Summary Background Increased excretion of albumin in urine might be a marker of the various pathophysiological changes that arise in patients with heart failure. Therefore our aim was to assess the ...prevalence and prognostic value of a spot urinary albumin to creatinine ratio (UACR) in patients with heart failure. Methods UACR was measured at baseline and during follow-up of 2310 patients in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) Programme. The prevalence of microalbuminuria and macroalbuminuria, and the predictive value of UACR for the primary composite outcome of each CHARM study—ie, death from cardiovascular causes or admission to hospital with worsening heart failure—and death from any cause were assessed. Findings 1349 (58%) patients had a normal UACR, 704 (30%) had microalbuminuria, and 257 (11%) had macroalbuminuria. The prevalence of increased UACR was similar in patients with reduced and preserved left ventricular ejection fractions. Patients with an increased UACR were older, had more cardiovascular comorbidity, worse renal function, and a higher prevalence of diabetes mellitus than did those with normoalbuminuria. However, a high prevalence of increased UACR was still noted among patients without diabetes, hypertension, or renal dysfunction. Elevated UACR was associated with increased risk of the composite outcome and death even after adjustment for other prognostic variables including renal function, diabetes, and haemoglobin A1c . The adjusted hazard ratio (HR) for the composite outcome in patients with microalbuminuria versus normoalbuminuria was 1·43 (95% CI 1·21–1·69; p<0·0001) and for macroalbuminuria versus normoalbuminuria was 1·75 (1·39–2·20; p<0·0001). The adjusted values for death were 1·62 (1·32–1·99; p<0·0001) for microalbuminuria versus normoalbuminuria, and 1·76 (1·32–2·35; p=0·0001) for macroalbuminuria versus normoalbuminuria. Treatment with candesartan did not reduce or prevent the development of excessive excretion of urinary albumin. Interpretation Increased UACR is a powerful and independent predictor of prognosis in heart failure. Funding AstraZeneca.
Incidence and Predictors of Hyperkalemia in Patients With Heart Failure: An Analysis of the CHARM Program Akshay S. Desai, Karl Swedberg, John J. V. McMurray, Christopher B. Granger, Salim Yusuf, ...James B. Young, Mark E. Dunlap, Scott D. Solomon, James W. Hainer, Bertil Olofsson, Eric L. Michelson, Marc A. Pfeffer We examined the incidence and predictors of hyperkalemia in a broad population of patients with symptomatic heart failure enrolled in the CHARM (Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity) Program. Independent of assignment to candesartan or placebo, the risk of hyperkalemia increased with advanced age, male gender, baseline hyperkalemia, renal failure, diabetes, and background use of angiotensin-converting enzyme inhibitors or spironolactone. Candesartan increased the observed rate of hyperkalemia in these subgroups but was associated with a consistent reduction in the risk of cardiovascular death or heart failure hospitalization. Although renin-angiotensin-aldosterone antagonists improve clinical outcomes in heart failure patients, careful surveillance of serum potassium and creatinine is essential.
Objectives This study sought to investigate the efficacy and tolerability of candesartan, according to baseline blood pressure (BP), in the 4,576 patients with a low ejection fraction (EF) (≤0.40) in ...the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) program. Background Hypotension is a predictor of poor prognosis in heart failure, yet many treatments shown to reduce morbidity and mortality lower blood pressure. This paradox creates a dilemma for physicians and may explain why low BP is reported as a reason for under-use of these agents. Methods The interaction between treatment and baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) was examined with patients divided into 6 SBP categories (≤100, 101 to 110, 111 to 120, 121 to 130, 131 to 140 and ≥141 mm Hg) and 4 DBP categories (≤60, 61 to 70, 71 to 80 and ≥81 mm Hg). Results Low SBP and DBP were associated with worse clinical outcomes. Baseline BP did not modify the effects of candesartan on clinical outcomes: the interaction p value between SBP category and treatment was 0.38 (0.22 for DBP category). For both placebo and candesartan, study drug discontinuation for adverse effects (especially hypotension) was highest in patients in the lowest baseline BP categories. However, the relative risk of discontinuation for hypotension, renal dysfunction, and hyperkalemia in the candesartan compared with placebo group was not increased in patients with a low baseline BP. Conclusions In patients with low EF heart failure, the relative risks and benefits of candesartan treatment were similar in patients with a low BP compared to those with a higher BP.
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