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

Patients with hypertension are at increased risk of developing heart failure (HF), but the mechanisms by which hypertension leads to HF have not been clarified [although left ventricular hypertrophy (LVH) is clearly a predictor of an increased risk of HF]. Similarly, although antihypertensive therapy has been shown to reduce the risk of HF in hypertensive patients, it is not known how this benefit is produced and, currently, there is no clear evidence that any class of antihypertensive agent is more effective than any other in this respect. On theoretical grounds, beta-blockers would be expected to be ideal agents for the prevention of HF in hypertensive patients. In addition to control of blood pressure and regression of LVH, they have clear benefits on morbidity and mortality after myocardial infarction (MI), which probably plays a major role in the development of HF in hypertensive patients, and on the prognosis of HF itself. A reduction in long-term mortality after MI has been demonstrated only for non-selective beta-blockers. Carvedilol, a non-selective beta-blocker which also has other ancillary properties including alpha-1-receptor blockade and antioxidant effects and a favourable metabolic profile, may be an appropriate choice for the prevention of HF in hypertensive patients. This is reinforced by the salutary benefits of carvedilol for the reduction in the morbidity and mortality of HF itself.
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PMID:Progression from hypertension to heart failure. Mechanisms and management. 1065 67

BACKGROUND: There is now a wealth of data supporting the use of beta-blockers in heart failure and the additional pharmacological properties of carvedilol are thought to play an important role in the therapeutic efficacy of carvedilol in this disease. METHODS AND RESULTS: Carvedilol is licensed for the treatment of essential hypertension, chronic stable angina, and mild to moderate chronic heart failure. This article provides an up-to-date review of the clinical pharmacology of carvedilol, with particular emphasis on its clinical effects in heart failure. CONCLUSION: Carvedilol is a multiple-action neurohormonal antagonist that offers nonselective beta-blockade, alpha-1 blockade, antioxidant, anti-ischemic mortality, and anti-proliferative properties. In addition to reductions in hospitalization and mortality rates, benefits of carvedilol in heart failure include dramatic improvements in left ventricular function and other parameters of cardiac remodeling.
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PMID:Clinical Pharmacology of Carvedilol. 1068 42

The aim of this update is to review the role of digitalis and betablockers in the treatment of chronic cardiac failure. The role of digitalis is unquestioned in the treatment of chronic cardiac failure complicated by atrial fibrillation resistant to attempts at reduction. Digoxin, with a shorter half-life, is preferred to digitalis. When in sinus rhythm, digoxin is indicated in association with diuretics and angiotensin converting enzyme inhibitors, to improve the quality of life without demonstrable effects on survival. Betablockers now have a recognised place in the treatment of chronic cardiac failure in association with diuretics and angiotensin converting enzyme inhibitors. The compilation of the US-Carvedilol HF Trial have shown a 67% reduction in mortality at 6 months. Carvedilol has been officially approved for use in this indication. Some betablockers are under evaluation, regarding positive results in term of mortality, some clinical trials have been stopped. This review emphasises the changes in prescribing habits of digitalis, and mostly betablockers, in chronic cardiac failure.
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PMID:[Digitalis and beta-blockers: what treatment, what dose and for which patient?]. 1083 84

(1) Carvedilol is the first betablocker to obtain approval in France for the treatment of heart failure. (2) The improvement in haemodynamic parameters was initially documented in three methodologically sound studies involving a total of 156 patients, with follow-up limited to 16 weeks. (3) A placebo-controlled, double-blind trial involving 1,094 patients showed a beneficial impact on overall mortality of 4.6% in absolute terms after a median follow-up of 6.5 months. This benefit was not found in another trial involving 415 patients followed for 19 months on average. Results for symptom-based criteria are conflicting. (4) When treatment is introduced very gradually, adverse effects seem to be minor (malaise) and infrequent. (5) The place of carvedilol in the treatment of heart failure is not yet precisely documented.
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PMID:Carvedilol: new preparation. Encouraging but inadequate data. 1084 56

1. Clinical studies have shown different effects of beta-blockers on the beta-adrenergic system, tolerability and outcome in patients with heart failure. 2. The study examines beta-adrenoceptor-G-protein coupling and intrinsic activity of bucindolol, carvedilol and metoprolol in human ventricular myocardium. 3. Radioligand binding studies ([(125)I]-Iodocyanopindolol) were performed in membrane preparations of human failing and nonfailing myocardium. Functional experiments were carried out in isolated muscle preparations of human left ventricular myocardium from failing hearts. 4. Bucindolol and carvedilol bound non-selectively to beta(1)- and beta(2)-adrenoceptors and exerted guanine nucleotide modulatable binding. Metoprolol was 35-fold beta(1)-selective and lacked guanine nucleotide modulatable binding. 5. All beta-blockers antagonized isoprenaline-induced enhancement of contractility. 6. In preparations in which the coupling of the stimulatory G-protein to adenylate cyclase was facilitated by forskolin, bucindolol increased force of contraction in three and decreased it in five experiments. Carvedilol increased force in one and decreased it in six experiments. Metoprolol decreased force in all experiments by 89. 4+/-2.2% (P<0.01 metoprolol vs carvedilol and bucindolol). The negative inotropic effect of metoprolol was antagonized by bucindolol. 7. It is concluded that differences in intrinsic activity can be detected in human myocardium and have an impact on cardiac contractility. In human ventricular myocardium, bucindolol displays substantially higher intrinsic activity than metoprolol and carvedilol. Bucindolol can behave as partial agonist or partial inverse agonist depending on the examined tissue. 8. Differences in intrinsic activity may contribute to differences in beta-adrenoceptor regulation and possibly to differences in tolerability and outcomes of patients with heart failure.
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PMID:Different intrinsic activities of bucindolol, carvedilol and metoprolol in human failing myocardium. 1088 99

Carvedilol is a beta-adrenoceptor antagonist with multiple actions, which may contribute to superior cardioprotection in heart failure and myocardial infarction. We hypothesized that carvedilol may modulate presynaptic norepinephrine release in the heart. Therefore, we compared the effects of carvedilol (racemate and both enantiomers) and beta1-selective as well as nonselective beta-adrenoceptor blockers on norepinephrine release in isolated perfused rat hearts under normoxic and brief ischemic conditions. Exocytotic release of endogenous norepinephrine was induced by paired electric field stimulations to compare the release before (S1) and after (S2) beta-adrenoceptor blocker application. Metoprolol, bisoprolol, and pindolol (0.1-10 microM) had essentially no effect on exocytotic norepinephrine release under normoxic and ischemic conditions. In contrast, carvedilol exerted a biphasic concentration-response curve (increase followed by suppression) on norepinephrine release. The increase in norepinephrine release was more pronounced with R-carvedilol than with S-carvedilol, indicating an effect independent from beta-receptor antagonism. During ischemia, the facilitatory effect of carvedilol on norepinephrine release was lost, resulting in a concentration-dependent suppression of the release. These results indicate that carvedilol in contrast to classic beta1-selective and -nonselective beta-adrenoceptor blockers has pronounced effects on cardiac norepinephrine release with a remarkable difference between normoxic and ischemic conditions. Whereas a facilitation of norepinephrine release prevailed in normoxia, we observed a suppression of the release in ischemia. It remains to be established whether this unique action of carvedilol on cardiac sympathetic neurotransmission is of clinical relevance.
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PMID:Differential effects of carvedilol on norepinephrine release in normoxic and ischemic heart. 1089 66

Carvedilol has been shown to be beneficial for patients with heart failure, but it is not clear how it should be initiated in routine clinical practice, particularly in the elderly. This study is a retrospective review of 19 patients of age 80+/-4 years with heart failure, who had Carvedilol treatment initiated in a routine outpatient clinic. No patient experienced a worsening of their heart failure or required admission to hospital. There was a mean reduction in heart rate of 11 beats/min. Carvedilol was tolerated by 68% of the patients. Thus, Carvedilol can be safely initiated in a routine outpatient clinic in appropriately selected elderly patients.
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PMID:Experience of commencing Carvedilol in elderly patients with heart failure in a routine outpatient clinic. 1093 90

Carvedilol is a vasodilating beta-blocker and antioxidant approved for treatment of mild to moderate hypertension. angina, and congestive heart failure. Metoprolol is a beta1-selective adrenoceptor antagonist. When carvedilol and metoprolol were recently compared in clinical trials for heart failure, each showed beneficial beta-blocker effects such as improved symptoms, quality of life, exercise tolerance, and ejection fraction, with no between-group differences. When thiobarbituric acid reactive substance (TBARS) levels were measured in serum as an indirect marker of free radical activity, there were also no between-group differences. However, we had noted superior cardioprotection by carvedilol in comparison to metoprolol in ischemia and reperfusion models. We therefore examined antioxidant activity directly in cells and tissues. Here we show that in cultured rat cerebellar neurons, and in brain and heart membranes, carvedilol has far greater antioxidant activity than metoprolol, which is essentially inactive as an antioxidant in these model systems. The antioxidant activity of carvedilol could be explained by a greater degree of lipophilicity, as measured by its ClogP value of 3.841 as contrasted to a ClogP value of 1.346 for metoprolol. Alternatively, the molecular structure of carvedilol favors redox recycling, which the structure of metoprolol does not. Therefore, carvedilol could have additional pharmacologic effects that are favorable for long-term therapy.
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PMID:A comparison of carvedilol and metoprolol antioxidant activities in vitro. 1094 72

Although chronic sympathetic activation provides inotropic and chronotropic support to the failing heart, such activation may also have deleterious effects, including the direct cardiotoxic effects of catecholamines, activation of the renin-angiotensin-aldosterone system and an increase in myocardial oxygen demand. These observations indicate that beta-blockade might be beneficial in the treatment of heart failure. This suggestion is receiving growing support from clinical trials, which show that beta blockade improves the clinical and functional status of patients with heart failure resulting from dilated cardiomyopathy or ischaemic heart disease. These trials have also indicated beta blocking agents are much safer in patients with heart failure than was previously thought, provided that they are introduced at a low dose and titrated carefully. Newer beta blocking agents have ancillary properties that may be important in the treatment of heart failure. Bucindolol and carvedilol have vasodilating effects that may unload the failing heart, and carvedilol also has antiproliferative and antioxidant properties not shared by other beta blocking agents. Carvedilol is the only beta blocking agent that has reduced overall mortality in patients with heart failure in controlled clinical trials, and it also reduces hospitalization and improves the global assessment of patients. A large comparative trial against other beta blocking agents to confirm that these benefits are unique to carvedilol is about to be launched. Further clinical experience is required to determine the optimum use of carvedilol in the treatment of heart failure. The results obtained so far with carvedilol suggest that the management of heart failure is about to undergo a significant change.
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PMID:Beta-adrenergic blockade in the treatment of congestive heart failure. 1094 44

Controlled clinical trials, performed in more than 13,000 patients, have consistently shown the beneficial effects of long-term beta-blocker therapy in patients with chronic heart failure. However, it is not clear whether this is a class effect or if it is specific only for some agents. Beneficial effects on the prognosis of the patients with mild to moderate heart failure have been obtained with metoprolol, bisoprolol, and carvedilol. Metoprolol and bisoprolol are selective for beta(1)-receptors and without ancillary properties, carvedilol, at doses of 25 mg twice daily, blocks beta(1)-, beta(2)-, and a(1)-adrenergic receptors, and has associated antiproliferative and antioxidant activities. These differences are important for the acute hemodynamic effects, but it is still controversial whether they may also influence the long-term effects of therapy. Differently from selective b-blockers, carvedilol blocks all adrenergic receptors, does not upregulate beta1-receptors, decreases cardiac norepinephrine release, and has associated antioxidant effects. These differences may cause a larger increase in left ventricular function, which was significant in some, but not all of the direct comparisons of the two agents. The long-term effects of different beta-blockers on prognosis are currently compared in the Carvedilol or Metoprolol European Trial, in which more than 3000 patients with chronic heart failure have been 1:1 randomized to metoprolol or carvedilol and are going to be followed for more than 2 years.
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PMID:Selective or nonselective beta-adrenergic blockade in patients with congestive heart failure. 1098 Sep


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