4.6 Article

Effect of Spironolactone on Exercise Tolerance and Arterial Function in Older Adults with Heart Failure with Preserved Ejection Fraction

Journal

JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
Volume 65, Issue 11, Pages 2374-2382

Publisher

WILEY
DOI: 10.1111/jgs.14940

Keywords

heart failure; exercise tolerance; aging; aldosterone antagonist; arterial function

Funding

  1. National Institutes of Health (NIH) [R01AG18915]
  2. Claude D. Pepper Older Americans Independence Center, Wake Forest University [P30AG21332]
  3. Clinical and Translational Science Institute, Wake Forest School of Medicine [NIH UL1TR001420]
  4. 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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