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Edelmann F, Wachter R, Schmidt AG, et al. Effect of Spironolactone on Diastolic Function and Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction: The Aldo-DHF Randomized Controlled Trial. JAMA. 2013;309(8):781–791. doi:10.1001/jama.2013.905
Author Affiliations: Department of Cardiology and Pneumology, Heart Center (Drs Edelmann, Wachter, Duvinage, Stahrenberg, Durstewitz, and Hasenfuss), German Center for Cardiovascular Research (Drs Edelmann, Wachter, Herrmann-Lingen, and Hasenfuss), and Department of Psychosomatic Medicine and Psychotherapy (Dr Herrmann-Lingen), University of Göttingen, Göttingen, Germany; Department of Cardiology, Medical University Graz (Drs Schmidt, Kraigher-Krainer, Colantonio, and Pieske) and Ludwig- Boltzmann Institute for Translational Heart Failure Research (Drs Kraigher-Krainer and Pieske), Graz, Austria; Department of Internal Medicine, MediClin Rehabilitation Center Spreewald, Spreewald, Germany (Dr Kamke); Institute of Medical Informatics, Statistics, and Epidemiology (Dr Löffler) and Clinical Trial Center, University of Leipzig (Dr Gelbrich), Leipzig, Germany; Department of Internal Medicine–Cardiology, Charité–Campus Virchow-Klinikum (Dr Düngen), and Department of Cardiology and Pneumology, Charité–Campus Benjamin Franklin, Universitätsmedizin (Dr Tschöpe), Berlin, Berlin, Germany; Department of Preventive and Rehabilitative Sports Medicine, Technical University Munich, Munich, Germany (Dr Halle); and Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany (Dr Gelbrich).
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 VO2) 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 VO2 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/m2; 95% CI, −10 to−1 g/m2; 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 (–15 m; 95% CI, –27 to –2 m; 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/1.73 m2; 95% CI, −8 to −3 mL/min/1.73 m2; 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.
Trial Registration clinicaltrials.gov Identifier: ISRCTN94726526; Eudra-CT No: 2006-002605-31
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