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

Over the past 4 years, six angiotensin II receptor antagonists (ARBs) were approved for treating essential hypertension. They differ with respect to dosing, metabolism, elimination, clinical efficacy, and investigational applications. Candesartan cilexetil is the only prodrug among the agents. Losartan is distinguished from other ARBs by cytochrome P450 (CYP) 3A4- and CYP2C9-mediated biotransformation to its active metabolite EXP-3174. No ARB requires dosage adjustment for renal impairment, but the initial dose of losartan should be reduced 50% in hepatically impaired patients. None of the drugs is significantly cleared by hemodialysis. Completion of continuing trials will elucidate the drugs' role in treating heart failure, cerebral stroke, and myocardial infarction.
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PMID:Pharmacologic, pharmacokinetic, and therapeutic differences among angiotensin II receptor antagonists. 1067 91

Despite many recent advances, heart failure continues to be a major cause of morbidity and mortality in the United States. Once a patient is identified and evaluated as having heart failure, nonpharmacologic therapies such as a dietary restrictions, lifestyle changes, exercise strategies, and patient education are initiated as well as pharmacologic therapy. Angiotensin-converting-enzyme inhibitors, diuretics, and digoxin all are considered traditional therapy in the management of chronic heart failure associated with left ventricular systolic dysfunction. The role of newer therapies such as beta-blockers and angiotensin II receptor antagonists in the treatment of heart failure is in the process of being defined. Furthermore, new data is appearing concerning calcium channel blockers, spironolactone, and combinations of the various agents. Appropriate use of the traditional agents accompanied by a through understanding of the newer therapies and their roles is essential to the continued reduction of the morbidity and mortality associated with heart failure.
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PMID:Clinical and pharmacologic management of chronic heart failure associated with left ventricular systolic dysfunction. 1071 Nov 33

Angiotensin converting enzyme (ACE) inhibitors and diuretics represent the first line of therapy in patients with symptomatic heart failure. Inhibition of angiotensin II production is, however, incomplete with ACE inhibitors, due to non-ACE dependent conversion pathways. Moreover, some patients are intolerant to ACE inhibitors due to side effects or renal insufficiency. Angiotensin II receptor blockers may be an alternative to, or an additional treatment in heart failure. Preliminary studies comparing the angiotensin II receptor blocker losartan with placebo have demonstrated improved haemodynamic parameters, reduced hospitalisation and mortality in patients with heart failure. Reduced morbidity and mortality have also been found with losartan treatment, as compared to the ACE inhibitor captopril. This paper discusses the role of angiotensin II receptor blockers in the treatment of heart failure. Some results from published studies and a short description of ongoing trials are presented.
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PMID:[Use of angiotensin II receptor blockaders in heart failure]. 1080 6

The treatment of congestive heart failure focuses on three steps: 1. Elimination of the precipitating cause or mechanism, and/or treatment of the underlying disease respectively. 2. Treatment of the failing heart syndrome itself. We shall concern ourselves with pharmacotherapy, omitting technical and surgical aspects. 3. Prophylactic treatment of complications, such as thromboembolism and arrhythmias. Drugs for the treatment of heart failure can be classified as follows: 1. Diuretics 2. Vasodilators 3. Neurohumoral Inhibitors 4. Inotropic drugs. Diuretics improve symptoms and exercise capacity and probably survival. They are the drug of first choice in acute and chronic heart failure. Potassium supplementation is necessary. Renal function needs to be monitored. The aldosterone antagonist spironolactone has probably important effects upon the myocardium. It retards fibrous tissue development and improves prognosis. Vasodilators unload the heart and improve contractile geometry and hemodynamics, thereby lessening symptoms. Prognosis, however, is not affected. They are indispensable in acute heart failure. In longterm treatment only the combination of nitrates with hydralazin has been shown to be effective. Angiotensin converting enzyme inhibitors combine vasodilation with neurohumoral inhibition. They are most effective in improving symptoms, exercise capacity and surviving chronic heart failure. If side effects (cough, allergy) prevent their use, then angiotensin II receptor antagonists can be used with equal benefit. However, both groups of drugs impair renal function and cannot be given in advanced renal failure or renal artery stenosis. Beta-receptor antagonists, previously considered contraindicated in heart failure are today amongst the most important drugs in heart failure. They improve survival and retard the need for cardiac transplantation in advanced failure. Their use, however, is rather difficult requiring extremely slow dose titration beginning with very low doses. Inotropic drugs are today mainly used in acute failure and cardiogenic shock. In longterm treatment only the digitalisglycosides have been shown to be effective in improving symptoms, exercise capacity and the general clinical course. Often antiarrhythmic treatment is necessary. Here amiodarone is the drug of choice today if beta blockers do not suffice. Prophylactic anticoagulation is indicated in all cases NYHA III and IV, with large hearts already in II. Future developments may include new inotropes, the ANP-system, and cytokines, as well as gene therapy for correction of myocardial phenotype change.
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PMID:[Therapy for heart failure]. 1085 91

This study evaluated the effect of angiotensin II receptor blockade on cardiac autonomic control adaptation and urine output in response to acute isotonic volume load in patients with idiopathic dilated cardiomyopathy (DCM) and asymptomatic to mildly symptomatic heart failure. Left ventricular volumes and heart rate variability measurements were assessed at baseline and during intravenous saline load in 14 patients before and after 2 mo of losartan treatment. After losartan treatment, blood pressure values were lower, whereas left ventricular ejection fraction was higher (F = 79, P < 0.001), than before treatment. During saline load, ejection fraction decreased before losartan treatment (F = 5.6, P < 0.05) but did not change after treatment. Urinary volume, unchanged during saline load in untreated patients, increased after losartan (F = 9.38, P < 0. 001). Time-domain measurements that represent vagal modulation of heart rate (root-mean-square successive differences and percentage of differences between successive R-R intervals >50 ms) decreased during saline load in untreated patients (F = 3.1, P < 0.05 and F = 6.5, P < 0.01, respectively), but not after losartan. Similarly, a decrease in very low frequency (F = 3.2, P < 0.05), low-frequency (F = 2.9, P < 0.05), and high-frequency power (F = 6.1, P < 0.01) after saline load was observed only in untreated patients. In patients with DCM, losartan treatment improves the cardiac autonomic adaptation and increases urine output in response to volume overload.
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PMID:Effects of losartan treatment on cardiac autonomic control during volume loading in patients with DCM. 1089 44

The goals of antihypertensive therapy are to lower blood pressure and prevent end-organ damage without side effects, which affect quality of life. The antihypertensive drugs, regardless of class, all lower blood pressure, but they vary in their mechanisms of action, side-effect profiles, suitability for patients with other comorbid conditions, and ability to protect against the long-term sequelae of hypertension. The Sixth Report of the Joint National Committee on Prevention, Evaluation, and Treatment of High Blood Pressure (JNC-VI) recommends diuretics and beta-blockers as first-line therapy for uncomplicated hypertension, with diuretics also being strongly preferred for patients with isolated systolic hypertension or hypertension and heart failure and beta-blockers being strongly preferred for patients who have had a myocardial infarction (MI) and those with hypertension and angina, atrial tachycardia, or atrial fibrillation. Because angiotensin-converting enzyme (ACE) inhibitors have been shown to be cardioprotective and renoprotective in patients with diabetes or impaired left ventricular (LV) function, the JNC-VI recommends them as first-line therapy in patients with diabetes with proteinuria, heart failure, and MI complicated by LV dysfunction. It recommends calcium channel blockers for hypertensive patients with angina, long-acting dihydropyridines for those with isolated systolic hypertension, and the nondihydropyridines for those with atrial tachycardia or fibrillation, diabetes, and proteinuria. The angiotensin II receptor blockers (ARBs) share many of the organ-protective effects of ACE inhibitors when studied in animal models. They are effective in lowering blood pressure and have a very benign side-effect profile; however, these agents have not been available long enough to ascertain their efficacy in protecting against long-term complications.
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PMID:Clinical overview of antihypertensive classes--clinically relevant differences: myths or facts? Based on a presentation by Alan H. Gradman, MD. 1097 60

Inappropriate elevations in plasma aldosterone levels have multiple actions that play an important role in the pathophysiology of hypertension and heart failure. Patients with hypertensive cardiovascular disease are at increased risk for coronary artery disease, myocardial infarction, congestive heart failure, and sudden cardiac death. Despite long-term treatment with an angiotensin converting enzyme inhibitor or an angiotensin II receptor blocker, aldosterone levels usually remain high in these patients. The effectiveness of low-dose spironolactone raises the possibility that a nonselective aldosterone antagonist can block the deleterious effects of aldosterone on the cardiovascular system. However, side effects limit the use of this drug in many patients. The advent of selective aldosterone antagonists, which have a lower affinity for androgen and progesterone receptors, should minimize these side effects, leading to better compliance.
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PMID:The promise of selective aldosterone receptor antagonists for the treatment of hypertension and congestive heart failure. 1098 Nov 73

Two independent pharmacologic methods of specifically interfering with the renin-angiotensin-aldosterone system have been brought to the marketplace: angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). These agents have the potential not only to be very widely used for a broad variety of clinical indications but also to compete against each other as treatments for hypertension, heart failure, renal impairment, and other conditions. Many short-term comparative studies of these two classes of drugs have now been completed. Most have focused on surrogate endpoints, such as blood pressure, renal function, or cough. These studies have generally concluded that ARBs are better tolerated but that the two drug classes otherwise have similar efficacy. The largest clinical trial comparing ARBs and ACE inhibitors thus far completed, Evaluation of Losartan in the Elderly (ELITE 2), failed to confirm the results of a smaller study; it did not demonstrate a significant improvement in outcomes (death or hospitalization for heart failure) with an ARB used alone, despite better tolerability. Many longer-term outcome studies with survival endpoints are under way, but most will compare the combination against an ACE inhibitor alone. These studies will define the optimal use of these agents in medicine for decades to come.
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PMID:Therapeutic trials comparing angiotensin converting enzyme inhibitors and angiotensin II receptor blockers. 1098 Nov 76

These studies suggest that IGF-I and GH have generally favourable effects on the failing heart. They further demonstrate the ability of the severely depressed and failing heart to respond to the trophic and inotropic effects of GH. There is, however, a need for a better understanding of the mechanism of the contractility effect, the character of the hypertrophy observed (whether it is a more favourable type than that secondary to mechanical overload) and the vascular actions, both trophic and vasodilatory. In addition, the degree to which high-dose ACE inhibition or angiotensin II receptor blockade may inhibit some of these effects requires further study. Finally, it is clear that additional experimental studies and clinical trials are needed to investigate the long-term effects of GH on morbidity and mortality in heart failure, as well as the possible side-effects and other actions, such as the potential of GH to enhance skeletal muscle size and strength.
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PMID:Effects of growth hormone and insulin-like growth factor I in experimental heart failure. 1099 Jan 54

The diagnosis of diastolic heart failure (DHF) can be made when a patient has both symptoms and signs on physical exam of congestive heart failure (CHF), and normal left ventricular volume and ejection fraction. Documentation of abnormal diastolic function is confirmatory but not mandatory. Diastolic heart failure is a frequent cause of CHF (prevalence is 35% to 50%) and has a significant effect on mortality (5-year mortality rate is 25% to 35%) and morbidity (1-year readmission rate is 50%). Treatment should be targeted at symptoms, causal clinical disease, and underlying basic mechanisms. Symptom-targeted therapy: decrease pulmonary venous pressure using diuretics and long-acting nitrates, maintain atrial contraction and atrial ventricular synchrony, reduce heart rate using beta-adrenergic blockers and calcium channel blockers; increase exercise tolerance by reducing exercise- induced increases in blood pressure and heart rate using angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, and calcium channel blockers. Disease-targeted therapy: prevent or treat myocardial ischemia, prevent or regress left ventricular hypertrophy. Mechanism-targeted therapy (future directions): modify neurohumoral activation using renin, angiotensin, and aldosterone system antagonists (ACE inhibitors, angiotensin II receptor blockade, aldosterone and renin antagonist); endothelin antagonists; nitric oxide agonists; and atrial natruretic peptide agonists; alter intracellular mechanisms; alter extracellular matrix structures.
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PMID:Diastolic Heart Failure. 1109 48


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