independent factor for a lower rate of in-hospital mortality.
Topics: Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Hospital Mortality; Humans; Renin-Angiotensin System; Sepsis
PubMed: 32264653
DOI: 10.3904/kjim.2019.262