Journal
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
Volume 65, Issue 11, Pages 2374-2382Publisher
WILEY
DOI: 10.1111/jgs.14940
Keywords
heart failure; exercise tolerance; aging; aldosterone antagonist; arterial function
Categories
Funding
- National Institutes of Health (NIH) [R01AG18915]
- Claude D. Pepper Older Americans Independence Center, Wake Forest University [P30AG21332]
- Clinical and Translational Science Institute, Wake Forest School of Medicine [NIH UL1TR001420]
- Kermit G. Phillips Chair in Cardiovascular Medicine of Wake Forest School of Medicine
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OBJECTIVES: To evaluate the effects of an aldosterone antagonist on exercise intolerance in older adults with heart failure and preserved ejection fraction (HFpEF). DESIGN: Randomized, placebo-controlled, double-blind trial. SETTING: Academic medical center, Winston-Salem, North Carolina. PARTICIPANTS: Older adults (N = 80, aged 71 +/- 1; 80% female) with stable compensated HFpEF and controlled blood pressure (BP). MEASUREMENTS: Participants were randomized into a 9-month treatment of spironolactone 25 mg/d vs placebo. Assessments were peak exercise oxygen consumption (VO2), 6-minute walk test, Minnesota Living with Heart Failure Questionnaire (MLHFQ), cardiac magnetic resonance imaging, Doppler echocardiography, and vascular ultrasound. RESULTS: Seventy-one participants completed the trial: 37 in the spironolactone group and 34 in the placebo group. Adherence according to pill count was excellent (spironolactone 95%, placebo 97%). Mean spironolactone dose was 24.3 +/- 2.9 mg/d and was well tolerated. Spironolactone significantly reduced systolic and diastolic BP at rest and peak exercise. At 9-month follow-up, baseline-adjusted peak VO2, the primary outcome, was 13.5 +/- 0.3 mL/kg per minute in the spironolactone group versus 13.9 +/- 0.3 mL/kg per minute in the placebo group (adjusted mean difference -0.4 mL/kg per minute; 95% confidence interval = -1.1-0.4 mL/kg per minute; P=.38). The 95% confidence intervals of spironolactone's effect on peak VO2 (-8.2% to 3.2%) excluded a clinically significant beneficial effect. There were also no significant differences in 6-minute walk distance, arterial stiffness, left ventricular (LV) mass, LV mass/end-diastolic volume, or MLHFQ score. CONCLUSION: In older adults with stable compensated HFpEF, 9 months of spironolactone 25 mg/d was well tolerated and reduced BP but did not improve exercise capacity, quality of life, LV mass, or arterial stiffness.
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