Effect of Spironolactone on Diastolic Function and Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction The Aldo-DHF Randomized Controlled Trial

2013 | journal article; research paper. A publication with affiliation to the University of Göttingen.

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​Effect of Spironolactone on Diastolic Function and Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction The Aldo-DHF Randomized Controlled Trial​
Edelmann, F. ; Wachter, R. ; Schmidt, A. G.; Kraigher-Krainer, E.; Colantonio, C.; Kamke, W. & Duvinage, A. et al.​ (2013) 
JAMA309(8) pp. 781​-791​.​ DOI: https://doi.org/10.1001/jama.2013.905 

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Authors
Edelmann, Frank ; Wachter, Rolf ; Schmidt, Albrecht G.; Kraigher-Krainer, Elisabeth; Colantonio, Caterina; Kamke, Wolfram; Duvinage, Andre; Stahrenberg, Raoul; Durstewitz, Kathleen; Loeffler, Markus; Duengen, Hans-Dirk; Tschoepe, Carsten; Herrmann-Lingen, Christoph ; Halle, Martin; Hasenfuß, Gerd ; Gelbrich, Götz; Pieske, Burkert 
Abstract
Importance Diastolic heart failure (ie, heart failure with preserved ejection fraction) is a common condition without established therapy, and aldosterone stimulation may contribute to its progression. Objective To assess the efficacy and safety of long-term aldosterone receptor blockade in heart failure with preserved ejection fraction. The primary objective was to determine whether spironolactone is superior to placebo in improving diastolic function and maximal exercise capacity in patients with heart failure with preserved ejection fraction. Design and Setting The Aldo-DHF trial, a multicenter, prospective, randomized, double-blind, placebo-controlled trial conducted between March 2007 and April 2012 at 10 sites in Germany and Austria that included 422 ambulatory patients (mean age, 67 [SD, 8] years; 52% female) with chronic New York Heart Association class II or III heart failure, preserved left ventricular ejection fraction of 50% or greater, and evidence of diastolic dysfunction. Intervention Patients were randomly assigned to receive 25 mg of spironolactone once daily (n=213) or matching placebo (n=209) with 12 months of follow-up. Main Outcome Measures The equally ranked co-primary end points were changes in diastolic function (E/e') on echocardiography and maximal exercise capacity (peak (V)over dotO(2)) on cardiopulmonary exercise testing, both measured at 12 months. Results Diastolic function (E/e') decreased from 12.7 (SD, 3.6) to 12.1 (SD, 3.7) with spironolactone and increased from 12.8 (SD, 4.4) to 13.6 (SD, 4.3) with placebo (adjusted mean difference, -1.5; 95% CI, -2.0 to -0.9; P<.001). Peak (V)over dotO(2) did not significantly change with spironolactone vs placebo (from 16.3 [SD, 3.6] mL/min/kg to 16.8 [SD, 4.6] mL/min/kg and from 16.4 [SD, 3.5] mL/min/kg to 16.9 [SD, 4.4] mL/min/kg, respectively; adjusted mean difference, +0.1 mL/min/kg; 95% CI, -0.6 to +0.8 mL/min/kg; P=.81). Spironolactone induced reverse remodeling (left ventricular mass index declined; difference, -6 g/m(2); 95% CI, -10 to -1 g/m(2); P=.009) and improved neuroendocrine activation (N-terminal pro-brain-type natriuretic peptide geometric mean ratio, 0.86; 95% CI, 0.75-0.99; P=.03) but did not improve heart failure symptoms or quality of life and slightly reduced 6-minute walking distance (-15m; 95% CI, -27 to -2m; P=.03). Spironolactone also modestly increased serum potassium levels (+0.2 mmol/L; 95% CI, +0.1 to +0.3; P<.001) and decreased estimated glomerular filtration rate (-5 mL/min/1.73m(2); 95% CI, -8 to -3 mL/min/1.73 m(2); P<.001) without affecting hospitalizations. Conclusions and Relevance In this randomized controlled trial, long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patients with heart failure with preserved ejection fraction. Whether the improved left ventricular function observed in the Aldo-DHF trial is of clinical significance requires further investigation in larger populations.
Issue Date
2013
Publisher
Amer Medical Assoc
Journal
JAMA 
ISSN
0098-7484
eISSN
1538-3598

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