Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several truly "landmark' studies were presented during the 45th Annual Scientific Session of the American College of Cardiology (ACC). This report reviews studies of markers of atherosclerosis and some of the trials in endothelial dysfunction (TREND), lipid lowering (CARE), coronary angioplasty and unstable angina (EPILOG, CAPTURE, RESTORE), acute myocardial infarction (HERO, GUSTO 11b), post-myocardial infarction (EMIAT, CAMIAT), and heart failure (DIG trial).
 ...
PMID:Conference review: scientific session of the American College of Cardiology 1996. 875 69

Digitalis has been used for more than 250 years, but its role in the treatment of chronic heart failure has been intensively investigated only during the past two decades. Digoxin increases cardiac output both at rest and during exercise, alone or in combination with ACE inhibitors, and these hemodynamic effects are sustained during chronic therapy. A daily dose of digoxin that achieves a serum concentration of approximately 1.2 ng/ml is associated with a significant improvement in central hemodynamics, particularly in patients with impaired cardiac function despite pretreatment with diuretics and ACE inhibitors. Acute administration of digoxin in patients with chronic heart failure has an immediate sympathoinhibitory effect, and chronic therapy is associated with a sustained decrease in serum norepinephrine concentration. Discontinuation of digoxin in patients with chronic heart failure resulted in hemodynamic deterioration, which was reversed when the drug was readministered. Randomized withdrawal of digoxin in patients receiving only diuretics (PROVED study), or its withdrawal in patients receiving diuretics and ACE inhibitors (RADIANCE study), was associated with worsening of the clinical evidence of heart failure and a decrease in left ventricular systolic function in both studies. In the only large-scale, placebo-controlled mortality study reported thus for (DIG Trial), 7788 patients received standard drug treatment for chronic heart failure in addition to either digoxin or placebo. Digoxin had no impact on survival over the 37 months of follow-up, but the incidence of hospitalizations due to worsening heart failure was significantly reduced in patients receiving the drug compared with those receiving placebo.
 ...
PMID:Digoxin therapy in chronic heart failure. 921 Oct 21

The evidence supporting the efficacy of digoxin in patients with heart failure who are in sinus rhythm is substantial. Digoxin improves hemodynamics, exercise capacity, symptoms, and quality of life and reduces hospitalizations. All of this is accomplished with a drug that is very inexpensive and can be given once daily. Its safety has been established through the DIG trial. Although digoxin does not decrease mortality beyond that of diuretics and ACE inhibitors, it does not increase mortality, unlike many positive inotropes. Furthermore, digoxin, in addition to ACE inhibitors and a diuretic, decreases the hospitalization rate due to worsening of heart failure. From a managed care perspective, as well as that of the patient, this is of enormous benefit. A pharmacoeconomic analysis estimated that continuation of digoxin in patients with stable congestive heart failure could save the healthcare system an estimated $ 400 million, based on costs from one hospital. The issue is not whether to use digoxin in these patients, but rather, how early to initiate therapy. From some of the recent data in patients with systolic dysfunction and mild heart failure, as well as knowledge of the neurohormonal activation that occurs early in these patients, it could be suggested that early use of neurohormonal modulators, including digoxin, would decrease the progression of heart failure. Thus, rather than waiting for symptoms despite optimal doses of an ACE inhibitor and diuretic, as suggested by the AHCPR practice guideline for heart failure, initiation of digoxin therapy in patients as early as NYHA class II at a dosage that will achieve a serum concentration of 1.0 ng/mL or less should occur. With the understanding of digoxin's effect on the neurohormonal systems, its role in patients with preserved systolic function needs to be reexplored. The debate can now focus on asymptomatic patients or those with preserved systolic function. Could these patients benefit from therapy with digoxin as well?
 ...
PMID:Is there an expanded role for digoxin in patients with heart failure and sinus rhythm? A protagonist viewpoint. 922 52

Angiotensin converting enzyme (ACE) inhibitors are associated with a greater reduction in mortality in non-ischaemic cardiomyopathy than in ischaemic cardiomyopathy after the results of the V-HeFT-II and SOLVD trials in symptomatic patients. However, a recent analysis of the global, symptomatic and therapeutic, results of the SOLVD trials, demonstrated a similar reduction in mortality with ACE inhibitors in ischaemic and non-ischaemic cardiomyopathies. Moreover, after myocardial infarction, the beneficial effects of ACE inhibitors have been well established in patients with left ventricular dysfunction. Betablockers, especially bisoprolol in the CIBIS-I trial, also seem to be more effective in non-ischaemic cardiomyopathy. However, CIBIS-II and the US Carvedilol Heart Failure Trial Program clearly showed that the benefits of betablockade were identical whether ischaemic or not. The beneficial effects of betablockers in the post-infarction period are more marked when left ventricular dysfunction is severe. The PROVED and RADIANCE trials suggest that digitalis is more effective in non-ischaemic cardiomyopathy. These results were not confirmed by the DIG trial which showed a significant reduction in the combined criterion, mortality and hospital admission for aggravation of cardiac failure, both in ischaemic and in non-ischaemic cardiomyopathy. However, the use of digitalis should be prudent during ischaemic cardiomyopathy, the neutral effect on global mortality in the DIG trial masking divergent results with a tendency to reducing mortality due to aggravation of cardiac failure and a significant increase of other causes of cardiac death, especially from myocardial infarction and arrhythmias. Amiodarone could also be useful in non-ischaemic cardiomyopathy. The reduction in risk of death in the GESICA study, which comprised 60% of patients with non-ischaemic cardiomyopathy, contrasting with the absence of an effect with this molecule in the STAT-CHF trial which only comprised 29% of patients with non-ischaemic cardiomyopathy. The new generation of calcium antagonists could also be more effective in non-ischaemic cardiomyopathy. Although amlodipine significantly reduced mortality in the PRAISE trial in non-ischaemic cardiomyopathy, there was no favourable effect with felodipine in the V-HeFT-III tria. Finally, if in the earlier studies oral anticoagulants were more effective in non-ischaemic cardiomyopathy, the recent results of the SOLVD trial showed that warfarin decreased the mortality in both ischaemic and non-ischaemic cardiomyopathy. The value of anti-aggregant therapy is not questioned in coronary artery disease, but its role in dilated cardiomyopathy has not yet been established. In conclusion, apart from the use of digitalis which must be prudent in post-infarction cardiomyopathy or in patients with ventricular arrhythmias, the treatment of cardiac failure differs little with respect to its ischaemic or non-ischaemic aetiology, and should be based on the NYHA (New York Heart Association) classification.
 ...
PMID:[Treatment of cardiac insufficiency: does treatment depend on whether its cause is ischemic or idiopathic?]. 1041 Aug 11

Since its introduction in 1785, digitalis has been the cornerstone in the treatment of heart failure, although there during the last 20 years have been an increasing number of critical voices questioning its use in patients with sinus rhythm. In 1997 the Digitalis Investigation Group published the so far largest randomized trial on the use of digoxin in patients with heart failure (DIG-trial). All the included patients had sinus rhythm, and all received an ACE-inhibitor. Digoxin had no effect on mortality, but caused a decrease in hospitalizations. Based on the DIG-study, several minor clinical trials and two large withdrawal studies (RADIANCE and PROVED) it now seems clear that digoxin still has a role in the management of heart failure, not only in patients with atrial fibrillation, but also in patients with sinus rhythm.
 ...
PMID:[Is digoxin effective in the treatment of heart insufficiency in patients with sinus rhythm?]. 1048 4

The role of digitalis in the treatment of patients with heart failure is still being debated. The DIG study, a trial which enrolled about 6800 patients with the aim at overcoming the doubts on efficiency and safety of digoxin, showed a neutral effect on mortality but there was a statistically significant decreased risk of hospitalization due to worsening heart failure in the digoxin group compared to the placebo group. The trial disclosed several problems about patient selection (many patients were on digitalis before the start of the trial), digoxin dosage, which seemed to be high, and about the true reported beneficial effects of this therapy. Finally the data available do not permit any evaluation on the use of beta-blockers and the association between digitalis and beta-blockers considering the properties of these drugs in suppressing orthosympathetic activation.
 ...
PMID:[Use of digitalis in chronic heart failure: an unresolved problem?]. 1121 75

Digitalis glycosides exert a positive inotropic effect, i.e. an increase in myocardial contractility associated with a prolongation of relaxation period, and glycosides lower the heart rate (negative chronotropic), impede stimulus conduction (negative dromotropic) and promote myocardial excitability (positive bathmotropic). They seem to influence the activities of both the vagal and the sympathetic systems. Digitalis glycosides that belong to different substance classes are closely comparable concerning pharmacodynamics but differ substantially in regard to pharmacokinetics. Digoxin and its derivatives are less lipophilic, show lower protein binding and shorter half-life, are mainly eliminated via the kidney and accumulate rather rapidly in cases of insufficient kidney function. Digitoxin is highly lipophilic and extensively bound to plasma proteins, has a longer half-life, is mainly eliminated in the metabolized state via urine and faeces and does not accumulate in kidney dysfunction. As a result of a more stable pharmacokinetic profile, the incidence of toxic side effects seems to be lower with digitoxin than with digoxin. Since the beginning of the 1990s, the antagonists of the RAAS qualified as the standard treatment for congestive heart failure, often in combination with diuretics, vasodilators or beta-antagonists. However, the important role of digitalis glycosides as therapeutic comedication or alternative was never denied, especially in atrial fibrillation with tachycardia. The PROVED and RADIANCE trials proved a detrimental effect of the withdrawal of digoxin therapy on exercise capacity, left-ventricular ejection fraction and clinical symptoms. The DIG trial revealed that digoxin comedication in sinus rhythm patients with congestive heart failure was associated with a lower morbidity (as taken from death or hospitalization because of worsening heart failure) and an unchanged overall mortality--being a unique feature among the available inotropic drugs. Comparable studies for digitoxin have not yet been performed but, because of its higher pharmacological stability, it might well be associated with even more advantages in this regard than digoxin.
 ...
PMID:Treatment of congestive heart failure--current status of use of digitoxin. 1152 33

Despite the introduction of a variety of new classes of drugs for the management of heart failure, digoxin continues to have an important role in long-term outpatient management. A wide variety of placebo-controlled clinical trials have unequivocally shown that treatment with digoxin can improve symptoms, quality of life, and exercise tolerance in patients with mild, moderate, or severe heart failure. These benefits are evident regardless of the underlying rhythm (normal sinus rhythm or atrial fibrillation), etiology of the heart failure, or concomitant therapy (eg. ACE inhibitors). Unlike other agents with positive inotropic properties, digoxin does not increase all-cause mortality and has a substantial benefit in reducing heart failure hospitalizations. Consensus guidelines have recently been published by the Heart Failure Society of America and the American College of Cardiology/American Heart Association, and they contain the following recommendations for digoxin treatment: 1. Digoxin should be considered for the outpatient treatment of all patients who have persistent symptoms of heart failure (NYHA class II-IV) despite conventional pharmacologic therapy with diuretics, ACE inhibitors, and a beta-blocker when the heart failure is caused by systolic dysfunction (the strength of evidence = A for NYHA class II and III; strength of evidence = C for NYHA class IV). 2. Digoxin is not indicated as primary treatment for the stabilization of patients with acutely decompensated heart failure. (Strength of evidence = B). Digoxin may be initiated after emergent treatment of heart failure has been completed in an effort to establish a long-term treatment strategy. 3. Digoxin should not be administered to patients who have significant sinus or atrioventricular block, unless the block has been treated with a permanent pacemaker (strength of evidence = B). The drug should be used cautiously in patients who receive other agents known to depress sinus or atrioventricular nodal function (such as amiodarone or a beta-blocker) (strength of evidence = B). 4. The dosage of digoxin should be 0.125-0.25 mg daily in the majority of patients (strength of evidence = C). The lower dose should be used in patients over 70 years of age, those with impaired renal function, or those with a low lean body mass. Higher doses (eg, digoxin 0.375-0.50 mg daily) are rarely needed. Loading doses of digoxin are not necessary during initiation of therapy for patients with chronic heart failure. 5. Serial assessment of serum digoxin levels is unnecessary in most patients. The radioimmunoassay was developed to assist in the evaluation of toxicity, not the efficacy of the drug. There appears to be little relationship between serum digoxin concentration and the drug's therapeutic effects. 6. Digoxin toxicity is commonly associated with serum levels >2 ng/mL but may occur with lower digoxin levels if hypokalemia, hypomagnesemia, or hypothyroidism coexist. Likewise, the concomitant use of agents such as quinidine, verapamil, spironolactone, flecainide, and amiodarone can increase serum digoxin levels and increase the likelihood of digoxin toxicity. 7. For patients with heart failure and atrial fibrillation with a rapid ventricular response, the administration of high doses of digoxin (>0.25 mg daily) for the purpose of rate control is not recommended. When necessary, additional rate control should be achieved by the addition of beta-blocker therapy or amiodarone (strength of evidence = C). If amiodarone is added, the dose of digoxin should be reduced. Digitalis preparations are now entering their fourth century of clinical use for the treatment of chronic heart failure symptoms. Its clinical efficacy can no longer be doubted and its safety has been verified by the multicenter DIG trial. Future advances in pharmacogenetics should facilitate identification of those patients most likely to benefit from its pharmacologic effects.
 ...
PMID:Digoxin remains useful in the management of chronic heart failure. 1269 28

No relevant sex-based differences in hemodynamic parameters have been described until now but the course of any heart disease may be modified by factors that act differently in men and women. In a study comparing the incidence of heart disease and patient survival over the past 50 years, the incidence of heart failure was found to have declined in women but not in men. With increased sodium excretion and obesity, the hazard ratios for cardiovascular mortality were higher in women. A post-hoc subgroup analysis of the DIG study was conducted to assess potential sex-based differences in the effect of digoxin. The authors conclude that digoxin therapy is associated with an increased risk of death in women (P = 0.34). The comparison of the effects of digoxin was limited simply to gender only and no other subgroup analyses were preformed although the characteristics of the patients show significant differences in more than 20 parameters. Hence, the conclusion of these authors can hardly be accepted. Contrary to these partly conflicting data, the primary results from the Women's Health Initiative randomized controlled trial focused on defining the risks and benefits of hormone replacement in postmenopausal women give an unambiguous answer: combined estrogen/progestin therapy should not be initiated or continued for the primary prevention of coronary heart disease, furthermore, it increases the risks of cardiovascular disease, breast cancer, venous thromboembolism and biliary tract surgery.
 ...
PMID:[New aspects in clinical cardiology: sex-based differences in cardiovascular morbidity and mortality]. 1284 Nov 18

The general profile of women with cardiac failure differs from that of the male population, especially with respect to aetiology and prognosis. Women are often older, have preserved systolic function more often and a higher incidence of risk factors such as hypertension and diabetes. Moreover, global mortality is lower in women. From the therapeutic point of view, women with symptomatic left ventricular dysfunction probably benefit from ACE inhibitors but those with asymptomatic dysfunction have no reduction in mortality with this class of drugs. In addition, treatment with ACE inhibitors is usually interrupted in women because of a higher incidence of secondary effects. The poorer tolerance could be explained by the profile of women with cardiac failure. The large scale multicentre trials with betablockers included very few women. In MERIT-HF, in which there was a large number of women (23%), the female subgroup was the only one in which a benefit in mortality was not demonstrated. However, a retrospective analysis of the data of this subgroup plus a meta-analysis of all trials with betablockers does show improved mortality with this class of drugs in women. In a retrospective study of the DIG study, there seems to be a difference in the effects of digoxin between men and women; the prescription of digoxin is associated with a higher overall mortality in women. Finally, women seem to require diuretics more often than do men. There are many explanations for the differences observed in therapeutic responses between men and women. The role of sex hormones is often evoked, although it has never been clinically proved. The treatment of heart failure in women should take clinical and biological factors specific to women into account and may explain the relative inefficacy of certain forms of treatment.
 ...
PMID:[Response to drug therapy of cardiac failure according to gender]. 1566 63


1 2 Next >>