Spironolactone in atrial fibrillation with preserved cardiac fraction: the IMPRESS-AF trial

Eduard Shantsila, Farhan Shahid, Yongzhong Sun, Jon Deeks, Melanie Calvert, Fisher James P, Paulus Kirchhof, Paramjit Gill, Gregory Lip

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Background: Patients with permanent atrial fibrillation (AF) have poor outcomes, exercise capacity, and quality of life even on optimal anticoagulation. Based on mechanistic and observational data, we tested whether the mineralocorticoid receptor antagonist spironolactone can improve exercise capacity, E/e' ratio, and quality of life in patients with permanent AF and preserved ejection fraction. Methods and results: The double-blind, placebo-controlled IMPRESS-AF trial (NCT02673463) randomised 250 stable patients with permanent AF and preserved left ventricular ejection fraction to spironolactone 25 mg daily or placebo. Patients were followed for 2 years. The primary efficacy outcome was peak oxygen consumption (VO2peak) on cardiopulmonary exercise testing at 2 years. Secondary end points included 6-minute walk distance, E/e' ratio, quality of life, and hospital admissions. Spironolactone therapy did not improve VO2peak at 2 years (14.0 mL/min/kg [SD 5.4]) compared to placebo (14.5 [5.1], adjusted treatment effect (TE) -0.28, 95% confidence interval (CI) [-1.27, 0.71]; p=0.58). The findings were consistent across all sensitivity analyses. There were no differences in the 6-minute walking distance (TE -8.47 m [-31.9, 14.9]; p=0.48), E/e’ ratio (TE -0.68 [-1.52; 0.17], p=0.12), or quality of life (p=0.74 for Euroqol EQ-5D-5L and p=0.84 for MLWHF). At least one hospitalisation occurred in 15% of patients in spironolactone group and 23% in placebo group (p=0.15). Estimated glomerular filtration rate was reduced by 6 mL/min in spironolactone group with less than one-unit reduction in controls (p<0.001). Systolic BP was reduced by 7.2 mmHg (95% CI 2.2 to 12.3) in spironolactone group vs placebo (p=0.005). Conclusions: Spironolactone therapy does not improve exercise capacity, E/e' ratio, or quality of life in patients with chronic AF and preserved ejection fraction. Registration Information EudraCT number 2014-003702-33 and clinicaltrial.gov (NCT02673463). Key words: atrial fibrillation, heart failure, preserved ejection fraction, spironolactone, randomised clinical trial
Original languageEnglish
Pages (from-to)e016239
JournalJournal of the American Heart Association
Issue number18
Early online date10 Sept 2020
Publication statusPublished - 15 Sept 2020


  • Heart Failure
  • Randomised clinical trial
  • atrial fibrillation
  • preserved ejection fraction
  • spironolactone


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