A Novel Benefit of ACE Inhibitors in Functionally Impaired Older Adults

What can be done to help preserve physical function in elderly persons who are unable or unwilling to exercise?

When angiotensin-converting enzyme (ACE) inhibitors were first discovered, they were a welcome addition to the antihypertensive armamentarium. Since then, many more benefits of these drugs have been found: they slow the progression of diabetic nephropathy, abate the sequelae of heart failure when systolic dysfunction is present, and reduce the level of proteinuria in patients with nephrotic syndrome. A recent study provides preliminary support for another benefit of ACE inhibitors, specifically in functionally impaired older adults.¹

STUDY SHOWS SIGNIFICANT INCREASE IN WALKING DISTANCE

In an earlier study, it was observed that in elderly patients treated for hypertension with an ACE inhibitor, declines in physical strength were slowed-an effect that was not seen in those treated with other classes of antihypertensives.² Another study found that ACE inhibitors improve exercise tolerance in elderly persons with heart failure.³

Sumukadas and colleagues¹ hypothesized that ACE inhibitors may improve physical function in older adults by enhancing endothelial function and increasing glucose uptake by muscles. They conducted a prospective, parallel-group, double-blind, randomized, placebo-controlled study that enrolled 130 patients older than 65 years, without heart failure or systolic dysfunction, who had self-reported mobility problems or declining ability to perform activities of daily living; 95 of these patients completed the trial. Participants were randomized to perindopril (2 to 4 mg/d by titration) or placebo, and the trial was 20 weeks in duration. The primary outcome measure was a change in 6-minute walking distance.

At 20 weeks, the 6-minute walking distance was significantly increased in the perindopril group (mean group difference was 31.4 meters). This increase is equivalent to that produced by 6 months of exercise training. The difficulty of sustaining 6 months of supervised exercise in older adults makes these data even more impressive. In addition, health-related quality of life was preserved among those who received perindopril, and there was no increase in falls in this group.

A FEW CAVEATS ABOUT THE RESULTS

These are preliminary data. ACE inhibitor therapy can worsen hypotension-postural or otherwise-in elderly persons, which can result in dangerous falls. The careful scrutiny of potential participants before enrollment was responsible for the absence of falls in the active arm of the study. Only 24% of those screened met the enrollment criteria. Also, the usual adverse effects of ACE inhibitor therapy-elevated potassium and creatinine levels-were found in participants who received perindopril.

It appears that the list of potential benefits of ACE inhibitors continues to increase. Although a general recommendation for use in frail, elderly persons cannot be made as of yet, these results appear promising.

References:

REFERENCES:

1.

Sumukadas D, Witham MD, Struthers AD, McMurdo ME. Effect of perindopril on physical function in elderly people with functional impairment: a randomized controlled trial.

CMAJ.

2007;177:867-874.

2.

Onder G, Penninx BW, Balkrishnan R, et al. Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: an observational study.

Lancet

. 2002;359:926-930.

3.

Hutcheon SD, Gillespie ND, Crombie IK, et al. Perindopril improves six minute walking distance in older patients with left ventricular systolic dysfunction: a randomised double-blind placebo-controlled trial.

Heart

. 2002;88:373-377.