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CHARM: Renal dysfunction ups mortality/morbidity across spectrum of HF patients

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Impaired renal function raises the risk of cardiovascular mortality, all-cause mortality, and morbidity in CHF patients regardless of left-ventricular-ejection-fraction (LVEF) status, a new study, published in the February 7, 2006 issue of Circulation, has found

An analysis from the previously published Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program [2] shows an estimated glomerular filtration rate (eGFR) of <60 mL/min per 1.73m2 was independently associated with the study's primary outcomes of cardiovascular death and hospitalization due to worsening heart failure."Notably, decreased kidney function was an important predictor of worse outcomes in patients with relatively normal LVEF," said lead author Dr Hans Hillege (University Medical Center Groningen, the Netherlands) in a statement from the American Heart Association (AHA). "The patients with the worst kidney function had the highest risk of cardiovascular complications-with the risk being almost twice as high as in patients with normal kidney function." CHARM study coinvestigator Dr Marc Pfeffer (Brigham and Women's Hospital, Harvard Medical School, Boston, MA) added that this study should spur physicians on to strive for new ways to prevent worsening kidney function in all heart-failure patients regardless of LVEF status. Lower eGFR equals worse outcome In the AHA press statement, Pfeffer pointed out that previous research by his group and others has shown that impaired renal function worsens the prognosis in CHF patients with reduced LVEF. However, he said, until now it has not been clear whether this applies to CHF patients with relatively well-preserved LVEF.The initial CHARM study assessed the effect of candesartan (Atacand, AstraZeneca) in three distinct CHF populations- those with LVEF >40%, those with LVEF <40% and treated with an ACE inhibitor, and those with an LVEF of <40% and not treated with an ACE inhibitor due to previous intolerance. Baseline renal-function data in this cohort of 2680 North American patients were derived from subjects who had baseline serum creatinine assessments done to determine eligibility in the CHARM study. During an average three-year follow-up, 950 patients had a cardiovascular death or were hospitalized for worsening CHF. There were 650 all-cause deaths. The researchers report that both reduced eGFR and lower LVEF were significant, independent predictors of worse outcome after adjustment for major confounding baseline clinical characteristics, including diabetes, MI, stroke, previous hospitalizations for CHF, atrial fibrillation, and angina pectoris.According to the authors, there was a "stepwise increase in the cumulative incidence of CV death or admission to the hospital for heart failure across successively lower quintiles of eGFR." Further, they note, the most marked differences were seen in patients with an eGFR below 60 mL/min per 1.73m2."Click here to view a table on adjusted risk of cardiovascular death or hospitalization due to worsening CHF according to eGFR. “The risk from renal insufficiency persists even after adjustment for all other known covariates, including LVEF,” the authors write “Moreover, no evidence for interaction was observed among renal function, treatment allocation, and primary outcome.”The researchers recommend that future research focus on clarifying the link between reduced renal function and heart failure and developing new treatments to prevent or reverse the loss of kidney function in heart-failure patients.(Sources:(1) Hillege, HL, Nitsch D, Pfeffer MA, et al. Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation 2006; 113:671-678. (2) Pfeffer MA, Swedberg K, Granger CB, et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003; 362:759-766. The Heart: February 2006.)

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Posted On: 28 February, 2006
Modified On: 16 January, 2014

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