Do ACE Inhibitors Improve the Response to Exercise Training in Functionally Impaired Older Adults? A Randomized Controlled Trial

Abstract

Background.Loss of muscle mass and strength with ageing is a major cause for falls, disability, and morbidity in older people. Previous studies have found that angiotensin-converting enzyme inhibitors (ACEi) may improve physical function in older people. It is unclear whether ACEi provide additional benefit when added to a standard exercise training program. We examined the effects of ACEi therapy on physical function in older people undergoing exercise training.Methods.Community-dwelling people aged ≥65 years with functional impairment were recruited through general (family) practices. All participants received progressive exercise training. Participants were randomized to receive either 4 mg perindopril or matching placebo daily for 20 weeks. The primary outcome was between-group change in 6-minute walk distance from baseline to 20 weeks. Secondary outcomes included changes in Short Physical Performance Battery, handgrip and quadriceps strength, self-reported quality of life using the EQ-5D, and functional impairment measured using the Functional Limitations Profile.Results.A total of 170 participants (n = 86 perindopril, n = 84 placebo) were randomized. Mean age was 75.7 (standard deviation [SD] 6.8) years. Baseline 6-minute walk distance was 306 m (SD 99). Both groups increased their walk distance (by 29.6 m perindopril, 36.4 m placebo group) at 20 weeks, but there was no statistically significant treatment effect between groups (−8.6m [95% confidence interval: −30.1, 12.9], p = .43). No statistically significant treatment effects were observed between groups for the secondary outcomes. Adverse events leading to withdrawal were few (n = 0 perindopril, n = 4 placebo).Interpretation.ACE inhibitors did not enhance the effect of exercise training on physical function in functionally impaired older people.

Pharmacological Treatment and Current Management of Peripheral Artery Disease

“…At 20 weeks, both treatment groups increased their walking distance (29.6 m with perindopril versus 36.4 m with placebo, P=0.43). 131 Similarly, there was no difference between groups for the secondary outcomes of quality of life, functional impairment, or handgrip and quadricep strength. 131 A meta-analysis of ACEi therapy in patients with PAD and claudication included 6 randomized controlled trials, including 821 patients.…”

“…131 Similarly, there was no difference between groups for the secondary outcomes of quality of life, functional impairment, or handgrip and quadricep strength. 131 A meta-analysis of ACEi therapy in patients with PAD and claudication included 6 randomized controlled trials, including 821 patients. 132 Overall, there was an increase in maximum walking distance (mean differences 120.8 m, 95% CI 2.95-238.68, P=0.04), improved pain-free walking distance (P=0.003), but no change in ABI (P=0.11).…”

“…125 Another study, however, which selected patients with PAD over the age of 65, did not find benefit of ACEi therapy. 131 A total of 170 patients were randomized to either perindopril 4 mg daily or matching placebo and all received progressive exercise training. At 20 weeks, both treatment groups increased their walking distance (29.6 m with perindopril versus 36.4 m with placebo, P=0.43).…”

Living long and ageing well: is epigenomics the missing link between nature and nurture?

“…Drugs targeting the renin-angiotensin system (RAS) pathway, including angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs), have a long history of research reported to improve physical function (Simon et al 2015;Sumukadas et al 2014;Thornton and Norgren 2011;Burks et al 2011). Several studies have shown that ACE inhibitors improve exercise capacity in both younger and older people with heart failure (Hutcheon et al 2002), and in older fit subjects without apparent heart disease, a trial of ACE inhibitor showed a shift to type 1 muscle fibre type and increased exercise capacity (Sumukadas et al 2007).…”

Association Between Statin Use at Admission to Inpatient Rehabilitation and Functional Status at Discharge among Older Patients

“…30,31 However, in a recent randomized clinical trial, the use of ACE inhibitors did not increase the effect of exercise training, in particular endurance, in older patients with functional impairment. 32 Our findings of a positive association between ACE inhibitors and functional status might be due to the retrospective nature of the study with possible residual confounding but also to the different measure of functional outcome we have used. Indeed, we have evaluated the global functional status with the BI and not the patients' endurance with the 6-min walking test.…”