Effect of perindopril on physical function in elderly people with functional impairment: a randomized controlled trial

D. Sumukadas, M. D. Witham, A. D. Struthers, M. E.T. McMurdo
2007 CMAJ - Canadian Medical Association Journal  
A decline in physical function with age is strongly associated with disability in later life. Although regular exercise has been shown to increase muscle strength and to slow functional decline, the majority of elderly people are sedentary and either unwilling or simply unable to contemplate adequate exercise participation. Alternative strategies to improve physical function are required. Several strands of evidence suggest a possible role for angiotensin-converting-enzyme (ACE) inhibitors in
more » ... proving physical function in elderly people. First, ACE inhibitors improve endothelial function and may improve muscle function by increasing muscle blood flow and glucose delivery. 1 Second, an observational study involving elderly women with hypertension reported that ACE inhibitors slowed the decline in physical function and muscle strength when compared with other antihypertensive agents. 2 Third, people with the II genotype of the ACE gene have low ACE activity and have been found to have an enhanced endurance performance and an anabolic response to exercise training. 3 Fourth, use of an ACE inhibitor in a randomized placebo-controlled trial resulted in a significant improvement in exercise capacity among elderly patients with heart failure due to left ventricular systolic dysfunction. 4 Although this effect may have been the result of improved cardiac function, ACE inhibitors may have direct effects on skeletal muscle. We therefore sought to examine the effect of the ACE inhibitor perindopril on physical function in functionally impaired elderly people who had no heart failure or left ventricular systolic dysfunction. Methods Study design and participants This was a prospective, parallel-group, double-blind, randomized, placebo-controlled trial conducted between August 2003 and March 2006. Participants were recruited from among patients in the Medicine for the Elderly services in Tayside, Scotland, and from among patients attending other NHS services in Tayside. Patients aged 65 years or more with self-Background: Physical function and exercise capacity decline with age and are a major source of disability in older people. Recent evidence suggests a potential role for the reninangiotensin system in modulating muscle function. We sought to examine the effect of the angiotensin-convertingenzyme (ACE) inhibitor perindopril on physical function in elderly people with functional impairment who had no heart failure or left ventricular systolic dysfunction. Methods: In this double-blind randomized controlled trial, participants aged 65 years and older who had problems with mobility or functional impairment were randomly assigned to receive either perindopril or placebo for 20 weeks. The primary outcome was the change in the 6-minute walking distance over the 20 weeks. Secondary outcomes were changes in muscle function, daily activity levels, self-reported function and health-related quality of life. Results: A total of 130 participants were enrolled in the study (mean age 78.7, standard deviation 7.7 years); 95 completed the trial. At 20 weeks, the mean 6-minute walking distance was significantly improved in the perindopril group relative to the placebo group (mean between-group difference 31.4 m, 95% confidence interval [CI] 10.8 to 51.9 m; p = 0.003). There was a significant impact on health-related quality of life: although the mean score for part 1 of the EQ-5D questionnaire deteriorated over time in the placebo group, quality of life was maintained in the perindopril group, for a betweengroup difference of 0.09 (p = 0.046). There were no significant differences between the 2 groups in the other outcomes. Interpretation: Use of the ACE inhibitor perindopril improved exercise capacity in functionally impaired elderly people who had no heart failure and maintained healthrelated quality of life. The degree of improvement was equivalent to that reported after 6 months of exercise training. (International Standard Randomised Controlled Trial Register no. ISRCTN67679521). Abstract CMAJ 2007;177(8):867-74 From the Section of Ageing and Health (Sumukadas, Witham, McMurdo) and
doi:10.1503/cmaj.061339 pmid:17923654 pmcid:PMC1995143 fatcat:jpuryxxqu5f57n42o5mlnjsvm4