The effect of spironolactone on exercise capacity in functionally impaired older people without heart failure

Abstract

With a growing ageing population decline in physical function has become a major public health issue, as it is associated with disability in later life. Recent evidence suggests that blockade of the renin-angiotension-aldosterone system may have a role in improving physical function in older people.We hypothesised that inhibition of the renin-angiotensin-aldosterone system with spironolactone would improve physical function in older people without heart failure. In a double-blind, randomised controlled clinical trial 120 participants, aged >65 years with functional impairment were randomized to receive 25mg spironolactone or placebo for 20 weeks. The primary outcome was the change in six-minute walking distance over 20 weeks. Secondary outcomes were change in Timed-Get-Up and Go test, Incremental Shuttle Walk Test, measures of health related quality of life (EuroQol health questionnaire and Functional Limitation Profile) and measures of psychological state (Hospital Anxiety and Depression Scale). Outcomes measures were repeated at 10 and 20 weeks.Participant mean age was 75 years (SD 6), 65/120 (54%) were male. Only 8/120 participants (6.6%) dropped out (5 from the placebo group, 3 from the spironolactone group). Of the 112 participants who completed the study 95% (106/112) remained on medication at 20 weeks. There was no significant change in six minute walking distance at 20 weeks with a -3.2 (95% CI -28.9, 22.5) metres difference between the spironolactone group related to the placebo group (p=0.81). There was however a significant improvement in quality of life at 20 weeks (a secondary outcome) with a rise in EuroQol EQ-5D score of 0.10 (95% CI 0.03, 0.18) in the spironolactone group relative to the placebo group (p=<0.01). There were no significant changes between groups in the other secondary outcomes. This trial found that spironolactone was safe and well tolerated, but did not improve physical function in older people who did not have heart failure. Quality of life improved, but the biological plausibility and possible mechanisms for this require further study.

Date of Award	2011
Original language	English
Awarding Institution	University of Dundee
Sponsors	Chief Scientist Office
Supervisor	Marion McMurdo (Supervisor) & Allan Struthers (Supervisor)