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

To determine the acute effects of carvedilol (beta-blocker) on cardiovascular and renal function and its pharmacokinetics in dogs. Fifteen mature mongrel dogs (7-15 kg) of both sexes were used in these experiments. Eight dogs served as controls, and seven dogs served as iatrogenic mitral regurgitation (MR) experimental animals. Carvedilol (0.2, 0.4, and 0.8 mg/kg, P.O.) was administered, and the blood carvedilol concentration was analyzed by reverse-phase high-performance liquid chromatography. The response to isoproterenol or phenylephrine was also evaluated. Isoproterenol (0.025 microg/kg/min) was infused via the saphenous vein for 5 min, and phenylephrine (5 microg/kg) was injected with carvedilol (0.2, 0.4 mg/kg) or placebo for 4 days. The heart rate and arterial blood pressure were measured, and LV fractional shortening was measured by echocardiography. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by intravenous infusion of sodium thiosulfate and sodium para-aminohippurate. Carvedilol (0.2 mg/kg) decreased the heart rate, whereas renal function, arterial blood pressure, and left ventricular contractile function were not affected. Carvedilol (0.4 mg/kg) decreased heart rate, blood pressure, and renal function. The tachycardic response to isoproterenol was significantly diminished for 36 hr by 0.4 mg/kg carvedilol. Carvedilol 0.2 mg/kg inhibited this effect for 24 hr. Thus, it is necessary to titrate the dosage of carvedilol, it should be initiated at less than 0.2 mg/kg and titrated up to 0.4 mg/kg for heart failure dogs.
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PMID:Cardiovascular and renal effects of carvedilol in dogs with heart failure. 1213 Aug 29

During the past 15 years, the pathophysiological concept of heart failure as a neurohormonal disease has influenced heart failure therapy substantially. ACE-inhibitors have become the mainstay of heart failure therapy. In addition, beta blocker evolved to be effective in improving survival in this disease. Recently, the COPERNICUS study established the efficacy of carvedilol in severe heart failure and extended the benefits of this drug first observed in patients with mild and moderate symptoms to those with advanced disease. In this study, carvedilol resulted in a significant reduction of all-cause mortality and combined mortality and hospitalization, the frequency of hospitalizations, the risk of repeated hospitalizations, the number of days in hospital, the average duration of each admission and the utilization of treatments and procedures for heart failure. Carvedilol was well tolerated, improved the sense of well-being, was associated with a lower risk of a serious adverse event, particularly one related to the progression of heart failure and fewer patients requiring withdrawal of treatment for an adverse event. These favourable results were equally seen in all subgroups. Carvedilol treatment was even cost-effective in severe disease. Therefore, this new therapeutic option should be available to all patients with symptomatic systolic heart failure.
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PMID:[Beta blockers in heart failure therapy with special reference to the COPERNICUS Study]. 1222 56

Patients with chronic heart failure have increased sympathetic nervous system activity that contributes to deterioration of cardiovascular function over time. Long-term beta-blocker therapy prevents such deterioration through inhibition of this neurohormonal pathway. The impressive survival data collected from several large studies have made beta-blockers a component of standard therapy for New York Heart Association class II to III heart failure. Although there are differences in the pharmacological properties of the beta-blockers shown to improve morbidity and mortality in heart failure, there is little evidence to suggest that such properties constitute any major advantages in clinical outcome. Carvedilol and extended-release metoprolol succinate are 2 beta-blockers currently approved in the United States for the treatment of patients with heart failure. Both agents have shown similar risk reductions in overall and cause-specific mortality; however, no outcome data from a comparative trial are available to support the use of one agent over the other. Regardless of the agent chosen, appropriate dosing and titration of beta-blockers are essential for successful therapy.
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PMID:Beta-blockers in chronic heart failure: considerations for selecting an agent. 1244 May 56

Beta-adrenergic blocking drugs have been shown to improve survival and well-being of patients with mild to moderate heart failure. In more advanced heart failure, the relationship between the short-term hemodynamic support afforded by activation of the sympathetic nervous system and the harm that results from excess sympathetic activation is more complex. Not all studies of beta-adrenergic blocking drugs or antiadrenergic therapy have shown benefit. The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial has revealed that the combined nonselective beta-adrenergic and a-adrenergic receptor blocking drug carvedilol produces an important salutary effect on the natural history of advanced heart failure. Mortality was reduced by 35% in the carvedilol group, from an annual (Kaplan-Meier) rate of 18.5% to 11.4%. All-cause hospitalizations were reduced by 20% and hospitalization from heart failure by 33%. Even amongst the subgroups at highest risk, no subpopulation could be identified that did not appear to benefit. The trial supports extending the population of those with chronic heart failure who should be routinely treated with beta-adrenergic blocking drugs (in addition to angiotensin-converting enzyme inhibition therapy) to patients with more advanced disease.
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PMID:Beta-adrenergic blocking drugs in severe heart failure. 1244 58

The utilization of b-blockers for the treatment of heart failure in the United States is inadequate despite the available data and the current guidelines that support their use. The ongoing Initiation Management Predischarge Process for Assessment of Carvedilol Therapy for Heart Failure (IMPACT-HF) study was designed to determine if initiation of beta-blockade prior to hospital discharge is safe and effective in improving the 60-day use of beta-blockers in patients with heart failure. IMPACT-HF is a community-based, multicenter, open-label trial of 375 heart failure patients randomized to carvedilol initiated before their hospital discharge or to usual care (Heart Failure Society of America guidelines that recommend waiting 2-4 weeks after hospitalization for heart failure before initiating beta-blocker therapy). The entry criteria are nonrestrictive to ensure inclusion of patients reflective of the general heart failure population. The primary endpoint of the study is the number of patients treated with any beta-blocker at 60 days. A concurrently ongoing pilot registry will enroll 550 patients, admitted with exacerbated heart failure, in three phases to collect demographic, clinical, treatment patterns, and outcome data. The trial will test the tolerability of beta-blocker initiation in the hospital setting, develop strategies to improve the use of evidence-based medicine in clinical practice, and explore the patient's course from hospital admission through discharge and up to 60 days. The trial data will determine if in-hospital initiation of beta-blocker therapy is effective at improving the long-term use of pharmacologic agents proven to reduce morbidity and mortality.
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PMID:The Initiation Management Predischarge Process for Assessment of Carvedilol Therapy for Heart Failure (IMPACT-HF) Study: design and implications. 1244 62

Results of drug treatment of 51 patients (41 men, 10 women) aged 35-86 years (mean age 62 years) included into COPERNICUS trial are presented. All patients had compensated NYHA class IV chronic heart failure and left ventricular ejection fraction less than 25%. For at least 2 months the patients received therapy with diuretics and angiotensin converting enzyme inhibitors (84%) or angiotensin receptor blockers (16%) and then were randomized to either carvedilol or placebo. Average duration of follow-up was 17 months. Carvedilol was well tolerated both during dose titration and during maintenance therapy. Addition of carvedilol to standard therapy of patients with severe heart failure was associated with increase of average ejection fraction from 21.7 to 30.3%. Rates of cardiovascular and sudden deaths, risk of hospitalization among carvedilol treated patients were 25, 33 and 57% less than among patients subjected only to standard therapy.
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PMID:[Long term use of a non-selective beta-blocker with vasodilating properties carvedilol in patients with severe heart failure]. 1249 64

Beta-adrenergic stimulation and the resultant Ca(2+) load both seem to be associated with progression of heart failure as well as hypertrophy. Because the alpha(1)-, beta(1,2)-blocker, carvedilol, has been shown to be outstandingly beneficial in the treatment of heart failure, its direct effects on intracellular calcium ion concentration ([Ca(2+)](i)), including antagonism to isoproterenol, in ventricular myocytes were investigated and then compared with a selective beta(1)-blocker, atenolol, and a non-selective beta(1,2)-blocker, timolol. At 1-300 nmol/L, carvedilol decreased the amplitude of [Ca(2+)] (i) by approximately 20% independently of its concentration, which was a similar effect to timolol. All the beta-blockers at 10 nmol/L decreased the amount of cAMP, but atenolol had the least effect. Carvedilol in the micromol/L order further diminished the amplitude of [Ca(2+)](i) transients, and at 10 micromol/L increased the voltage threshold for pacing myocytes. These effects were not observed with timolol or atenolol. L-type Ca2+ currents (I(Ca)) were decreased by carvedilol in the micromol/L order in a concentration dependent manner. As for the beta-antagonizing effect, the concentrations of carvedilol, timolol, and atenolol needed to prevent the effect of isoproterenol by 50% (IC(50)) were 1.32, 2.01, and 612 nmol/L, respectively. Furthermore, the antagonizing effect of carvedilol was dramatically sustained even after removal of the drug from the perfusate. Carvedilol exerts negative effects on [Ca(2+)](i), including inhibition of the intrinsic beta-activity, reduction of I(Ca) in the micromol/L order, and an increase in the threshold for pacing at > or =10 micromol/L. Data on the IC(50) for the isoproterenol effect suggest that carvedilol could effectively inhibit the [Ca(2+)](i) load induced by catecholamines under clinical conditions.
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PMID:Characteristic effects of alpha1-beta1,2-adrenergic blocking agent, carvedilol, on [Ca2+]i in ventricular myocytes compared with those of timolol and atenolol. 1252 Jan 58

Carvedilol is a cardiovascular drug of multifaceted therapeutic potential, with beta-blocker and vasodilatative activity. These actions confer to the above mentioned betablocker some beneficial properties on several processes involving cardiovascular system. Carvedilol provides haemodynamic, antiischemic, antiproliferative and antiarrhytmic benefits, for its antioxidant neurohumoral and electrophysiological effects. All these actions provide the basis for usefulness of the drug in the treatment of hypertension, coronary heart disease, and congestive heart failure. In this review we report the beneficial properties of Carvedilol and we analyze the rational clinical use of this betablocker taking special attention on recent clinical trial in heart failure where it appears an evidence supporting an important, favourable effect of the drug.
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PMID:Carvedilol: something else than a simple betablocker? 1277 5

Carvedilol is a multiple action, non-specific, adrenergic beta-blocker, licensed for the treatment of mild, moderate and severe chronic heart failure. This article considers the evidence for using beta-blockers in general, and carvedilol in particular, in the treatment of heart failure. Evidence suggests that carvedilol should be considered as an alternative first-line initiation therapy.
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PMID:Use of carvedilol in the treatment of heart failure. 1278 38

While beta-adrenergic blockers have been used for decades in a variety of cardiovascular illnesses, they have traditionally been avoided in chronic heart failure. In spite of significant advances in management, mortality in patients suffering from heart failure remains unacceptably high and new therapies are urgently needed. Recently, several large clinical trials have shown a significant reduction in both morbidity and mortality in heart failure patients when beta-blockers are added to standard therapy. While further investigation is warranted in certain subgroups, the use of beta-adrenergic blockers in New York Heart Association (NYHA) class II to IV heart failure should now be considered routine. The purpose of this article is to outline and review the five major clinical trials of beta-blocker therapy in chronic heart failure; the US Carvedilol heart failure Program (USCP), the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), the Metoprolol CR/XL Randomized Intervention Trial in chronic Heart Failure (MERIT-HF), the Beta-blocker Evaluation of Survival Trial (BEST) and the Carvedilol Prospective Randomized Cumulative Survival trial (COPERNICUS), and to aid the reader in the selection of appropriate candidates for beta-blocker therapy.
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PMID:Use of beta-blockers in congestive heart failure. 1284 68


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