TY - JOUR
T1 - Sustained reduction of aldosterone in response to the angiotensin receptor blocker Valsartan in patients with chronic heart failure
T2 - Results from the Valsartan heart failure trial
AU - Cohn, Jay N.
AU - Anand, Inder S.
AU - Latini, Roberto
AU - Masson, Serge
AU - Chiang, Yann Tong
AU - Glazer, Robert
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2003/9/16
Y1 - 2003/9/16
N2 - Background - Aldosterone has been implicated in the progression of heart failure. The Valsartan Heart Failure Trial (Val-HeFT) provided the first opportunity to examine the long-term effects of an angiotensin receptor blocker on plasma aldosterone levels in patients with NYHA class II through IV heart failure. Methods and Results - Plasma aldosterone was measured by radioimmunoassay in core laboratories at baseline and during follow-up in patients assigned to valsartan at a target dose of 160 mg twice daily or placebo. In the placebo group, aldosterone (baseline, 150±160 pg/mL, mean±SD; n = 2025) increased at 4, 12, and 24 months. In the valsartan group, aldosterone (baseline, 137±124 pg/mL, mean±SD; n = 2023) decreased at 4 months and remained suppressed for up to 2 years. At end point (last measurement in each patient), mean aldosterone increased by 17.8±3.0 pg/mL (SEM) (11.9%) in the placebo group and decreased by 23.8±3.0 pg/mL (SEM) (-17.4%) in the in the valsartan group (P<0.00001). The effect of valsartan was similar in all subgroups, including those receiving neither ACE inhibitors (ACE-I) nor β-blockers (BB) at baseline and those receiving concomitant ACE-I or BB. In contrast, outcome effects varied in the 4 subgroups, with a statistically significant reduction in the combined mortality/morbidity end point in those receiving neither neurohormonal inhibitor and an adverse trend in those treated with both drugs. Conclusions - Valsartan added to background therapy for heart failure produces sustained reduction in plasma aldosterone, consistent with the observed significant reduction in the combined mortality/morbidity end point. A similar reduction in all subgroups based on ACE-I or BB therapy, despite differing clinical outcomes in these subgroups, suggests that aldosterone plasma levels may not be a critical marker of the progression of heart failure.
AB - Background - Aldosterone has been implicated in the progression of heart failure. The Valsartan Heart Failure Trial (Val-HeFT) provided the first opportunity to examine the long-term effects of an angiotensin receptor blocker on plasma aldosterone levels in patients with NYHA class II through IV heart failure. Methods and Results - Plasma aldosterone was measured by radioimmunoassay in core laboratories at baseline and during follow-up in patients assigned to valsartan at a target dose of 160 mg twice daily or placebo. In the placebo group, aldosterone (baseline, 150±160 pg/mL, mean±SD; n = 2025) increased at 4, 12, and 24 months. In the valsartan group, aldosterone (baseline, 137±124 pg/mL, mean±SD; n = 2023) decreased at 4 months and remained suppressed for up to 2 years. At end point (last measurement in each patient), mean aldosterone increased by 17.8±3.0 pg/mL (SEM) (11.9%) in the placebo group and decreased by 23.8±3.0 pg/mL (SEM) (-17.4%) in the in the valsartan group (P<0.00001). The effect of valsartan was similar in all subgroups, including those receiving neither ACE inhibitors (ACE-I) nor β-blockers (BB) at baseline and those receiving concomitant ACE-I or BB. In contrast, outcome effects varied in the 4 subgroups, with a statistically significant reduction in the combined mortality/morbidity end point in those receiving neither neurohormonal inhibitor and an adverse trend in those treated with both drugs. Conclusions - Valsartan added to background therapy for heart failure produces sustained reduction in plasma aldosterone, consistent with the observed significant reduction in the combined mortality/morbidity end point. A similar reduction in all subgroups based on ACE-I or BB therapy, despite differing clinical outcomes in these subgroups, suggests that aldosterone plasma levels may not be a critical marker of the progression of heart failure.
KW - Angiotensin
KW - Heart failure
KW - Trials
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U2 - 10.1161/01.CIR.0000091234.45664.62
DO - 10.1161/01.CIR.0000091234.45664.62
M3 - Article
C2 - 12939207
AN - SCOPUS:0141595104
SN - 0009-7322
VL - 108
SP - 1306
EP - 1309
JO - Circulation
JF - Circulation
IS - 11
ER -