Sustained Reduction of Aldosterone in Response to the Angiotensin Receptor Blocker Valsartan in Patients With Chronic Heart Failure

<jats:p> <jats:bold> <jats:italic>Background—</jats:italic> </jats:bold> 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. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> 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 valsartan group ( <jats:italic>P</jats:italic> <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. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> 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. </jats:p>