| Proteinuria, chronic kidney disease, and the effect of an angiotensin receptor blocker in addition to an angiotensin-converting enzyme inhibitor in patients with moderate to severe heart failure. | |
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MedLine Citation:
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PMID: 19805651 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Chronic kidney disease (CKD) is an established risk factor for poor outcomes in heart failure (HF). Whether proteinuria provides additional prognostic information is not known. Renin-angiotensin blockade medications improve outcomes in HF but are underutilized in HF patients with renal dysfunction because of safety concerns and a lack of evidence of their effectiveness. METHODS AND RESULTS: In the Valsartan in Heart Failure Trial (Val-HeFT), 5010 patients with class II, III, or IV heart failure were randomly assigned to receive valsartan or placebo. The 2 primary outcomes were death and first morbid event, defined as death, sudden death with resuscitation, hospitalization for HF, or administration of intravenous inotropic or vasodilator drugs for 4 hours or more without hospitalization. The study cohort was divided into subgroups according to the presence of CKD (estimated glomerular filtration rate <60 mL x min(-1) x 1.73 m(-2)) and proteinuria (positive dipstick). Multivariable Cox proportional hazards regression models were used to examine the relationships between study outcomes and proteinuria, including its interaction with CKD. The interaction between valsartan and CKD was also tested. The effect of valsartan on estimated glomerular filtration rate was estimated by generalized linear models, including tests of interactions between treatment and CKD. At baseline, CKD was found in 58% and dipstick-positive proteinuria in 8% of patients. Dipstick-positive proteinuria was independently associated with mortality (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.01 to 1.62, P=0.05) and first morbid event (HR 1.28, 95% CI 1.06 to 1.55, P=0.01). The increased risk of death associated with dipstick-positive proteinuria was similar for those with and without CKD (HR 1.26, 95% CI 0.96 to 1.66 versus HR 1.37, 95% CI 0.83 to 2.26; P=0.94), as was the hazard for first morbid event (HR 1.26, 95% CI 1.01 to 1.57 versus HR 1.42, 95% CI 0.98 to 2.07; P=0.71). Valsartan reduced estimated glomerular filtration rate compared with placebo to a similar extent (P=0.52) in the subgroups with CKD (mean reduction -3.6 mL x min(-1) x 1.73 m(-2)) and without CKD (mean reduction -4.0 mL x min(-1) x 1.73 m(-2)) and by -3.8 mL x min(-1) x 1.73 m(-2) in both groups combined. The beneficial effect of valsartan on first morbid events was similar in those with and without CKD (HR 0.86, 95% CI 0.74 to 0.99 versus HR 0.91, 95% CI 0.73 to 1.12; P=0.23) and was significant in the subgroup with CKD. The effect of valsartan on mortality did not differ in patients with and without CKD (HR 1.01, 95% CI 0.85 to 1.20 versus HR 0.91, 95% CI 0.69 to 1.25; P=0.08). CONCLUSIONS: CKD was common and dipstick-positive proteinuria was infrequent in this sample of patients with HF. After controlling for other risk factors, including CKD, the relatively small subgroup with dipstick-positive proteinuria did have worse outcomes. Valsartan reduced the estimated glomerular filtration rate by the same amount in patients with and without CKD and reduced the risk of the first morbid event in patients with CKD, which suggests its beneficial effects in patients with HF and CKD. |
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Authors:
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Inder S Anand; Kalkidan Bishu; Thomas S Rector; Areef Ishani; Michael A Kuskowski; Jay N Cohn |
Publication Detail:
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Type: Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2009-10-05 |
Journal Detail:
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Title: Circulation Volume: 120 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-10-20 Completed Date: 2009-11-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 1577-84 Citation Subset: AIM; IM |
Affiliation:
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VA Medical Center, Cardiology 111-C, Minneapolis, Minn 55417, USA. anand001@umn.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Angiotensin II Type 1 Receptor Blockers / adverse effects, therapeutic use* Angiotensin-Converting Enzyme Inhibitors / adverse effects, therapeutic use* Chronic Disease Double-Blind Method Drug Therapy, Combination Female Glomerular Filtration Rate / drug effects Heart Failure / complications*, drug therapy*, physiopathology Humans Kidney Diseases / complications*, physiopathology Male Middle Aged Proteinuria / complications* Severity of Illness Index Tetrazoles / adverse effects, therapeutic use* Treatment Outcome Valine / adverse effects, analogs & derivatives*, therapeutic use |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin II Type 1 Receptor Blockers; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Tetrazoles; 137862-53-4/valsartan; 7004-03-7/Valine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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