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

There is a clear relationship between anaemia and cardiovascular risk in chronic renal failure (CRF) patients. Left ventricular hypertrophy (LVH) is present in about three-quarters of patients starting dialysis, and is a strong predictor of mortality. Anaemia contributes to the development of LVH, mainly via increased cardiac output. In some patients, anaemia results in an increase in LV mass, while in others it also results in LV end-diastolic volume dilatation. These changes increase the risk of arrhythmias, myocardial infarction and myocardial fibrosis. The lower the haemoglobin, the more likely it is that LVH and heart failure will develop. Furthermore, a haemoglobin of < 11 g/dl is associated with increased morbidity and mortality. Partial correction of anaemia with epoetin leads to a partial, but not complete, reversal of LVH. One large prospective study (Lombardy Registry) found that epoetin treatment was accompanied by a 30% reduction in crude relative risk of mortality. A progressive reduction in the relative risk of general and cardiovascular mortality was found with increasing haematocrit, with and without adjustment for co-morbid conditions. Mean hospitalizations also decreased with increasing haematocrit. The long-term effects of normalized haematocrit/haemoglobin values in uraemic patients have not yet been evaluated exhaustively in prospective, randomized, multicentre studies. Epoetin treatment has been shown to induce lasting improvements in patients' sense of well-being, reduce fatigue, increase appetite and work capacity, and improve exercise tolerance, libido and work performance. Further studies are needed to demonstrate whether greater haemoglobin concentrations are associated with greater improvements in quality of life during epoetin treatment.
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PMID:What are the short-term and long-term consequences of anaemia in CRF patients? 1033 65

Renal anaemia is an independent risk factor for the development of left ventricular hypertrophy (LVH), heart failure and mortality. Studies show that partial correction of anaemia leads to partial regression of LVH. However, early initiation of anaemia therapy may be the optimal way to reduce cardiac morbidity and mortality. The Cardiovascular risk Reduction by Early Anemia Treatment with Epoetin Beta (CREATE) trial will investigate the effect of early anaemia correction on cardiovascular risk reduction in patients not yet on renal replacement therapy. The primary objectives of this open, randomized, multicentre trial are to investigate the effect of early anaemia correction on the change in left ventricular mass index after 1 year, and the time to first cardiovascular event. The trial comprises two treatment arms: early intervention where patients will receive epoetin beta when their haemoglobin (Hb) level is 11-12.5 g/dl and their target Hb will be 13-15 g/dl, and late intervention, where patients will receive epoetin beta once their Hb level is <10.5 g/dl and their target Hb will be 10.5-11.5 g/dl. The study will be event-driven with a continuous evaluation and an interim analysis once every year. The inclusion of 600 patients is based on assumption of a 15-20% event rate in the control group and that 200 events are needed to detect a reduction of about one-third. In conclusion, the CREATE trial will examine whether early anaemia treatment will prevent development of LVH, reduce cardiovascular morbidity and provide other benefits.
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PMID:The CREATE trial--building the evidence. 1136 44

Anemia occurs frequently in chronic heart failure (CHF) patients and is associated with increased morbidity and mortality risk. Clinical trials with recombinant human erythropoietin in patients with chronic kidney disease and concomitant structural heart disease have demonstrated beneficial effects on ventricular remodeling but variable effects on clinical outcome. Preliminary clinical trials in patients with CHF demonstrate that erythropoietin therapy is well-tolerated and associated with short-term clinical benefits. The optimum target hemoglobin, erythropoietin dosing regimen, and role of iron supplementation in patients with CHF are not known. Darbepoetin alfa is a glycosylated derivative of erythropoietin with a prolonged half-life that may allow less frequent dosing in CHF populations. Additional studies are needed to determine the safety and efficacy of long-term erythropoietic therapy in CHF patients.
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PMID:Treatment of anemia in patients with chronic heart failure. 1500 95

In patients with chronic heart failure (CHF), anemia is associated with more severe symptoms and worse prognosis. Erythropoiesis-stimulating proteins (ESPs) increase hemoglobin and may be of therapeutic benefit. We investigated the pharmacokinetics and pharmacodynamics of the long-acting ESP, darbepoetin alfa, administered on 2 occasions 1 month apart to 30 healthy subjects and 33 patients with symptomatic CHF and anemia (hemoglobin<or=12.5 g/dL) in 2 randomized, double-blind, placebo-controlled studies. Subcutaneous (SC) and intravenous administration of 0.75 microg/kg of darbepoetin alfa were compared in a crossover study. The second study compared 2.0, 3.0, and 5.0 microg/kg SC doses with placebo. Darbepoetin alfa (0.75 microg/kg SC) pharmacokinetics were similar in CHF patients and healthy subjects, with a mean (+/-SD) bioavailability of 29 (+/-11)% and 37 (+/-8)%, respectively. In anemic CHF patients, mean (+/-SD) increases in hemoglobin at 4 weeks after the second monthly dose of 2.0, 3.0, and 5.0 microg/kg (SC) of darbepoetin alfa were 2.3 (+/-0.6), 1.4 (+/-1.0), and 2.4 (+/-1.9) g/dL, respectively. Darbepoetin alfa 0.75 microg/kg (SC) given twice, 1 month apart, was insufficient to increase hemoglobin in this study. No severe, drug-related adverse events occurred. Darbepoetin alfa administered once monthly elevates and maintains the hemoglobin concentration in patients with CHF and anemia.
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PMID:Once-monthly administration of darbepoetin alfa for the treatment of patients with chronic heart failure and anemia: a pharmacokinetic and pharmacodynamic investigation. 1604 26

The combination of heart failure and chronic kidney disease (CKD) has received comparatively little attention in terms of clinical research versus investigations of each state individually. It has been known for over a decade that anemia, a cardinal feature of CKD, is associated with higher cardiovascular event rates in late-stage and end-stage renal disease. Although the biological mechanisms linking anemia, renal failure, and heart failure are incompletely understood, more prevalent anemia is consistent in patients with more severe heart failure and is associated with higher mortality rates. Impaired erythropoietin production and resistance to erythropoietin are major contributors to anemia in patients with heart failure. By targeting hemoglobin levels in anemic patients with CKD, through the use of recombinant erythropoietin (epoetin) therapy, it has been hoped that anemia, CKD, and heart failure outcomes can be improved. Darbepoetin alfa was engineered to contain more N-linked carbohydrate chains than erythropoietin, and has an approximately 3 times longer serum half-life. Several clinical trials have addressed the hypothesis that darbepoetin alfa can effectively treat renal anemia at dose frequencies of once per week, or less often, with positive outcomes.
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PMID:Myocardial disease, anemia, and erythrocyte-stimulating proteins in chronic kidney disease. 1634 Sep 36

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the American College of Cardiology 55th Annual Scientific Session held in March 2006. All reports should be considered as preliminary data, as analyses may change in the final publication. Darbepoetin alfa increased haemoglobin levels in heart failure patients and improved some aspects of quality of life compared to placebo. In the ASTEROID study rosuvastatin significantly reduced LDL-cholesterol levels and induced regression of atherosclerosis in patients with CAD. Rosuvastatin also produced a significant reduction in LDL-cholesterol levels in heart failure patients in the UNIVERSE study, but had no effect on left ventricular remodelling compared to placebo. The paediatric carvedilol study failed to show a benefit of carvedilol in children with heart failure. Ultrafiltration produced a greater weight and fluid loss than intravenous diuretics in heart failure patients with volume overload in the UNLOAD study but did not exert a greater improvement in breathlessness; however, ultrafiltration did reduce readmission rates. The ICELAND MI study showed that CMR imaging was more sensitive than ECG or clinical criteria for detecting myocardial infarction.
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PMID:Clinical trials update from the American College of Cardiology: Darbepoetin alfa, ASTEROID, UNIVERSE, paediatric carvedilol, UNLOAD and ICELAND. 1669 3

Anemia is increasingly recognized as a common, important and treatable condition in patients with congestive heart failure. Despite increasing knowledge of anemia, as well as its co-association with chronic renal disease, advanced New York Heart Association class and worse prognosis, there are very few evidence-based recommendations for treatment. The use of supplemental iron, especially intravenous forms, for the treatment of iron-deficiency anemia in heart failure patients is associated with improved symptoms, cardiac size and function, and possibly improved outcomes. However, many patients with heart failure suffer from anemia due to other causes, including renal failure (so-called cardiorenal syndrome), erythropoietin resistance, possible ACE inhibitor use and extracellular fluid expansion. The association between anemia and adequate iron stores has led to interest in the use of erythrocyte-stimulating agents, such as erythropoietin and darbepoetin. While early data are promising, recent evidence in non-heart failure trials has led to caution in their use and given way to anticipation of results of ongoing definitive randomized trials of this therapy, such as the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) and Reduction of Events with Darbepoetin-alpha in Heart Failure (RED-HF) studies.
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PMID:Recognition and treatment of anemia in the setting of heart failure due to systolic left ventricular dysfunction. 1824 74

An association between anaemia, poor functional status and, compared to non-anaemic patients, worse clinical status and a higher risk of hospitalisation and death has been consistently reported in chronic heart failure (CHF), although cause an effect has not been proven. While it is attractive to think that correction of a co-morbidity that exacerbates already diminished delivery of oxygen to the tissues in heart failure is likely to beneficial, the possible haemodynamic effects of increasing haemoglobin, for example vasoconstriction, might not be. Consequently, the balance of benefit and risk of anaemia correction in CHF is uncertain, may vary according to the severity of anaemia (and other factors) and needs to be properly evaluated. To date, most studies of anaemia correction in CHF have used erythropoiesis stimulating agents (ESAs). The trials with erythropoietin have been of small size, uncontrolled or unblended/single blind, raising concerns again about interpretation of subjective outcomes. In addition, the analyses of these trials have been suboptimal. Two double-blind, placebo-controlled, darbepoetin studies have been published in full. Neither showed an improvement in functional capacity or consistent effect on patient reported symptoms/quality of life. Darbepoetin is, however, currently being tested in a large-scale, phase III morbidity and mortality trial, the Reduction of Events with Darbepoetin alfa in Heart Failure (RED-HF) which should contribute important information of the safety and efficacy of ESAs in this syndrome. Other approaches, notably parenteral iron supplementation, are also being evaluated and other agents for anaemia correction are under development.
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PMID:Approaches to the treatment of anaemia in patients with chronic heart failure. 1839 91

Anemia is a common comorbidity in patients with heart failure and is associated with worse long-term outcomes. Although the cause of anemia in heart failure is unclear, the weight of evidence suggests that renal dysfunction, along with neurohormonal and proinflammatory cytokine activation in heart failure, favors the development of anemia of chronic disease, with defective iron utilization, inappropriate erythropoietin production, and depressed bone marrow function. Similarly, the mechanisms by which anemia worsens heart failure outcomes are unknown but may be related to increased myocardial workload. If anemia is a mediator and not just a marker of poor outcomes, correcting anemia could become an important and novel therapeutic target to improve long-term outcomes in such patients. Indeed, several small-sized studies have shown the beneficial effects of empirically treating anemia in heart failure patients with recombinant erythropoietin and intravenous iron. However, the ideal threshold at which therapy should be initiated and the extent of correction considered safe and desirable in the individual patient with heart failure need to be known. These issues become more important because of increasing safety concerns that recombinant erythropoietin therapy for treating anemia may be associated with adverse cardiovascular outcomes in patients with chronic kidney disease and may worsen cancer in patients receiving chemotherapy to treat various types of cancer. Therefore, further prospectively designed studies are required to address some of these questions. Fortunately, 2 large mortality morbidity trials, TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) in patients with chronic kidney disease and RED-HF (Reduction of Events with Darbepoetin alfa in Heart Failure) in heart failure patients, are in progress and are likely to provide definitive answers.
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PMID:Anemia and chronic heart failure implications and treatment options. 1868 41

Patients with chronic kidney disease (CKD) have a high burden of mortality and cardiovascular morbidity. Additional strategies to modulate cardiovascular risk in this population are needed. Anaemia has been associated with adverse outcomes in CKD populations, and the ability to modify this parameter with the use of erythropoiesis-stimulating agents has been a topic of much debate. Data on the effects of anaemia correction on cardiovascular outcomes and survival in CKD have been both discordant and controversial. It is hoped that the ongoing Trial to Reduce cardiovascular Events with Aranesp Therapy (TREAT) will help to redress the current clinical gaps and the uncertainty over the optimal management of anaemia in patients with CKD and type 2 diabetes mellitus. Anaemia is also increasingly being recognized as an important comorbid condition in patients with symptomatic heart failure. The ongoing Reduction of Events with Darbepoetin alfa in Heart Failure (RED-HF(TM)) trial is designed to determine whether the treatment of anaemia improves outcomes in such patients.
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PMID:Future perspectives on treatment with erythropoiesis-stimulating agents in high-risk patients. 1946 57


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