Converting Enzyme Inhibitors In Patients Research Articles

Effectiveness of sacubitril-varsartan versus angiotensin converting enzyme inhibitors in patients hospitalized for acute heart failure: a retrospective cohort study of the RICA registry.

Sacubitril-valsartan has been shown to reduce hospitalizations and mortality in patients with heart failure (HF) and reduced ejection fraction. The PIONEER-HF trial demonstrated that initiation of the drug during acute HF hospitalization reduced NT-proBNP levels and a post-hoc analysis of the trial found a reduction in HF hospitalizations and deaths. Real-life studies in the elderly population are scarce. The aim of our study was to assess the effectiveness of sacubitril-valsartan versus angiotensin converting enzyme inhibitors (ACEI) in elderly patients who initiate this treatment during hospitalization for acute HF. We conducted a retrospective cohort study using the Spanish acute heart failure registry (RICA) comparing rehospitalizations and deaths at 3 months and 1 year among patients aged 70 years or older who had initiated treatment with sacubitril-valsartan during hospitalization for acute HF versus those treated with ACEI. One hundred and ninety-nine patients hospitalized between October 2016 and November 2020 were included, with a median age of 82 years and high rate of comorbidity. Of these, 107 were treated with sacubitril-valsartan and 92 with ACEI. The adjusted OR for readmission for HF at 3 months was 0.906 (95% CI: 0.241-3.404) and for the combined variable readmission for HF or death at 3 months was 0.696 (95% CI: 0.224-2.167). The adjusted OR for HF readmission at one year was 0.696 (95% CI: 0.224 -2.167). and for the combined variable HF readmission or death at one year 0.724 (95% CI: 0.325-1.612). Treatment with sacubitril-valsartan initiated early in hospitalization for HF in elderly patients with high comorbidity was associated with a trend towards a reduction in readmissions and death due to HF compared to treatment with ACEI, which did not reach statistical significance either at 3 months or 1 year of follow-up.

Use of angiotensin converting enzyme inhibitors in patients receiving therapeutic plasma exchange with a centrifuge-based apheresis system.

Angiotensin-converting enzyme inhibitors (ACEi) are frequently used antihypertensive medications with additional advantages such as reducing proteinuria and cardiovascular events. ACEi are commonly held at least 24 hours before a therapeutic plasma exchange (TPE) to reduce possibility of adverse events (AEs) including adverse drug reactions (ADR). The objective of this study was to determine if ACEi use increases the risk of ADR in patients receiving TPE with a conventional centrifuge-based apheresis system. This is a retrospective chart review study (n=252; 52% male). Binary logistic regression was used to analyze the association of ACEi use and AEs. Of 171 patients who had AE during TPE, only 38 patients were taking ACEi. There was no significant association between ACEi use and AEs after adjustments (odds ratio=0.885, 95% confidence interval: 0.468, 1.674). Our results suggest that risk of AEs is not higher in patients taking ACEi receiving TPE using a centrifuge-based machine. Randomized controlled prospective trials may be needed to further investigate this matter.

The effect of angiotensin converting enzyme inhibition on effective renal plasma flow in patients with diffuse renal parenchymal diseases and hypertension

Angiotensin converting enzyme inhibitors are commonly used to treat various hypertensive conditions and in addition to lowering blood pressure these drugs affect the local renal hemodynamic status, thereby influencing the glomerular filtration rate and effective renal plasma flow. The study was aimed at determining whether angiotensin converting enzyme inhibitors can produce significant changes in effective renal plasma flow in patients with parenchymal renal disease and to assess whether the changes depend on the pre-existing functional status of the kidney. The study included 80 subjects, 40 subjects with hypertension associated with diffuse renal parenchymal disease and 40 subjects with essential hypertension. All study subjects underwent the baseline effective renal plasma flow measurement and the repeated effective renal plasma flow measurement after administration of captopril. Effective renal plasma flow was determined by 131 I-hippuran clearance in blood samples taken at 20 and 30 minutes. Angiotensin converting enzyme inhibitors caused significant effective renal plasma flow changes in 55% of subjects with diffuse renal parenchymal disease and in 75% of subjects with essential hypertension. The effective renal plasma flow changes were more significant in subjects with preserved renal function (normal baseline effective renal plasma flow) compared to subjects with reduced baseline effective renal plasma flow. The application of angiotensin converting enzyme inhibitors in patients with diffuse renal parenchymal disease and in individuals with essential hypertension may result in significant hemodynamic changes in the kidney, accompanied by changes in effective renal plasma flow. The extent of the changes caused by angiotensin converting enzyme inhibitors depends on the preexisting functional status of the kidney.

Control of Coronary Heart Disease Risk Factors and Evidence-Based Therapies: Joint Efforts for Coronary Heart Disease Prevention in Spain

Secondary prevention in coronary heart disease is the prevention of occurrence of recurrent coronary events after clinical diagnosis. High level of adherence to secondary prevention interventions, especially aggressive lifestyle changes and pharmacotherapy can lead to significant decline in recurrent coronary events. Both international and Indian studies have reported low adherence to such therapies. Evidence-based useful interventions include regular physical activity, yoga, intake of healthy diet, smoking and tobacco use cessation and weight management. Pharmacotherapeutic interventions useful are anti-platelet therapy, target oriented lipid lowering therapy with statins, beta blockers and angiotensin converting enzyme inhibitors in patients with impaired left ventricular function. Hypertension and diabetes management with control to targets is important. Novel strategies include use of anticoagulants, anti-inflammatory drugs, and triglyceride lowering for residual risk. Physician and patient level interventions using multifaceted educational, socioeconomic and technological innovations are important to promote life-long adherence to these strategies.

Evidence for a dose effect of renin-angiotensin system inhibition on progression of microalbuminuria in Type 2 diabetes: a meta-analysis

Renin-angiotensin inhibitors in Type 2 diabetes and microalbuminuria reduce renal and cardiovascular risk, but evidence supporting use of maximal tolerated dose is unclear. We aimed to determine the extent of renin-angiotensin inhibitor dose-dependent effects from randomized trials carried out in a clinical setting. In a meta-analysis of randomized clinical trials, alternate doses of angiotensin receptor blockers or angiotensin converting enzyme inhibitors in patients with Type 2 diabetes and microalbuminuria were compared. MEDLINE, EMBASE and the Cochrane Register of Controlled Trials were searched from January 2006 to August 2010. Trials prior to January 2006 were identified from a prior systematic review. Identified outcomes were albumin excretion rate, progression and regression of albuminuria and adverse events. Four trials including 1051 patients compared doses of angiotensin receptor blockers. No trials compared doses of angiotensin converting enzyme inhibitor. The percentage decline in albumin excretion rate from baseline was greater with higher doses (18% higher, 95% CI 8-28%), the regression to normoalbuminuria was greater (OR 1.66, 95% CI 1.22-2.27), with less progression to macroalbuminuria (OR 0.62, CI 0.38-1.02). Adverse events were fewer with lower-dose angiotensin receptor blockers (OR 1.32, 95% CI 0.90-1.92). Higher-dose compared with lower-dose angiotensin receptor blockers in Type 2 diabetes with microalbuminuria are associated with significantly reduced albumin excretion rate and increased regression to normoalbuminuria. Adverse events are more frequent, but not significantly so. There is potential for trials to determine clinical cardiovascular and renal outcomes at differing doses. Our findings support current recommendations to titrate renin-angiotensin inhibitors to maximum dose whilst considering risk of adverse side effects with higher doses.

Direct renin inhibition in addition to or as an alternative to angiotensin converting enzyme inhibition in patients with chronic systolic heart failure: rationale and design of the Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE) study

The renin-angiotensin-aldosterone system (RAAS) represents a key therapeutic target in heart failure (HF) management. However, conventional agents that block this system induce a reflex increase in plasma renin activity (PRA), which may lead to RAAS 'escape'. Direct renin inhibitors (DRIs) have been developed that decrease PRA and thus may provide a greater RAAS blockade. Aliskiren is the first orally active DRI. Plasma levels of B-type natriuretic peptide (BNP) have been observed to be reduced with aliskiren compared with placebo. The aim of the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failuRE (ATMOSPHERE) study is to evaluate the effect of both aliskiren and enalapril monotherapy and aliskiren/enalapril combination therapy on cardiovascular death and HF hospitalization in patients with chronic systolic HF, NYHA functional class II-IV symptoms, and elevated plasma levels of BNP. Methods Patients tolerant to at least 10 mg or equivalent of enalapril will undergo an open-label run-in period where they receive enalapril then aliskiren. Approximately 7000 patients tolerating this run-in period will then be randomized 1:1:1 to aliskiren monotherapy, enalapril monotherapy, or the combination. The primary endpoints of ATMOSPHERE are (i) whether the aliskiren/enalapril combination is superior to enalapril monotherapy in delaying time to first occurrence of cardiovascular death or HF hospitalization and (ii) whether aliskiren monotherapy is superior or at least non-inferior to enalapril monotherapy on this endpoint. Perspective The ATMOSPHERE study will definitively determine the role of a DRI strategy additional to or as an alternative to conventional RAAS blockade in patients with chronic systolic HF.

Response to Can the Study of Female Rats Help Our Understanding of Women?

We thank Campbell1 and agree with the opinions expressed in his letter. Observations made in animal models may not always accurately reflect responses in humans. What is clear, from our research and others, is that the responses to angiotensin II in female animal models and women are not identical to those in males, and the reasons for this are not well understood.2,3 Our recent observations suggest that there are sex differences in the regulation of arterial pressure in rats with an enhanced dilator arm of the renin-angiotensin system (RAS) in sexually mature females. Furthermore, our findings add to the evidence that the angiotensin type 2 receptor is a potential …

Sex differences in the effectiveness of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in patients with congestive heart failure

Sex differences in the effectiveness of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in patients with congestive heart failure

Sex differences in the effectiveness of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in patients with congestive heart failure — A population study

Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have been shown to improve survival in patients with congestive heart failure (CHF). We wish to determine whether there are sex-related differences in the optimal treatment of congestive heart failure. Using administrative databases, all patients >>=65 years of age discharged with a diagnosis of CHF between January 1998 and March 2003 and who filled a prescription for an ARB or an ACE inhibitor within 90 days of discharge were identified. Time to all-cause death in women and men on ACE inhibitors or ARBs was compared. There were 10,223 women (8627 ACE inhibitors and 1596 ARBs) and 9475 men (8484 ACE inhibitors and 991 ARBs). Hypertension was more common in women (50.1%) than men (33.1%). Women on ARBs had better survival than those on ACE inhibitors (adjusted hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.59, 0.80). There was no difference in survival in men prescribed ARBs compared to ACE inhibitors (HR 1.10, 95% CI 0.95, 1.30). These sex differences in treatment-related outcome are important but should be confirmed in a randomized trial before ARBs are preferentially prescribed to women with CHF.

821-1 Should beta-blockers be used before angiotensin converting enzyme inhibitors in patients with chronic heart failure? Meta-analysis of the prognostic benefit conferred by beta-blockers in patients not receiving ACE inhibitors

821-1 Should beta-blockers be used before angiotensin converting enzyme inhibitors in patients with chronic heart failure? Meta-analysis of the prognostic benefit conferred by beta-blockers in patients not receiving ACE inhibitors

Angiotensin II subtype 1-receptor antagonists in the treatment of diabetic nephropathy.

Diabetic nephropathy has become the leading cause of terminal renal failure in all Western nations due to a steady increase of patients with the renal complication of type 2 (non-insulin-dependent) diabetes mellitus. A number of modifiable risk factors have been identified that predispose to and/or accelerate renal disease in patients with diabetes mellitus. Among these, the level of blood pressure, even in the range of normotension according to World Health Organization or Joint National Committee definition, is closely related to the rate of progression of diabetic nephropathy. This has been documented in patients with incipient (microalbuminuric) and in patients with manifest (proteinuric) diabetic renal disease. Consequently, the treatment of even normotensive diabetics has been recommended once microalbuminuria is present, and blood pressure values in the low normal range should be aimed for. The selection of antihypertensive agents is also important, however, since a 'renoprotective effect' has been documented for drugs that interfere with the renin-angiotensin-aldosterone system such as angiotensin converting enzyme inhibitors. Recently, a new class of drugs that selectively inhibits this system by specifically targeting the angiotensin II receptor has been developed. These angiotensin II subtype 1-receptor antagonists are efficacious antihypertensive agents with a side-effect profile similar to placebo. Evidence for a renoprotective effect in patients with diabetic nephropathy from a large controlled clinical trial is still awaited, but data generated in animal experiments and in smaller clinical trials are encouraging. Currently, these drugs are a valuable substitute for angiotensin converting enzyme inhibitors in patients who experience side effects such as intractable cough.

Prognostic value of low versus high dosage of angiotensin converting enzyme inhibitors in patients awaiting heart transplantation: R. Berger, G. Kuchling, B. Frey, M. Grimm, G. Laufer, R. Pacher, B. Stanek. University of Vienna, Austria

Prognostic value of low versus high dosage of angiotensin converting enzyme inhibitors in patients awaiting heart transplantation: R. Berger, G. Kuchling, B. Frey, M. Grimm, G. Laufer, R. Pacher, B. Stanek. University of Vienna, Austria

Is preventive medicine responsible for the increasing prevalence of heart failure?

infarction. Risk factor~, responsible for the development and progression of atherosclerotic coronary artery disease are well known. The factors that predispose patients with coronary disease to the development of heart failure are not clear, but recurrent infarction is a major factor. Hoffman and colleagues 3 studied all patients with documented coronary artery disease eligible for the multicentre, randomised, controlled Coronary Artery Surgery Study to find out which modifiable cardiovascular risk factors predispose to heart failure. At the 12-year follow-up, the cumulative incidence of heart failure was 20.6%. Cigarette smoking, high body-mass index, myocardial infarction during follow-up, older age, female sex, and baseline left-ventricle dysfunction were risk factors for the development of heart failure. Other factors have also been implicated such as: myocardial wall stress, uncorrected myocardial ischaemia, persistent coronary artery occlusion, and neurohormonal (particularly renin-angiotensin and sympathetic) overactivity. The Framingham study ~ also identified the following independent risk factors for the development of heart failure: low vital capacity, rapid heart rate, diabetes, cardiac enlargement, high body-mass index (in women), high serum cholesterol (in men aged <65 years), cigarette smoking, proteinuria, and high haematocrit. These risk factors were in addition to hypertension, evidence of leftventricle hypertrophy on electrocardiogram (ECG), and coronary disease. The findings of this study would suggest that conventional strategies for secondary prevention of coronary artery disease may work as primary preventive measures of heart failure. There is evidence showing this effect in a number of settings.

Acute antiiscemic effect of angiotensin converting enzyme inhibition in patients with coronary artery disease

Acute antiiscemic effect of angiotensin converting enzyme inhibition in patients with coronary artery disease

Value of angiotensin converting enzyme inhibition in patients with myocardial infarction, aggressively treated with thrombolysis or acute PTCA

Value of angiotensin converting enzyme inhibition in patients with myocardial infarction, aggressively treated with thrombolysis or acute PTCA

Influence of angiotensin II on circulating adhesion molecules and blood leukocyte count in vivo

The mechanism of the beneficial effect of angiotensin converting enzyme inhibitors in patients with myocardial infarction is not clear. Recent in vitro data indicate that angiotensin II (AII) stimulates the expression of adhesion molecules and thus activates leukocyte endothelial interactions. In eight healthy volunteers we investigated the influence of exogenous AII on circulating adhesion molecules and on the blood leukocyte count. A systemically effective and a systemically ineffective dose of AII were administered intravenously over 4 h in a single blind crossover design. Examination of the time course of circulating intercellular and vascular adhesion molecules and E-selectin (cICAM-1, cVCAM-1, cE-selectin-1) in response to the AII infusion revealed increases of up to 11% (especially in cVCAM-1 levels) at single time points, but no significant sustained elevation or trend that can be interpreted as a drug-induced effect. The systemically effective dose, which induced an increase in mean arterial blood pressure from 80 to 108 mmHg (1 mmHg = 133.3 Pa), resulted in a significant increase in blood leukocytes, from 4.8 +/- 0.3 to 5.5 +/- 0.3 g/L (p < 0.05); the systemically ineffective AII dose did not alter blood leukocyte count significantly. Although we did not find an influence of AII on circulating adhesion molecules in vivo, we observed an increase in the blood leukocyte count; thus it may be intriguing to assess whether renin-angiotensin system modulating drugs might exert their favorable effect in ischemic diseases at least in part via an influence on leukocytes.

Enalapril saved more lives at minimal extra cost in congestive heart failure

Source Citation Paul SD, Kuntz KM, Eagle KA, Weinstein MC. Costs and effectiveness of angiotensin converting enzyme inhibition in patients with congestive heart failure. Arch Intern Med. 1994 May 2...

Hemodynamic and morphologic changes after long-term angiotensin converting enzyme inhibition in patients with chronic valvular regurgitation

Angiotensin converting enzyme (ACE) inhibitors decrease preload and afterload and are therefore of potential value in valvular regurgitation. The present study was designed to assess the effects of treatment for 1 year with an ACE inhibitor on myocardial performance. Twenty-four patients with isolated moderate to severe chronic aortic regurgitation or mitral regurgitation who were free of coronary disease were studied before treatment (control) with the ACE inhibitor quinapril and were then followed for 1 year during quinapril therapy (10-20 mg/day). After 1 year of ACE inhibition, the regurgitant fraction fell by 27 and 42%, compared with control values, in the aortic and mitral regurgitation groups, respectively (P = 0.0001). The left ventricular end-diastolic volume was reduced from 150 +/- 33 to 128 +/- 30 ml/m2 in the aortic regurgitation group, and from 146 +/- 26 to 109 +/- 24 ml/m2 in the mitral regurgitation group (P = 0.0001 for each). End-systolic volume decreased from 55 +/- 27 to 44 +/- 28 ml/m2 in the aortic regurgitation group (P = 0.005) and from 63 +/- 43 to 47 +/- 29 ml/m2 in the mitral regurgitation group (P = 0.002). The left ventricular ejection fraction increased slightly at rest and during exercise in patients with aortic regurgitation, but showed no change in the mitral regurgitation patients after 1 year of quinapril treatment. Echocardiographic studies showed that after 1 year of therapy there was a decrease of about 10% in the left ventricular end-diastolic and end-systolic diameter in both patient groups. Moreover, the left ventricular mass was reduced by 35% in the aortic regurgitation group (P = 0.0001), and left ventricular hypertrophy, which was present in all patients, was reversed completely. In the mitral regurgitation group, a mass reduction of 15% was observed after 1 year of quinapril treatment, and the septal wall thickness, which indicated borderline hypertrophy, decreased to normal. These results demonstrate that long-term ACE inhibition in patients with valvular regurgitation reverses left ventricular dilation and reduces left ventricular mass and hypertrophy, thereby improving left ventricular function. Further, they suggest that ACE inhibition may have the potential to delay aortic or mitral valve replacement.

Costs and effectiveness of angiotensin converting enzyme inhibition in patients with congestive heart failure

Costs and effectiveness of angiotensin converting enzyme inhibition in patients with congestive heart failure

Efficacy of phosphodiesterase inhibition with milrinone in combination with converting enzyme inhibitors in patients with heart failure

We describe the results of two placebo-controlled trials (MIL-1077 and MIL-1078) designed to evaluate the clinical efficacy of oral milrinone administered together with converting enzyme inhibitors to patients with congestive heart failure. Although these trials were terminated prematurely, they provide the only controlled data regarding the effect of oral milrinone on exercise capacity in patients receiving converting enzyme inhibitors. Of the 254 patients randomized, 140 completed one of the trials or reached an end point and are the basis of this report. In both trials, there was a clear trend for an increase in exercise capacity in the milrinone-treated patients (+ 26 ± 8% vs. +5 ± 7% in MIL-1077 and + 11 ± 5% vs. + 2 ± 4% in MIL-1078). Symptoms of congestive heart failure were decreased in one trial but not the other. Quality of life, as assessed by a questionnaire, was not effected in either trial. There was an increased incidence of adverse events in milrinone-treated patients. Adverse events related primarily to hypotension and vasodilation led to discontinuation of drug in 18 milrinone-treated patients vs. 1 placebo-treated patient. Milrinone had little or no proarrhythmic effect and cardiovascular deaths were distributed equally between the milrinone and placebo groups. These data suggest that when used in combination with a converting enzyme inhibitor, oral milrinone improves exercise capacity but is associated with a high incidence of adverse events that appear to be related to excessive vasodilation.