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

Carvedilol (Dilatrend) blocks beta(1)-, beta(2)- and alpha(1)-adrenoceptors, and has antioxidant and antiproliferative effects. Carvedilol improved left ventricular ejection fraction (LVEF) in patients with chronic heart failure (CHF) in numerous studies. Moreover, significantly greater increases from baseline in LVEF were seen with carvedilol than with metoprolol in a double-blind, randomised study and in a meta-analysis. Carvedilol also reversed or attenuated left ventricular remodelling in patients with CHF and in those with left ventricular dysfunction after acute myocardial infarction (MI). Combined analysis of studies in the US Carvedilol Heart Failure Trials Program (patients had varying severities of CHF; n = 1094) revealed that mortality was significantly lower in carvedilol than in placebo recipients. In addition, the risk of hospitalisation for any cardiovascular cause was significantly lower with carvedilol than with placebo. Mortality was significantly lower with carvedilol than with metoprolol in patients with mild to severe CHF in the Carvedilol Or Metoprolol European Trial (COMET) [n = 3029]. The Carvedilol Prospective Randomised Cumulative Survival (COPERNICUS) trial (n = 2289) demonstrated that compared with placebo, carvedilol was associated with significant reductions in all-cause mortality and the combined endpoint of death or hospitalisation for any reason in severe CHF. All-cause mortality was reduced in patients who received carvedilol in addition to conventional therapy compared with those who received placebo plus conventional therapy in the Carvedilol Post-Infarct Survival Control in LV Dysfunction (CAPRICORN) trial (enrolling 1959 patients with left ventricular dysfunction following acute MI). Carvedilol was generally well tolerated in patients with CHF. Adverse events associated with the alpha- and beta-blocking effects of the drug occurred more commonly with carvedilol than with placebo, whereas placebo recipients were more likely to experience worsening heart failure. In conclusion, carvedilol blocks beta(1)-, beta(2)- and alpha(1)-adrenoceptors and has a unique pharmacological profile. It is thought that additional properties of carvedilol (e.g. antioxidant and antiproliferative effects) contribute to its beneficial effects in CHF. Carvedilol improves ventricular function and reduces mortality and morbidity in patients with mild to severe CHF, and should be considered a standard treatment option in this setting. Administering carvedilol in addition to conventional therapy reduces mortality and attenuates myocardial remodelling in patients with left ventricular dysfunction following acute MI. Moreover, mortality was significantly lower with carvedilol than with metoprolol in patients with mild to severe CHF, suggesting that carvedilol may be the preferred beta-blocker.
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PMID:Carvedilol: a review of its use in chronic heart failure. 1290 89

In 2002, several studies were directed at new developments in the management of heart failure. In the COPERNICUS study, the previously reported benefits of the beta-adrenoreceptor blocker carvedilol regarding morbidity and mortality in patients with mild-to-moderate heart failure were also found in patients with severe heart failure. Carvedilol not only improves survival but when given in addition to conventional therapy, ameliorates the severity of heart failure and reduces the risk of clinical deterioration, hospitalisation and other serious adverse events. The diagnostic value of B-type natriuretic peptide (BNP) in patients with congestive heart failure has been a topic of study for the past five years. Many questions still need to be answered but the results of a study by Maisel et al. show that BNP is not only of diagnostic value but is also important for prognosis and evaluation of therapy. A substudy of the Val-HeFT study focussed on the effects of the angiotensin receptor blocker valsartan on BPN and noradrenaline levels. Valsartan significantly reduced the combined endpoint of mortality and morbidity and improved clinical signs and symptoms in patients with heart failure, if added to prescribed therapy. However, in a post-hoc observation an adverse effect on mortality and morbidity was seen in the subgroup receiving valsartan, an ACE inhibitor and a beta-blocker, which raised concern about the potential safety of this specific combination. And finally, interesting work by Abraham et al. on cardiac resynchronisation through atrial-synchronised biventricular pacing clearly shows that this therapy can produce a significant clinical improvement in patients with moderate-to-severe congestive heart failure and intraventricular conduction delay.
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PMID:New developments in the management of heart failure: a review of the literature in 2002. 1291 46

We studied effects of beta-adrenoblocker carvedilol vs placebo in 60 patients with chronic cardiac failure (CCF) of functional classes III-IV in a 6-month open randomized trial. We examined clinical course, exercise tolerance (a 6 min walk test), endothelial state markers (endothelium-dependent vasodilation, number of circulating endotheliocytes) and activity of systems affecting endothelium (triglycerides, malonic dialdehyde, IL-8, uric acid). The drug was added to conventional therapy (ACE inhibitors, diuretics, cardiac glycosides) in a stable CCF course. Carvedilol group of patients demonstrated a marked trend to reduction of the number of hospitalizations, attenuation of CCF, better tolerance to exercise, lower levels of uric acid (p < 0.05), malonic dialdehyde (p < 0.05) and IL-8 (p = 0.09). There was also wider basal diameter of the brachial artery, and in the diameter at the peak of reactive hyperemia (p = 0.07). The effect was dose-dependent: in patients given 25-50 mg/day of carvedilol there was a trend to a lower circulation of endotheliocytes, triglyceridemia, lipid peroxidation and chronic inflammation. Thus, long-term treatment of CCF with inclusion of standard doses of carvedilol not only improves clinical status of the patients but produces a noticeable endothelioprotective effect.
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PMID:[Endothelial protection in patients with apparent cardiac failure in long-term therapy by carvedilol]. 1293 11

Beta blockers have been shown to prolong survival in chronic heart failure. It is currently a matter of debate whether any beta blocker is superior to the other in terms of improving symptoms, left ventricular function, or prognosis. A number of comparative studies have been performed with metoprolol, a beta1-selective second-generation beta blocker, and carvedilol, a nonselective and vasodilatative third-generation beta blocker. This review will focus on the different pharmacological profiles of carvedilol and metoprolol as well as on the clinical consequences derived from these differences. The results indicate that in some studies carvedilol is superior to metoprolol in improving left ventricular ejection fraction. However, because there is no conclusive evidence that carvedilol is superior to metoprolol in terms of prognosis, it is not justified to substitute metoprolol with carvedilol. Comparative data on mortality reduction are not available before termination of the Carvedilol or Metoprolol European Trial. Nevertheless, the different effects of both beta blockers on the beta-adrenergic system have an impact on tolerability and beta-adrenergic responsiveness and thus exercise tolerance in heart-failure patients.
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PMID:Beta-blocker treatment of chronic heart failure: comparison of carvedilol and metoprolol. 1456 43

The CAPRICORN (Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction) trial established that the beta-blocker carvedilol reduces the risk of death in patients with left ventricular dysfunction post myocardial infarction, whether or not the infarct is complicated by clinical heart failure. Thus, the utility of the beta-blocker carvedilol is confirmed in the modern era as an adjunct to revascularization, angiotensin-converting enzyme inhibitors, aspirin, and statins. In addition, the results prompt us to review the prior studies of beta-blockers postinfarction. Critical review of CAPRICORN and earlier beta-blocker studies suggests that specific beta-blockers should be matched to specific clinical scenarios. The COMET (Carvedilol or Metoprolol European Trial) study reinforces this view by establishing that beta-blockers are not simply interchangeable agents.
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PMID:New evidence from the CAPRICORN Trial: the role of carvedilol in high-risk, post-myocardial infarction patients. 1456 31

Carvedilol and metoprolol are beta(1)-adrenoceptor antagonists that decrease mortality in heart failure. It is not clear whether the ancillary properties, which carvedilol has but metoprolol does not have, contribute to the beneficial effect. The Carvedilol Or Metoprolol European Trial (COMET) compared metoprolol tartrate (mean daily dose 85 mg) and carvedilol (41.8 mg) in patients with heart failure. All-cause mortality was less in the carvedilol than the metoprolol group, indicating that at these doses, carvedilol has a mortality benefit over metoprolol. However, the beta(1)-adrenoceptor blocking activity of metoprolol tartrate (assessed by a decrease in heart rate) was slightly less than with carvedilol in COMET and less than that observed in previous mortality studies with metoprolol, suggesting that the use of metoprolol tartrate was not optimal in COMET.
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PMID:Has COMET solved the controversy as to whether carvedilol is better than metoprolol in heart failure? 1285 93

The Carvedilol or Metoprolol European Trial (COMET; Lancet 2003; 362:7-13) found that in patients with heart failure, survival appears to be better with carvedilol than with immediate-release metoprolol tartrate. Whether the target doses used were equivalent (carvedilol 25 mg twice daily vs metoprolol tartrate 50 mg twice daily) has been debated, but the COMET trial shows that drugs in the same class do not necessarily have the same effects. Given the overwhelming evidence of the benefit of carvedilol, metoprolol succinate, and bisoprolol in patients with heart failure, we should all strive to increase the use of these drugs in appropriate doses.
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PMID:In heart failure, all beta-blockers are not necessarily equal. 1468 87

Until recently, beta-blocking drugs were considered to be contraindicated in patients with chronic heart failure. However, several well-conducted randomised clinical trials have now proven otherwise. Yet, it was still not clear whether nonselective alpha-, beta 1- and beta 2-receptor blockade with carvedilol would be superior to selective beta 1-receptor blockade with metoprolol. One of the studies ('Carvedilol or metoprolol European trial' (COMET)) demonstrated a statistically significant 17% reduction of all-cause mortality with carvedilol. Although striking, the results may have been influenced by differences in blood pressure and heart rate, as well as the short-acting formula of metoprolol that was used. Furthermore, the 'Carvedilol hibernation reversible ischaemia trial; marker of success' (CHRISTMAS) study demonstrated myocardial hibernation in the majority of ischaemic heart-failure patients, and showed beneficial effects on left-ventricle function with carvedilol in both hibernated and non-hibernated patients. Despite this and the rest of the overwhelming evidence, at present only a minority of eligible chronic heart-failure patients are treated with beta-blockers.
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PMID:[Beta-blocking drugs indicated in patients with heart failure]. 1518 27

Controlled clinical trials performed in more than 13 000 patients have, to date, consistently shown the beneficial effects of long term beta-adrenoceptor antagonist (beta-blocker) therapy in patients with chronic heart failure. It is not clear whether this represents a class effect or whether it is specific only to some agents. Beneficial effects on the prognosis of patients with mild to moderate heart failure have been shown with metoprolol, bisoprolol, and carvedilol. These beta-blockers, however, differ in their pharmacologic characteristics. Metoprolol and bisoprolol are selective for beta(1)-adrenergic receptors and are devoid of ancillary properties. Carvedilol, at a dosage of 50 mg/day, blocks all beta(1)-, beta(2)-, and alpha(1)-adrenergic receptors, and it has associated antiproliferative and antioxidant activities. These differences cause a varied acute hemodynamic response, with a reduction in cardiac output and a tendency toward a rise in pulmonary wedge pressure with selective agents and no change in cardiac output and a slight decrease in pulmonary pressures with carvedilol. Accordingly, when the therapy is started, the most frequent adverse effects are worsening heart failure with metoprolol and bisoprolol, and hypotension and dizziness with carvedilol. It remains controversial whether these differences also influence the long term effects of therapy. Carvedilol may provide a more comprehensive blockade of the cardiac adrenergic drive than selective beta-blockers because it does not upregulate beta(1)-adrenergic receptors, blocks all adrenergic receptors and decreases cardiac norepinephrine release. These properties may lead to a larger increase in left ventricular function and a lack of improvement in maximal exercise capacity with carvedilol, compared with selective beta-blockers. It is, however, unclear whether these differences also influence patient outcome. The long term effects of different beta-blockers on prognosis are currently being compared in the Carvedilol or Metoprolol European Trial (COMET) in which more than 3000 patients with chronic heart failure have been randomized in a 1 : 1 ratio to receive metoprolol or carvedilol.
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PMID:Beta-blockade in heart failure: selective versus nonselective agents. 1472 47

Atrial fibrillation (AF) is present in a significant number of patients with heart failure (HF) caused by left ventricular systolic dysfunction and is associated with increased morbidity and mortality. The deleterious interaction of AF and HF is mediated through a number of mechanisms including hemodynamic alterations and activation of the sympathetic nervous system. Beta-blockers have been shown to improve symptoms and survival in patients with HF. In addition, beta-blockers have been used in patients with AF, primarily for rate control. A retrospective analysis of the U.S. Carvedilol Heart Failure Trial demonstrated that carvedilol improves outcomes in the high-risk subgroup of patients with HF and concomitant AF.
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PMID:Beta blockers improve outcome in patients with heart failure and atrial fibrillation: U.S. carvedilol study. 1473 19


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