on August 25, 2003
Published online before print August 25, 2003, doi: 10.1161/01.CIR.0000091234.45664.62
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© American Heart Association, Inc.
Clinical Investigation and Reports |
Sustained Reduction of Aldosterone in Response to the Angiotensin Receptor Blocker Valsartan in Patients With Chronic Heart Failure
Results From the Valsartan Heart Failure Trial
From the Cardiovascular Division (J.N.C.), Department of Medicine, University of Minnesota Medical School, Minneapolis, Minn; VA Medical Center (I.S.A.), Minneapolis, Minn; Istituto "Mario Negri" (R.L., S.M.), Milan, Italy; and Novartis Pharmaceuticals Corporation (Y.-T.C., R.G.), East Hanover, NJ.
Correspondence to Jay N. Cohn, MD, Cardiovascular Division, Mayo Mail Code 508, University of Minnesota Medical School, 420 Delaware St SE, Minneapolis, MN 55455. E-mail cohnx001{at}umn.edu
Received May 29, 2003; de novo received July 8, 2003; accepted July 28, 2003.
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 valsartan group (P<0.00001). The effect of valsartan was similar in all subgroups, including those receiving neither ACE inhibitors (ACE-I) nor ß-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.
Key Words: heart failure • angiotensin • trials
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