Bharathi Upadhya1, William G Hundley1, Peter H Brubaker2, Timothy M Morgan3, Kathryn P Stewart1, Dalane W Kitzman1. 1. Cardiovascular Medicine Section, Department of Internal Medicine, School of Medicine, Wake Forest University, Winston-Salem, North Carolina. 2. Department of Health and Exercise Science, Wake Forest University, Winston-Salem, North Carolina. 3. Division of Public Health Sciences, School of Medicine, Wake Forest University, Winston-Salem, North Carolina.
Abstract
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 thespironolactone 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.
RCT Entities:
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.
Authors: Theophilus E Owan; David O Hodge; Regina M Herges; Steven J Jacobsen; Veronique L Roger; Margaret M Redfield Journal: N Engl J Med Date: 2006-07-20 Impact factor: 91.245
Authors: Bishnu P Dhakal; Rajeev Malhotra; Ryan M Murphy; Paul P Pappagianopoulos; Aaron L Baggish; Rory B Weiner; Nicholas E Houstis; Aaron S Eisman; Stacyann S Hough; Gregory D Lewis Journal: Circ Heart Fail Date: 2014-10-24 Impact factor: 8.790
Authors: Dalane W Kitzman; Peter H Brubaker; Timothy M Morgan; Kathryn P Stewart; William C Little Journal: Circ Heart Fail Date: 2010-09-17 Impact factor: 8.790
Authors: Philip M Mottram; Brian Haluska; Rodel Leano; Diane Cowley; Michael Stowasser; Thomas H Marwick Journal: Circulation Date: 2004-07-26 Impact factor: 29.690
Authors: Dalane W Kitzman; Peter Brubaker; Timothy Morgan; Mark Haykowsky; Gregory Hundley; William E Kraus; Joel Eggebeen; Barbara J Nicklas Journal: JAMA Date: 2016-01-05 Impact factor: 56.272
Authors: Nicola C Edwards; Richard P Steeds; Paul M Stewart; Charles J Ferro; Jonathan N Townend Journal: J Am Coll Cardiol Date: 2009-08-04 Impact factor: 24.094
Authors: Enrico Vizzardi; Paolo Della Pina; Giorgio Caretta; Ivano Bonadei; Edoardo Sciatti; Carlo Lombardi; Antonio D'Aloia; Antonio Curnis; Marco Metra Journal: J Cardiovasc Med (Hagerstown) Date: 2015-09 Impact factor: 2.160
Authors: Gregory J Grosicki; Thomas G Travison; Hao Zhu; Jay Magaziner; Ellen F Binder; Marco Pahor; Rosaly Correa-de-Araujo; Peggy M Cawthon; Shalender Bhasin; Denise Orwig; Susan Greenspan; Todd Manini; Joe Massaro; Adam Santanasto; Sheena Patel; Roger A Fielding Journal: J Am Geriatr Soc Date: 2020-07-07 Impact factor: 5.562
Authors: Bharathi Upadhya; Nicholas M Pajewski; Michael V Rocco; W Gregory Hundley; Gerard Aurigemma; Craig A Hamilton; Jeffrey T Bates; Jiang He; Jing Chen; Michel Chonchol; Steve P Glasser; Adriana M Hung; Roberto Pisoni; Henry Punzi; Mark A Supiano; Robert Toto; Addison Taylor; Dalane W Kitzman Journal: Hypertension Date: 2021-03-29 Impact factor: 10.190
Authors: T Hauser; V Dornberger; U Malzahn; S J Grebe; D Liu; S Störk; M Nauck; N Friedrich; M Dörr; C Wanner; V Krane; F Hammer Journal: Int J Cardiovasc Imaging Date: 2021-02-05 Impact factor: 2.357