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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over 100 years of scientific investigation has established that angiotensin-converting enzyme (ACE) plays an important role in both the renin-angiotensin system and the kinin-kallekrein system. ACE inhibitors--which stem the production of angiotensin II, a potent vasoconstrictor--have proved to be useful agents in the management of hypertension, in the prevention and treatment of heart failure, and in the improvement of endothelial function. Generally, ACE inhibitors are as efficacious as beta blockers and thiazide diuretics in reducing blood pressure and also induce regression of left ventricular hypertrophy. Many trials-including the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS), the Veteran's Administration Cooperative Vasodilator-Heart Failure Trial (V-HeFT I), the Studies of Left Ventricular Dysfunction (SOLVD), and the Survival and Ventricular Enlargement (SAVE) trial--have demonstrated the ability of ACE inhibitors to reduce mortality within a wide range of heart failure, from asymptomatic left ventricular dysfunction to severe heart failure. The SAVE trial specifically evaluated the effects on post-myocardial infarction mortality and remodeling and found that ACE inhibitors were effective in reducing both. Further studies are assessing the potential additional antiatherosclerotic aspects of ACE inhibitors. Initial research indicates a reversal of endothelial dysfunction in atherosclerotic animals, and subsequent clinical trials, including the Trial on Reversing ENdothelial Dysfunction (TREND), support the likelihood of a similar effect in humans. Beneficial effects in hypertension or heart failure may also be gained with other interruptors of the renin-angiotensin system, such as angiotensin receptor blockers. Results from studies assessing these receptor blockers will bring greater understanding to the mechanism of action of ACE inhibitors.
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PMID:Evolution of angiotensin-converting enzyme inhibition in hypertension, heart failure, and vascular protection. 970 65

This study examined the effect of enalapril on survival, resource use, and cost of care in patients with left ventricular dysfunction and hypertension using a retrospective analysis of patients who participated in the Studies of Left Ventricular Dysfunction (SOLVD). Among the 6797 SOLVD participants, 1917 patients had either elevated systolic (> or = 140 mm Hg) or diastolic (> or = 90 mm Hg) blood pressure. Therapy with enalapril was associated with a significant relative risk reduction for mortality (RR = 0.819, 95% CI: 0.68 to 0.98; P = .03). This resulted in a gain of 0.11 years (95% CI: 0.00 to 0.20 years) of survival during the average 2.8 year follow-up for this subgroup and was projected to result in a gain of 2.14 years (95% CI: 0.05 to 4.21 years) during the patient's lifetime. Enalapril significantly reduced the risk of first hospitalization for heart failure by 37%. For all types of hospitalizations, there was an average reduction of 32 hospitalizations per 100 patients treated with enalapril during the trial period (95% CI: 11.8 to 52.2 hospitalizations avoided per 100 patients), resulting in an estimated net savings of $1656 per patient during the trial period (95% CI: increased cost of $191 to savings of $3502). Although the projected lifetime net savings of $1456 was not significant (95% CI: increased cost of $9243 to saving of $12,527), evaluation of the cost per life year saved indicated that enalapril represented a cost-effective strategy. The estimated clinical benefit of enalapril among the hypertensive subgroup in SOLVD supports the recommendation that angiotensin converting enzyme (ACE) inhibitors should be considered as first line pharmacologic therapy for hypertensive patients with left ventricular dysfunction. From both the clinical and economic viewpoints, ACE inhibitors provide important clinical benefits and are cost-effective.
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PMID:The cost and cardioprotective effects of enalapril in hypertensive patients with left ventricular dysfunction. 988 Jan 25

Enalapril is an angiotensin converting enzyme (ACE) inhibitor with an established clinical profile. In patients with symptomatic heart failure, enalapril reduces overall mortality, death from progressive heart failure and hospitalisation rates. In those with asymptomatic left ventricular dysfunction, enalapril decreases the combined risk of death and development of heart failure, and the risk of death and hospitalisation. The effects of enalapril in reducing hospitalisation rates in symptomatic patients translate into net savings in healthcare costs in heart failure. Enalapril also produces modest benefits in quality-of-life (QOL) parameters in patients with symptomatic heart failure as shown in well controlled studies. Its effects appear similar to those of hydralazine plus isosorbide dinitrate. The influence of enalapril on quality of life in patients with asymptomatic disease is minimal but not deleterious. Enalapril generally either maintains or slightly improves quality of life from baseline in patients with mild to moderate hypertension. The drug appears to have a QOL profile that is more favourable than that of propranolol and similar to those of most other comparator drugs, as assessed by subjective measures of quality of life. Clarification is required of its QOL profile relative to that of captopril, in view of conflicting results in the literature. The effects of enalapril on cognitive and psychomotor function appear to resemble those of comparator agents. Thus, enalapril has modest beneficial effects on the quality of life of patients with symptomatic heart failure, while generally maintaining quality of life in patients with asymptomatic left ventricular dysfunction or mild to moderate hypertension. Enalapril is a cost-effective treatment in heart failure that would be expected to yield considerable cost savings in this therapeutic area.
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PMID:Enalapril: a review of quality-of-life and pharmacoeconomic aspects of its use in heart failure and mild to moderate hypertension. 1014 41

Chronic severe subclinical systemic hypertension was diagnosed in a 28-yr-old male western lowland gorilla (Gorilla gorilla gorilla). Thoracic radiography, electrocardiography, and echocardiography revealed an enlarged heart with a hypertrophied left ventricle, mitral regurgitation, and a persistent left bundle branch block. Enalapril, later combined with nifedipine, was of some value in reducing the hypertension, with partial reversal of cardiac enlargement and resolution of the bundle branch block. Two years after initiation of treatment, the gorilla developed lethargy and dyspnea. The diagnosis of heart failure was confirmed under anesthesia; the gorilla did not recover and was euthanized. Postmortem examination confirmed congestive heart failure with chronic, fibrosing cardiomyopathy similar to that in other gorillas.
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PMID:Chronic hypertension with subsequent congestive heart failure in a western lowland gorilla (Gorilla gorilla gorilla). 1048 43

The aim of the study was to investigate the effect of angiotensin-converting enzyme inhibitor enalapril and non-peptide blocker of AT1 receptors losartan on endothelial function of the shoulder artery in patients with congestive cardiac insufficiency. The examination covered 96 patients (mean age 46.71 +/- 4.13) with stable effort angina (functional class II-III) and circulatory insufficiency (NYHA functional class II-III) having end-diastolic left-ventricular volume > 160 ml, left ventricular ejection fraction < 35%, sinus rhythm, cardiothoracal index > 0.55 units. Patients with fibrillar tachyarrhythmia, high grade blocks, pacemaker migration, artificial pacemaker, myocardial infarction were not included in the trial. The patients were randomized into 3 groups 32 patients each. In addition to basic therapy patients of group 1 received long-acting nitrates, digoxin, aspirin and furosemide; group 2--enalapril in daily dose 10 mg; group 3--losartan in daily dose 25 mg. A course of treatment lasted 12 weeks. Endothelial function was assessed by high resolution echography, dopplerography performed before and after temporary occlusion of the shoulder artery and sublingual nitroglycerin. In patients with cardiac insufficiency, accelerated blood flow in the shoulder artery after its temporary occlusion promoted realization of the vasoconstrictory reaction. This was verified as endothelial dysfunction. In the course of the treatment all the patients achieved insignificant increase of the shoulder artery initial diameter. After sublingual intake of nitroglycerin vasodilation was also insignificant. 12-week enalapril and losartan prevented vasoconstriction in the shoulder artery in response to quicker circulation following arterial occlusion. However, higher maximal flow speed did not correspond to the increment in the artery diameter after the occlusion in any group. The flow-induced vasodilation was more pronounced in the enalapril group. Losartan group had a trend to an increase in the inner diameter of the shoulder artery. It is shown that enalapril and losartan in congestive cardiac insufficiency improves endothelium-dependent vasodilation caused by nitroglycerin. Enalapril demonstrated stronger ability than losartan to reverse endothelial dysfunction in patients with cardiac insufficiency resultant from ischemic heart disease.
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PMID:[Prospects of endothelial dysfunction reversion in patients with congestive heart failure]. 1097 40

The aim of this study was to evaluate the acute effects of E-3174, a human active metabolite of the AT1 receptor antagonist, losartan, on hemodynamic functions in dogs with severe heart failure (HF). In dogs, insignificant plasma levels of E-3174 are present following administration of losartan, and therefore, the effects of these two drugs can be studied independently in the dog. HF was established by rapid pacing of the right ventricle (250-270 beats/min) for 4 weeks. We examined changes in cardiovascular functions after acute intravenous administration of losartan (1 mg/kg) and E-3174 (0.3 and 1 mg/kg), as well as an ACE inhibitor, enalapril (0.3 and 1 mg/kg), under condition of HF. The HF before treatment was characterized by increases in pre- and after-load of the left ventricle (LV), consequent low cardiac output, and LV dilatation. E-3174 at 0.3 and 1 mg/kg reduced pulmonary artery pressure (-13+/-6% and -22+/-3% from baseline, respectively, p<0.05), pulmonary capillary wedge pressure (-18+/-4% and -36+/-10%, p<0.05) and mean arterial pressure (-24+/-2% and -36+/-7%, p<0.05), increased stroke volume (SV: +12+/-7% p>0.05; +36 +/-19%, p<0.05), and reduced peripheral resistance (-23+/-5% and -41+/-9%, p<0.05), but had no effect on the first derivative of left ventricular pressure (dP/dt/P) or the time constant for relaxation. Effects of losartan at 1 mg/kg were similar to those of 0.3 mg/kg of E-3174. Enalapril at 1 mg/kg caused changes comparable to those seen after E-3174 administration (1 mg/kg), except that the increase in SV (+16+/-8%, p<0.05) with enalapril was not as great as that with E-3174. Both losartan at 1 mg/kg and E-3174 at 0.3 and 1 mg/kg increased fractional shortening to a similar extent (FS: +52+/-12%, +47+/-8% and +56+/-8%), while enalapril at 0.3 and 1 mg/kg had no significant effects on FS. Reflex elevation of plasma renin activity induced by 1 mg/kg of E-3174 was similar to that caused by 1 mg/kg of enalapril, suggesting that the two drugs achieved similar inhibition of the endogenous renin angiotensin system. Our study demonstrated that acute blockade of the AT1 receptor with E-3174 reduced elevated pre- and after-load and consequently increased stroke volume in a canine HF model. With the exception of changes in stroke volume, these effects of E-3174 were comparable to those produced by enalapril, and were 3 times stronger than those by losartan.
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PMID:Acute effects of E-3174, a human active metabolite of losartan, on the cardiovascular system in tachycardia-induced canine heart failure. 1121 32

We evaluated the effects of chronic oral administration of an angiotensin II type 1 (AT1)-receptor antagonist YM358 and an angiotensin converting enzyme inhibitor enalapril on hemodynamics and cardiac hypertrophy in rats with volume overload-induced heart failure. We assessed changes of cardiac hemodynamics and cardiac hypertrophy at 2 and 4 weeks after administration of YM358 (3, 30 mg/kg per day) or enalapril (30 mg/kg per day) in abdominal aortocaval shunt rats. YM358 (30 mg/kg) attenuated increases of left ventricle (LV)/body weight (BW), left atrium (LA)/BW, right ventricle (RV)/BW and heart/BW ratios, but did not affect cardiac hemodynamics in shunt rats. Enalapril also reduced the increased LV/BW and heart/BW ratios together with significant reductions of systolic blood pressure, left ventricular systolic pressure and the first derivative of left ventricular pressure. These data suggest that the effects on attenuation of the development of cardiac hypertrophy are not different for YM358 and enalapril, although the effects on cardiac hemodynamics are different for the same dosages. The attenuating action of YM358 on cardiac hypertrophy was independent of the action on hemodynamics and indicated the direct action of the AT1 receptor on the heart.
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PMID:Comparison of the angiotensin II type 1-receptor antagonist YM358 and the angiotensin-converting enzyme inhibitor enalapril in rats with cardiac volume overload. 1143 Apr 76

Proven cardiovascular benefit from angiotensin-converting enzyme (ACE) inhibition is a cornerstone of evidence-based medicine. The first study to show dramatic benefits from ACE inhibition was the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS-I), in which a 31% decrease in the rate of death was observed in patients with severe heart failure at the end of 1 year of enalapril treatment (p = 0.001). This result led to large long-term studies-including Survival and Ventricular Enlargement (SAVE), Acute Infarction Ramipril Efficacy (AIRE), Trandolapril Cardiac Evaluation (TRACE), and Study of Left Ventricular Dysfunction (SOLVD)-which verified that ACE inhibition decreases heart failure, myocardial infarction (MI), and mortality, and that striking benefit could be observed within 30 days. Short-term studies of patients in the acute phase of a heart attack verified that ACE inhibition provided rapid benefits. A meta-analysis of short-term (up to 8 weeks) studies of ACE inhibition (including CONSENSUS-II, Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico [GISSI]-3, International Study of Infarct Survival [ISIS]-4, and the Chinese Captopril Study [CCS]-1) demonstrated that post-MI risk was reduced by 10% within the first day of treatment. The immediacy of the benefit suggested that ACE inhibition not only improved cardiovascular function in failing hearts but also affected important mechanisms in patients without overt heart failure. Effects on more general mechanisms of heart disease suggested that patients with problems other than hypertension or heart failure might benefit from ACE inhibitors. The Heart Outcomes Prevention Evaluation (HOPE) study investigated the hypothesis that ACE inhibition would confer benefits to patients who were at high risk for cardiovascular events, but who were without left ventricular dysfunction or heart failure. Long-term reductions in MI, stroke, cardiac arrest, and heart failure, as well as improvements in mortality, were observed in this population after treatment with ACE inhibitors. Substudies of the HOPE study revealed that ACE inhibition reduced progression of atherosclerosis and improved myocardial remodeling. Taken together, these studies provide evidence that supports treatment of a broad population of patients at risk for cardiovascular events with ACE inhibitors. The next step is to combine ACE inhibition with other treatments to maximize patient benefit. The Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) will compare the efficacy of an ACE inhibitor (ramipril) with an angiotensin receptor blocker (telmisartan), and determine whether these treatments in combination will further reduce morbidity and mortality from cardiovascular disease.
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PMID:Angiotensin II and trials of cardiovascular outcomes. 1183 5

Bristol-Myers Squibb (BMS) is developing the vasopeptidase inihibitor, omapatrilat, a dual inhibitor of angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), for the potential treatment of cardiovascular diseases such as hypertension and heart failure [306287]. An NDA for the use of omapatrilat in hypertension was filed with the FDA and the regulatory authorities in the EU in December 1999 [351207], [353287]. In April 2000, BMS voluntarily withdrew the NDA in response to questions raised by the FDA regarding the comparative incidence and severity of an infrequent side effect (angioedema) reported within the NDA database. Prospective controlled clinical studies in patients with hypertension and heart failure were to continue. In May 2001, BMS reported that its blinded omapatrilat hypertension study was continuing and, pending supportive results from a data analysis anticipated in late summer/early autumn 2001, the company expected to refile an NDA with the FDA [409203]. In July 2000, BMS reported that it planned to conduct a multinational, 25,000 patient study (OCTAVE - Omapatrilat Cardiovascular Treatment Assessment Versus Enalapril) to compare the efficacy and safety of omapatrilat against enalapril in the treatment of hypertension [374909]. The OCTAVE trial was expected to generate data by mid-2001, which could allow for a launch by early 2002 [380280]. Phase III trials for hypertension had commenced by January 1998 [273646]. In January 2001, Merrill Lynch expected BMS to refile its NDA with the FDA in the second half of 2001 [395423]. In February 2001, Credit Suisse First Boston made a similar prediction, adding that it believed BMS would launch the drug in late 2002 or early 2003. The analysts also predicted peak sales for the drug of $585 million in 2005 [399484]. In May 2001, Merrill Lynch estimated sales of $1.8 billion in 2005 [411811].
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PMID:Omapatrilat. Bristol-Myers Squibb. 1189 Mar 57

Although heart failure in cats is treated with angiotensin converting enzyme (ACE) inhibitors, data on the effects of different doses of enalapril on hemodynamics and the inhibition of ACE activity have not been published. To evaluate the effect of enalapril, 0.25, 0.5, or 1.0 mg/kg was given once (s.i.d., p.o.) or twice (b.i.d., p.o.) a day, and plasma ACE activity, indirect blood pressure, and heart rate were measured. Plasma ACE activity and blood pressure fell dose-dependently. There was a biphasic effect on blood pressure with twice daily administration. Enalapril 0.25 mg/kg b.i.d. inhibited plasma ACE activity by 40% after 24 hr, which was almost the same as the effect of 0.5 and 1.0 mg/kg s.i.d., and 0.5 and 1.0 mg/kg b.i.d., while 0.25 mg/kg s.i.d. inhibited it by 23%. Thus, enalapril with a daily dose exceeding 0.5 mg/kg may provide similar efficacy of ACE inhibition in cats.
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PMID:Dose-dependent inhibition of angiotensin converting enzyme by enalapril in cats. 1201 88


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