Patients with permanent atrial fibrillation have quality of life, exercise capacity, and poor outcomes even on optimal anticoagulation. Based on the observational and mechanistic data, we tested whether the mineralocorticoid receptor antagonist spironolactone can improve quality of life, E/e’ ratio, and exercise capacity in patients with permanent atrial fibrillation preserved ejection fraction.

The primary efficacy outcome was peak oxygen consumption on cardiopulmonary exercise testing at two years. Secondary endpoints included 6‐minute walk distance, E/e’ ratio, quality of life, and hospital admissions. Spironolactone therapy did not improve peak oxygen consumption at two years compared with placebo. There were no differences in the 6‐minute walking distance, E/e’ ratio, or quality of life. Estimated glomerular filtration rate was reduced by 6 mL/min in the spironolactone group with a less than 1‐unit reduction in controls. 7.2 mm Hg reduced systolic blood pressure in the spironolactone group versus placebo.

In conclusion, spironolactone therapy does not improve quality of life, E/e’ ratio, or exercise capacity in patients with preserved ejection fraction and chronic atrial fibrillation. Furthermore, spironolactone leads to worsening renal function, which should be considered in this patient population, and the use of mineralocorticoid receptor antagonists may mandate closer monitoring of renal function.