Perindopril Comes Up Aces in Mobility Study

DUNDEE, Scotland, Oct. 8 -- A five-month course of the ACE inhibitor perindopril (Aceon) was equivalent to six months of exercise training for elderly patients with mobility problems, researchers here found.

In a randomized, double-blind, placebo-controlled trial, patients taking the drug saw their ability on the standard six-minute walk test increase significantly (P=0.003), according to Deepa Sumukadas, M.D., of the University of Dundee, and colleagues.

Also, those taking the drug maintained their quality of life while those getting placebo recorded a decline, Dr. Sumukadas and colleagues reported in the Oct. 9 issue of the Canadian Medical Association Journal.

"The degree of improvement was equivalent to that reported after six months of exercise training," the researchers said.

Although exercise training has been shown to improve function and quality of life for older patients, Dr. Sumukadas and colleagues said, many find themselves unable or unwilling to begin such a program.

There's evidence that ACE inhibitors can improve mobility and quality of life for older patients, especially those with heart failure from left-ventricular systolic dysfunction, Dr. Sumukadas and colleagues noted.

To see whether such drugs might help a broader population, the researchers enrolled 130 people with a mean age of 78.7 years and no heart failure or left-ventricular systolic dysfunction.

All had self-reported problems with mobility.

They were randomized to placebo or to 2 mg a day of perindopril. The drug dose was increased to 4 mg a day after two weeks if it was tolerated.

The primary outcome measure was improvement on the six-minute walk test, but the researchers also looked at other measures of physical function, as well as changes over the study on the EuroQol EQ-5D quality of life questionnaire.

After 20 weeks, the researchers found:

• Perindopril patients had improved their walking distance while placebo patients had declined slightly. The average difference between the groups on the six-minute walk test was significant at 31.4 meters.
• Most secondary outcome measures - such as the time needed to stand, walk three meters, and sit down again - did not change significantly.
• The exception was the first part of the quality-of-life questionnaire, which improved slightly for perindopril patients while falling for those on placebo. The average difference between the groups was 0.09 points on a scale ranging from minus 0.59 to 1.0, which was significant at P=0.046.

There has been concern that ACE inhibitors might lead to an increase in falls, but the difference between the groups in this study was not significant.

The researchers said more research with longer follow-up is needed. But in the meantime, doctors considering ACE inhibitors for other indications might also consider the "beneficial effects on exercise capacity and quality of life observed in this study," they said.

"Their results are promising and lend support to the hypothesis that ACE inhibition has a positive effect on physical function, possibly through effects on skeletal muscle," commented Ann Cranney, M.D., of the Ottawa Health Research Institute in Ottawa, Ontario, in an accompanying commentary.

Dr. Cranney drew attention to the difficulty of recruiting older patients, noting that only 24% of those screened for the trial met the eligibility criteria. In particular, she said, those with symptomatic hypotension were excluded, which "has implications for the applicability of these results to clinical practice."

Dr. Cranney agreed that larger trials are needed, and added that a focus should be to determine the mechanism involved in the improved function.