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)

Although inhibitors of angiotensin-converting enzyme (ACE) have improved the treatment of chronic heart failure (CHF), mortality related to this disorder remains unacceptably high. Results from studies started more than 25 years ago in Sweden suggested that long-term therapy with beta-blockers could improve hemodynamics and increase survival in patients with CHF; this hypothesis is confirmed by the results of six double-blind, randomized, placebo-controlled trials (MDC, CIBIS, ANZ, US Carvedilol Study, CIBIS II and MERIT-HF) who enrolled about 9000 patients with CHF. In these trials beta-blockers (metoprolol, bisoprolol or carvedilol) where added to the stable usual treatment of each patient (ACE-inhibitors, diuretics, digoxin). Baseline characteristics of patients enrolled into the beta-blocker or placebo arm were similar in all these studies. Specifically the mean patient's age was < 60 years, with a mean left ventricular ejection fraction of 25-26%, 30% of enrolled patients were in NYHA functional class II and 60% in NYHA functional class III, CHF was due to ischemic heart disease in about 60% of patients. The average follow-up for all the trials was 14.5 +/- 5.6 months. On the whole in patients on beta-blocker treatment there is a 33.3% reduction in total mortality rate, a 34.2% reduction in cardiac death rate, a 37.7% reduction in sudden death rate, and a 41.7% reduction in worsening heart failure mortality rate. Moreover, in beta-blocker patients there is a 31.7% reduction in all-cause readmissions to hospital and a 26% reduction in the combined end point (total mortality and hospital readmission). Beta-blockers improved ventricular function but there was no significant improvement in functional capacity. In conclusion, the results of the six trials considered indicate that there is convincing evidence supporting a favorable effect of beta-blockade on the risk of death and readmission to hospital in patients with dilated cardiomyopathy with systolic dysfunction, aged < 70 years, in NYHA functional class II-III. The effects of these drugs in CHF patients a) with normal left ventricular ejection fraction, b) aged > 65-70 years, c) in NYHA functional class IV, and d) with comorbilities such as obstructive lung disease, diabetes, peripheral arterial diseases, require additional study.
 ...
PMID:[The use of beta blockers in heart failure: clinical studies]. 1099 5

Sympathetic activation is a significant predictor of a poor prognosis in heart failure. Excessive stimulation with norepinephrine produces apoptosis, tachycardia and arrhythmias thereby leading to progression of left ventricular dysfunction and worsening of outcome. Beta-blockers reduce morbidity and improve cardiac function. They have been shown to improve survival (MERIT-HF, CIBIS II and US-Carvedilol Trials). A careful uptitration of dosages is achievable with a low rate of side effects. The mechanism of beta-blocker effects in heart failure are cardiac protection from beta1-adrenoceptor overstimulation, antiarrhythmic effects, reduction in heart rate and positive energetic effects or a combination thereof.
 ...
PMID:Treatment of heart failure with beta-blockers. Mechanisms and results. 1119 47

Recent findings on the use of beta-adrenergic blockers in patients with congestive heart failure (CHF) are reviewed. CHF is a progressive, debilitating disease that afflicts 4.6 million patients in the United States. Treatment has traditionally consisted of a diuretic, an angiotensin-converting-enzyme (ACE) inhibitor, and digoxin. Despite advances in ACE-inhibitor therapy, the five-year mortality rate remains nearly 50%. Overstimulation of the sympathetic nervous system is believed to contribute to mortality. Beta-blockers have recently been added to the standard of care for patients with New York Heart Association functional class II or III heart failure. Four randomized, double-blind, placebo-controlled clinical trials were recently completed that addressed the benefits of beta-blockers in CHF. The overall mortality rate was reduced 65% by carvedilol, 34% by metoprolol, and 33% by bisoprolol; all these reductions were significant compared with placebo, and the trials were ended early. Bucindolol, however, did not have a significant effect on mortality. These drugs are hepatically metabolized and may require dosage adjustment in hepatically impaired patients. Decompensation of heart failure is another consideration; a beta-blocker should be added only for patients with stable CHF. Dosages must be slowly adjusted to targeted levels. Adverse effects do not differ significantly among beta-blockers. In addition to their effect on mortality, beta-blockers reduce CHF-related morbidity, such as all-cause hospitalization. Carvedilol, metoprolol, and bisoprolol decrease the mortality and morbidity associated with CHF and can be used with limited adverse effects. The choice among these agents does not affect clinical outcomes; bucindolol, however, has proven ineffective.
 ...
PMID:Current role of beta-adrenergic blockers in the treatment of chronic congestive heart failure. 1188 16

Ischemic heart disease is an important and common contributor to the development of heart failure. Theoretically, all patients with heart failure may benefit from treatment designed to retard progressive ventricular dysfunction and arrhythmias. Patients with ischemic heart disease may also theoretically benefit from the relief of ischemia, the prevention of coronary occlusion, and revascularization. However, there is little evidence to show that the presence or absence of coronary disease modifies the benefits of effective treatments such as angiotensin-converting enzyme inhibitors and beta-blockers. Moreover, there is no evidence that treatment directed specifically at myocardial ischemia or coronary disease alters outcome in patients with heart failure. Treatments aimed at relieving painless myocardial ischemia have not been shown to alter prognosis. Lipid-lowering therapy is theoretically attractive for patients with heart failure and coronary disease; however, theoretical concerns also exist about the safety of such agents, and patients with heart failure have been excluded from large outcome studies very effectively. Some agents, such as aspirin, designed to reduce the risk of coronary occlusion seem ineffective or harmful in patients with heart failure, although warfarin may be safe and possibly effective. There is no evidence yet that revascularization improves prognosis in patients with heart failure, even in patients who are shown to have extensive myocardial hibernation. On current evidence, revascularization should be reserved for the relief of angina. Large-scale, randomized controlled trials are currently underway that are investigating the role of specific treatments targeted at coronary syndromes. The Carvedilol Hibernation Reversible Ischemia Trial: Marker of Success study is investigating the effects of carvedilol in a large cohort of patients with and without hibernating myocardium. The Warfarin and Antiplatelet Therapy in Chronic Heart Failure study is comparing the efficacy of aspirin, clopidogrel, and warfarin. The Heart Revascularization Trial-United Kingdom study is assessing the effect of revascularization on mortality in patients with heart failure and myocardial hibernation. Smaller scale studies are assessing the safety and efficacy of statin therapy in patients with heart failure. Only once the outcomes to these and other planned trials are known can the medical community know how best to treat their patients.
 ...
PMID:What is the optimal medical management of ischemic heart failure? 1125 Nov 29

A programme of four phase III clinical trials carried out in the USA on 1094 patients showed that Carvedilol, associated with the usual bitherapy and eventually with digitalis, reduced the mortality and number of hospital admissions of patients with cardiac failure. These results, transposed to the French population, may be used to evaluate the economic advantages of Carvedilol by developing a cost-effectiveness study which consists in relating the direct expenses (drugs and hospital admissions) of each of the two strategies, with or without Carvedilol, to their respective mortalities. Hospital expenses were estimated with respect to the H.M.G. corresponding to each hospital stay at 1997-1998 values. The cost in the Carvedilol group was 2,823 FF per patient (including 1,491 FF for the drug itself) but 2,056 FF were economised in hospital expenses. With an increased cost of 767 FF but a 50% reduction in mortality corresponding to a difference in mortality of 45@1000, the cost-effectiveness of Carvedilol was 17,040 per life saved and 2,130 FF per additional year of life expectancy. A study of the sensitivity produced even more favourable results of Carvedilol. An evaluation of hospital expenses on the basis of AP-HP data indicates that the addition of Carvedilol is associated with a 4,425 FF reduction in hospital expenses, which makes it a cost saving strategy.
 ...
PMID:[Economic study of carvedilol in heart failure. A cost effectiveness study in France]. 1126 58

Carvedilol is a beta-blocker with ancillary properties. Pilot clinical studies with carvedilol, added to the standard therapy of digoxin, diuretics and ACE inhibitors, showed beneficial effects in mild, moderate and severe heart failure. Patients consistently showed improvement in LV ejection fraction and NYHA functional class. Subsequently large clinical trials showed decreased morbidity and mortality with carvedilol in mild and moderate and more recently, severe heart failure. However, there is little or no improvement in exercise tolerance with carvedilol. The beneficial effects of carvedilol in heart failure are associated with cardiac remodelling. Metoprolol and bisoprolol are selective beta(1)-blockers without ancillary properties. Early studies showed benefits with metoprolol and bisoprolol in heart failure. Large clinical trials established that metoprolol and bisoprolol decreased mortality and morbidity in heart failure. In contrast no benefit has been shown with celiprolol, a selective beta(1)-blocker and beta(2)-stimulant in heart failure. There is a debate as to whether the ancillary properties of carvedilol contribute to its beneficial effect in heart failure, making it a better drug to use than metoprolol. Short-term studies suggested that carvedilol and metoprolol were equivalent in heart failure but short-term is probably not an appropriate way to compare the drugs. A recent long-term study and study in poor responders to metoprolol, suggest that carvedilol may be better than metoprolol in heart failure.
 ...
PMID:Carvedilol versus other beta-blockers in heart failure. 1132 70

Along with the angiotensin-converting enzyme inhibitors (ACEIs), the beta-adrenergic receptor blockers have gradually emerged to be standard in the therapy of heart failure. Individual beta-blockers that have been shown to reduce all-cause mortality in patients with heart failure include bisoprolol, metoprolol and carvedilol. Carvedilol distinguishes from the other beta-blockers as being a non-selective beta(1)- and beta(2)-receptor blocker with (1)-receptor blockade effect and anti-oxidant properties. The drug does not have sympathomimetic activity and has vasodilatory effects attributable to its (1)-receptor blockade property. Experimental and clinical studies have confirmed carvedilol's vasodilator, anti-oxidant and anti-apoptotic properties, which may contribute to its effect in reversing cardiac remodelling in animal models and patients with heart failure. These pharmacological properties render carvedilol a potentially useful agent in the treatment of patients with heart failure. Early studies of carvedilol in heart failure have reported beneficial haemodynamic effects but variable effects on exercise tolerance and clinical well being. The large-scale US Carvedilol Heart Failure Program and the Australian/New Zealand Heart Failure Collaborative Research Group reported beneficial effects of carvedilol on mortality, morbidity and clinical well being in patients with mild-to-moderate heart failure. The recently reported but yet unpublished preliminary results of the COPERNICUS study suggest that carvedilol improves mortality and morbidity in patients with advanced heart failure and severe symptoms. At this time, it is unclear whether the ancillary pharmacological properties of carvedilol can be translated to more superior clinical benefit compared to the other beta-blockers. Preliminary studies examining surrogate end points suggest that carvedilol may improve left ventricular ejection fraction (LVEF) more than metoprolol. More conclusive information regarding their relative effects of clinical outcomes will await the completion of the COMET study, which compares the effect of metoprolol and carvedilol on mortality and morbidity, expected at the end of the year 2002.
 ...
PMID:Carvedilol in the treatment of chronic heart failure. 1133 26

Results of the studies published or reported within the last 2 years provide convincing evidence that beta-blockers can decrease mortality in patients with chronic symptomatic heart failure because of left ventricular systolic dysfunction. The Cardiac Insufficiency Bisoprolol Study (CIBIS)-II and Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) trials showed a 34% reduction in all-cause death with bisoprolol and metoprolol therapy in patients with class II-III heart failure. Data from Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS), with a 35% mortality reduction, extended this benefit to class IV patients treated with carvedilol who do not require intravenous diuretics or positive inotropes. Ongoing beta-blocker studies address new topics, such as treatment of older patients, in whom diastolic heart failure may be more common, and direct comparison of different drugs. Although the use of beta-blockers for heart failure tends to increase, implementation of the knowledge from the trials in clinical practice still remains a challenge.
 ...
PMID:Overview of the results of recent beta blocker trials. 1135 13

Advances in computing have combined with the rapid dissemination of treatment discoveries for diseases of public health importance to create pressure for accelerated promulgation of promising research results to the medical community. The 2 recent examples of the US Carvedilol Heart Failure program and the Evaluation of Losartan In the Elderly (ELITE) study demonstrate the importance of the prospective nature of research design, as well as the consequences of its abandonment. This article explains in nonmathematical terms the rationale for the tenet "first say what you will do, then do what you said" in sample-based research.
 ...
PMID:Random research. 1142 83

Inhibition or reversal of ventricular remodelling in heart failure patients is regarded as of prime importance in the treatment of heart failure and in determining long term outcome. Recent studies have demonstrated that the addition of carvedilol to Angiotensin Converting Enzyme (ACE) inhibitors and other routine heart failure therapy results in a valuable improvement in the clinical status and life expectancy of mild, moderate and severe heart failure patients. ACE inhibitors have become the cornerstone of heart failure therapy. Also, carvedilol in combination with standard therapy (including ACE inhibitors) has demonstrable beneficial effects on left ventricular remodelling. Each new treatment has to be added, this quickly leads to polypharmacy, which may not be necessary and even unwanted in the individual patient, as the pharmacological profile of carvedilol compares favourably to ACE inhibitors, this suggests that it could challenge ACE inhibitors as first-line treatment for heart failure. The CARMEN trial (Carvedilol and ACE-Inhibitor Remodelling Mild Heart Failure EvaluatioN) was designed to compare the effects of carvedilol alone and of carvedilol plus an ACE inhibitor (enalapril) with the effect of an ACE inhibitor alone on different parameters of left ventricular remodelling as well as morbidity and mortality in patients with chronic mild heart failure, thereby allowing conclusions on whether combination therapy may be replaced by the multiple action adrenergic inhibitor carvedilol in the future.
 ...
PMID:The Carvedilol and ACE-Inhibitor Remodelling Mild Heart Failure EvaluatioN trial (CARMEN)--rationale and design. 1150 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>