TY - JOUR
T1 - Spironolactone in atrial fibrillation with preserved cardiac fraction: the IMPRESS-AF trial
AU - Shantsila, Eduard
AU - Shahid, Farhan
AU - Sun, Yongzhong
AU - Deeks, Jon
AU - Calvert, Melanie
AU - James P, Fisher
AU - Kirchhof, Paulus
AU - Gill, Paramjit
AU - Lip, Gregory
PY - 2020/9/15
Y1 - 2020/9/15
N2 - 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
AB - 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
KW - Heart Failure
KW - Randomised clinical trial
KW - atrial fibrillation
KW - preserved ejection fraction
KW - spironolactone
UR - http://www.scopus.com/inward/record.url?scp=85091125435&partnerID=8YFLogxK
U2 - 10.1161/JAHA.119.016239
DO - 10.1161/JAHA.119.016239
M3 - Article
C2 - 32909497
SN - 2047-9980
VL - 9
SP - e016239
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 18
ER -