Use of ACE inhibitor by patients with peripheral artery disease may improve pain-free walking

(Press-News.org) Among patients with peripheral artery disease and intermittent claudication (pain in the calf that comes and goes, typically felt while walking), 24 weeks of treatment with the angiotensin-converting enzyme (ACE) inhibitor ramipril was associated with improvement in pain-free and maximum walking times and the physical health aspect of quality of life, according to a study appearing in the February 6 issue of JAMA.

"Approximately 27 million individuals in Europe and North America have peripheral artery disease (PAD). Intermittent claudication occurs in approximately one-third of patients with PAD and typically presents as pain within leg muscle groups that occurs during walking but is relieved by rest. Patients with intermittent claudication have significant impairment in ambulatory function, resulting in functional disability and significant lifestyle limitation. Treatment of these patients is aimed at reducing cardiovascular risk, increasing functional performance, and improving health-related quality of life," according to background information in the article. Current drug treatments to improve walking distance have limited efficacy. A pilot trial with ramipril showed promising results. However, that trial was small and the findings were restricted to a subset of patients who comprise approximately one-half of all patients with claudication.

Anna A. Ahimastos, Ph.D., of the Baker IDI Heart and Diabetes Institute, Melbourne, Australia, and colleagues conducted a study to examine the association of ramipril therapy on walking distance and health-related quality of life as compared with placebo in a larger, more general PAD population. The randomized, placebo-controlled trial included 212 patients with peripheral artery disease (average age, 65.5 years), initiated in May 2008 and completed in August 2011. Patients were randomized to receive 10 mg/d of ramipril (n = 106) or matching placebo (n = 106) for 24 weeks. The primary outcome measures for the study were maximum and pain-free walking times, as recorded during a standard treadmill test. The Walking Impairment Questionnaire (WIQ) and Short-Form 36 Health Survey (SF-36) were used to assess walking ability and quality of life, respectively.

The researchers found that relative to placebo, ramipril was associated with a 75-second increase in average pain-free walking time and a 255-second increase in maximum walking time (a 77 percent and 123 percent increase in pain-free and maximum walking times, respectively). Compared to placebo, ramipril was also associated with improvements in WIQ scores (median distance, speed score and stair climbing) and the overall SF-36 median Physical Component Summary score.

"The increase in WIQ scores suggests that ramipril improves patient-perceived ability to perform normal daily activities. Ramipril therapy was also associated with moderate improvement in the physical health component of the SF-36 score. Importantly, these associations were additional to those achieved with standard clinical management by a general practitioner or vascular specialist. Further benefits may be achieved by adherence to lifestyle recommendations including smoking cessation and regular exercise, as well as more aggressive medical management of cardiovascular risk factors," the authors write.

"To our knowledge, this is the first adequately powered randomized trial demonstrating that treatment with ramipril is associated with improved treadmill walking performance in patients with PAD." (JAMA. 2013;309(5):453-460; Available pre-embargo to the media at http://media.jamanetwork.com)

Editor's Note: This study was supported by the National Heart Foundation of Australia, the National Health and Medical Research Council of Australia, and the Operational Infrastructure Support Program of the Victorian State Government, Australia. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Please Note: An author podcast on this study will be available post-embargo on the JAMA website.

Editorial: Medications for Improving Walking Performance in Peripheral Artery Disease - Still Miles to Go

Mary McGrae McDermott, M.D., of the Northwestern University Feinberg School of Medicine, Chicago, (also Contributing Editor, JAMA) comments on the results of this study in an accompanying editorial.

"A recent report from the Global Disease Burden study concluded that global disease burden continues to shift away from communicable to noncommunicable diseases and from premature death to greater years lived with disability. New therapies are needed to improve mobility and reduce disability among men and women living with PAD and other chronic diseases. Further study is needed to confirm the findings reported by Ahimastos et al and to determine whether ramipril therapy and other ACE inhibitors improve walking performance in ethnically diverse populations." (JAMA. 2013;309(5):487-488; Available pre-embargo to the media at http://media.jamanetwork.com)

Editor's Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. McDermott reported serving as a consultant for Ironwood Pharmaceuticals, a company that develops drugs used to treat peripheral artery disease (PAD), and serving as the medical editor for PAD for the Foundation for Informed Medical Decision Making.

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