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      Efficacy and safety of nebivolol in elderly heart failure patients with impaired renal function: insights from the SENIORS trial

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          Abstract

          Aim

          To determine the safety and efficacy of nebivolol in elderly heart failure (HF) patients with renal dysfunction.

          Methods and results

          SENIORS recruited patients aged 70 years or older with symptomatic HF, irrespective of ejection fraction, and randomized them to nebivolol or placebo. Patients ( n = 2112) were divided by tertile of estimated glomerular filtration rate (eGFR). Mean age of patients was 76.1 years, 35% of patients had an ejection fraction of >35%, and 37% were women resulting in a unique cohort, far more representative of clinical practice than previous trials. eGFR was strongly associated with outcomes and nebivolol was similarly efficacious across eGFR tertiles. The primary outcome rate (all-cause mortality or cardiovascular hospital admission) and adjusted hazard ratio for nebivolol use in those with low eGFR was 40% and 0.84 (95% CI 0.67–1.07), 31% and 0.79 (0.60–1.04) in the middle tertile, and 29% and 0.86 (0.65–1.14) in the highest eGFR tertile. There was no interaction noted between renal function and the treatment effect ( P = 0.442). Nebivolol use in patients with moderate renal impairment (eGFR <60) was not associated with major safety concerns, apart from higher rates of drug-discontinuation due to bradycardia.

          Conclusion

          Nebivolol is safe and has a similar effect in elderly HF patients with mild or moderate renal impairment.

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          Most cited references37

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          ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM).

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            Renal function as a predictor of outcome in a broad spectrum of patients with heart failure.

            Decreased renal function has been found to be an independent risk factor for cardiovascular outcomes in patients with chronic heart failure (CHF) with markedly reduced left ventricular ejection fraction (LVEF). The aim of this analysis was to evaluate the prognostic importance of renal function in a broader spectrum of patients with CHF. The Candesartan in Heart Failure:Assessment of Reduction in Mortality and Morbidity (CHARM) program consisted of three component trials that enrolled patients with symptomatic CHF, based on use of ACE inhibitors and reduced ( 40%). Entry baseline creatinine was required to be below 3.0 mg/dL (265 micromol/L). Routine baseline serum creatinine assessments were done in 2680 North American patients. An analysis of the estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease equation and LVEF on risk of cardiovascular death or hospitalization for heart failure, as well as on all-cause mortality, was conducted on these 2680 patients. The proportion of patients with eGFR <60 mL/min per 1.73 m2 was 36.0%; 42.6% for CHARM-Alternative, 33.0% for CHARM-Added, and 34.7% for CHARM-Preserved. During the median follow-up of 34.4 months (total 6493 person-years), the primary outcome of cardiovascular death or hospital admission for worsening CHF occurred in 950 of 2680 subjects. Both reduced eGFR and lower LVEF were found to be significant independent predictors of worse outcome after adjustment for major confounding baseline clinical characteristics. The risk for cardiovascular death or hospitalization for worsening CHF as well as the risk for all-cause mortality increased significantly below an eGFR of 60 mL/min per 1.73 m2 (adjusted hazard ratio, 1.54 for 45 to 60 mL/min per 1.73 m2 and 1.86 for <45 mL/min per 1.73 m2 for the primary outcome, both P<0.001, and hazard ratio of 1.50, P=0.006, and 1.91, P=0.001, respectively, for all-cause mortality). The prognostic value of eGFR was not significantly different among the three component trials. There was no significant interaction between renal function, the effect of candesartan, and clinical outcome. Impaired renal function is independently associated with heightened risk for death, cardiovascular death, and hospitalization for heart failure in patients with CHF with both preserved as well as reduced LVEF. There was no evidence that the beneficial effect of candesartan was modified by baseline eGFR.
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              Anemia and mortality in heart failure patients a systematic review and meta-analysis.

              The aim of this study was to assess the effect of anemia on mortality in chronic heart failure (CHF). Anemia is frequently observed in patients with CHF, and evidence suggests that anemia might be associated with an increased mortality. A systematic literature search in MEDLINE (through November 2007) for English language articles was performed. In addition, a manual search was performed. We included cohort studies and retrospective secondary analyses of randomized controlled trials whose primary objective was to analyze the association between anemia and mortality in CHF. Of a total of 1,327 initial studies, we included 34 studies, comprising 153,180 patients. Information on study design, patient characteristics, outcome, and potential confounders were extracted. Anemia was defined by criteria used in the original articles. Of the 153,180 CHF patients, 37.2% were anemic. After a minimal follow-up of 6 months, 46.8% of anemic patients died compared with 29.5% of nonanemic patients. Crude mortality risk of anemia was odds ratio 1.96 (95% confidence interval: 1.74 to 2.21, p < 0.001). Lower baseline hemoglobin values were associated with increased crude mortality rates (r = -0.396, p = 0.025). Adjusted hazard ratios showed an increased adjusted risk for anemia (hazard ratio 1.46 [95% confidence interval: 1.26 to 1.69, p < 0.001]). Subgroup analysis showed no significant difference between mortality risk of anemia in diastolic or systolic CHF. Anemia is associated with an increased risk of mortality in both systolic and diastolic CHF. Anemia should, therefore, be considered as a useful prognosticator, and therapeutic strategies aimed to increase hemoglobin levels in CHF should be investigated.
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                Author and article information

                Contributors
                On behalf of : on behalf of the SENIORS Investigators
                Journal
                Eur J Heart Fail
                eurjhf
                eurjhf
                European Journal of Heart Failure
                Oxford University Press
                1388-9842
                1879-0844
                September 2009
                1 August 2009
                1 August 2009
                : 11
                : 9
                : 872-880
                Affiliations
                [1 ]Hôpital Lariboisiere, Assistance Publique-Hopitaux de Paris, simpleUniversité Paris Diderot, INSERM U942 , 2 Rue Ambroise Paré, 75475 Paris Cedex 10, France
                [2 ]simpleClinical Trials and Evaluation Unit, Royal Brompton Hospital , Sydney Street, London SW3 6NP, UK
                [3 ]National Heart and Lung Institute, simpleImperial College , London, UK
                [4 ]simpleUniversity Medical Center Groningen, University of Groningen , Groningen, The Netherlands
                [5 ]Klinik für Innere Medizin III, simpleUniversität des Saarlandes , Homburg/Saar, Germany
                [6 ]Faculty of Medicine, simpleUniversity of Sydney , Sydney, Australia
                [7 ]simpleGVM Hospitals of Care and Research , Cotignola, Italy
                Author notes
                [* ]Corresponding author. Tel: +44 207 351 8827, Fax: +44 207 351 8829, Email: d.kotecha@ 123456rbht.nhs.uk
                [†]

                In memoriam

                Article
                hfp104
                10.1093/eurjhf/hfp104
                2729679
                19648605
                f7df9523-f941-4162-b9ee-9a96e516c167
                Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

                The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

                History
                : 24 June 2009
                : 3 July 2009
                Categories
                Treatment

                Cardiovascular Medicine
                renal impairment,nebivolol,beta-blocker,heart failure
                Cardiovascular Medicine
                renal impairment, nebivolol, beta-blocker, heart failure

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