Effects of Valsartan on Circulating Brain Natriuretic Peptide and Norepinephrine in Symptomatic Chronic Heart Failure

Abstract

Background-Brain natriuretic peptide (BNP) and norepinephrine (NE) are strongly related to severity of and are independent predictors of outcome in heart failure. The long-term effects of angiotensin receptor blockers on BNP and NE in heart failure patients are not known. Methods and Results-Both BNP and NE were measured in 4284 patients randomized to valsartan or placebo in the Valsartan Heart Failure Trial (Val-HeFT) at baseline and 4, 12, and 24 months after randomization. The effects of valsartan were tested by ANCOVA, controlling for baseline values and concomitant ACE inhibitors and/or ␤-blockers. BNP and NE concentrations were similar at baseline in the 2 groups and were decreased by valsartan starting at 4 months and up to 24 months. BNP increased over time in the placebo group. At the end point, least-squares mean (ϮSEM) BNP increased from baseline by 23Ϯ5 pg/mL in the placebo group (nϭ1979) but decreased by 21Ϯ5 pg/mL (nϭ1940) in the valsartan group (PϽ0.0001). NE increased by 41Ϯ6 pg/mL (nϭ1979) and 12Ϯ6 pg/mL (nϭ1941) for placebo and valsartan, respectively (Pϭ0.0003). Concomitant therapy with both ACE inhibitors and ␤-blockers significantly reduced the effect of valsartan on BNP but not on NE (P for interactionϭ0.0223 and 0.2289, respectively). Conclusions-In Val-HeFT, the largest neurohormone study in patients with symptomatic chronic heart failure, BNP and NE rose over time in the placebo group. Valsartan caused sustained reduction in BNP and attenuated the increase in NE over the course of the study. Key Words: heart failure Ⅲ angiotensin Ⅲ natriuretic peptides Ⅲ norepinephrine Ⅲ trials N eurohormone activation is characteristic of heart failure (HF), and the magnitude of elevation of circulating levels of norepinephrine (NE), brain natriuretic peptide (BNP), and other neurohormones is directly related to mortality and morbidity. [1][2][3][4] The influence of therapy on neurohormone levels has been less well studied, in part because, with few exceptions, 5-8 hormone assays have usually been conducted in only a subset of the population in trials. The Valsartan Heart Failure Trial (V-HeFT) II demonstrated that enalapril therapy was associated with a reduction in plasma NE levels compared with the isosorbide dinitrate/hydralazine-positive control group. 5 In V-HeFT III, felodipine produced a modest reduction in atrial natriuretic peptide levels compared with placebo. 9 In the RESOLVD Pilot trial, candesartan combined with enalapril therapy caused a sustained reduction of BNP of Ϸ30 pg/mL over a period of 43 weeks. 7 None of those trials, however, had an adequate size to examine the response to therapy in subgroups of the population.Val-HeFT tested the effect on morbidity and mortality of the angiotensin receptor blocker valsartan versus placebo in addition to standard HF therapy, which may have included an ACE inhibitor (ACEi) and/or a ␤-blocker (BB) in 5010 patients with symptomatic HF. 10,11 Valsartan had no effect on mortality, but it decreased the other primary end point of combined morbidity/mo...

ANALYSIS OF CHANGE IN NT-proBNP AFTER ANGIOTENSIN RECEPTOR BLOCKER (ARB) THERAPY IN PATIENT WITH HEART FAILURE

“…ARB can modulate neurohormon on RAA system, that result in decreasing NTproBNP level on valsartan vs enalapril show decrease 15% vs 13% after 12 months therapy (Lee et al 2011, Masson et al 2008, Kasama et al 2006, Latini et al 2002. In this study, we also have similar result as previous study, that NT-proBNP decrease significantly (p=0,003) after 2 months therapy.…”

N-Terminal–Pro-Brain Natriuretic Peptide Predicts Outcome After Hospital Discharge in Heart Failure Patients

“…[23][24][25][26] In ambulatory patients, there is now a considerable body of evidence showing that ACE inhibitors, angiotensin II receptor 1 antagonists, and spironolactone decrease BNP levels. 21,[23][24][25][26] The decrease of BNP in response to ␤-blockers is observed after 6 to 12 months of therapy. 27 A pilot study reported that HF therapy guided to decrease NT-proBNP levels is associated with improved prognosis compared with therapy according to clinical status.…”

“…21,22 Measurement of BNP 4 months apart in the Valsartan Heart Failure Trial (Val-HeFT) provided additional prognostic information. Patients with an increase in BNP levels Ͼ30% had an almost double mortality.…”

N-Terminal Pro–B-Type Natriuretic Peptide Variability in Stable Dialysis Patients

“…Several factors affect NT-proBNP concentrations, including extracellular volume (12), cardiac rhythm (13), myocardial ischemia (14,15), the dialysis prescription (16), and cardiac pharmacotherapy (17)(18)(19). These influences were assessed at every visit using a structured clinical interview, physical examination, and medical records review to ascertain interim hospitalization and changes to medication and/or the dialysis prescription.…”