DynaMed EBM Focus 8 - Ramipril Improves Walking Ability in Selected Patients with Stable PAD and Intermittent Claudication

Last week 476 articles were evaluated via DynaMed's Systematic Literature Surveillance and 250 were added to DynaMed content.

Based on criteria for selecting "articles most likely to change clinical practice," one article of significant interest was selected by the DynaMed Editorial Team.

Ramipril Improves Walking Ability in Selected Patients with Stable PAD and Intermittent Claudication

About a third of patients with peripheral arterial disease (PAD) suffer from intermittent claudication that is relieved with rest. Cilostazol has been recommended by the American College of Cardiology/American Heart Association (J Am Coll Cardiol 2006 Mar 21;47(6):1239) for patients with PAD and claudication, but cilostazol and pentoxifylline, the only FDA-approved drugs for claudication, are each associated with relatively small improvements in walking performance (Cochrane Database Syst Rev 2008 Jan 23;(1):CD003748, Cochrane Database Syst Rev 2012 Jan 18;(1):CD005262, Br J Surg 2012 Dec;99(12):1630). A recent systematic review of small randomized trials assessing ACE inhibitors as a class found no overall improvements in walking (Int J Surg 2011;9(3):209). However, one of the included trials with 40 patients did show a benefit with the ACE inhibitor ramipril. Now, new a larger trial of ramipril provides strong evidence for its efficacy for claudication.

A total of 212 patients (mean age 66 years, 83% men) with stable PAD and intermittent claudication were randomized to ramipril 10 mg/day orally vs. placebo for 24 weeks. All patients were on a stable drug regimen for at least 6 months prior to randomization (55% taking antiplatelet agents, 55% taking statins, 9.4% taking cilostazol). The list of exclusion criteria was long, and included blood pressure ≥ 160/100 mmHg, use of ACE inhibitors or ARBs within 6 months, and any condition other than PAD that limited walking. Quality of life was assessed using the SF-36. Walking performance was assessed at baseline and at 6-months by a treadmill test (3.2 km/hour [2 miles/hour] and 12% grade). At baseline, the mean pain-free walking times were 140 seconds for the ramipril group and 144 seconds for the placebo group. The mean maximum walking times were 234 seconds (ramipril) and 238 seconds (placebo).

At 6 months, the pain-free walking time was increased by mean 88 seconds with ramipril vs. mean 14 seconds with placebo (p < 0.001), corresponding to an increased walking distance of 184 meters with ramipril (level 1 [likely reliable] evidence). Maximum walking times were increased by mean 277 seconds vs. 23 seconds (p < 0.001). Ramipril was also associated with improvements in patient-reported walking distance, walking speed, and stair climbing (p < 0.001 for each), and in quality of life on the physical component of the SF-36 (p = 0.02) (JAMA 2013 Feb 6;309(5):453). Whether these findings can be generalized to a larger PAD population, including patients with a greater degree of hypertension, or with comorbidities that also limit walking are questions for further study.

For more information, see the Peripheral arterial disease (PAD) of lower extremities topic in DynaMed.

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Quick Links Previous EBM Focus Issues Become a DynaMed Reviewer DynaMed Free Trial Send Comment to Editor Credits Physicians: .25 AMA PRA Category ICredits^TM Family Physicians: .25 Prescribed credits Nurse Practitioners: .25 Contact hours Release Date: February 13, 2013 Expiration Date: February 13, 2014 Estimated Completion Time: 15 minutes There is no fee for this activity. To Receive Credit In order to receive your certificate of participation, you should read the information about this activity, including the disclosure statements, review the entire activity, take the post-test, and complete the evaluation form. You may then follow the directions to print your certificate of participation. To begin, click the CME icon at the end of the article. Program Overview Learning Objectives Upon successful completion of this educational program, the reader should be able to: 1. Discuss the significance of this article as it relates to your clinical practice. 2. Be able to apply this knowledge to your patient's diagnosis, treatment and management. Faculty Information Alan Ehrlich, MD - Assistant Clinical Professor in Family Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; Senior Deputy Editor, DynaMed, Ipswich, Massachusetts, USA Michael Fleming, MD, FAAFP - Assistant Clinical Professor of Family Medicine and Comprehensive Care, LSU Health Science Center School of Medicine, Shreveport, Louisiana, USA; Assistant Clinical Professor of Family Medicine, Department of Family and Community Medicine, Tulane University Medical School, New Orleans, Louisiana, USA; Chief Medical Officer, Amedisys, Inc. & Antidote Education Company Disclosures Dr. Ehrlich, Dr. Fleming, DynaMed Editorial Team members, and the staff of Antidote Education Company have disclosed that they have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity. No commercial support has been received for this activity. Accreditation Statements ACCME: This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Antidote EducationCompany and EBSCO Publishing. Antidote is accredited by the ACCME to provide continuing medical education for physicians. Antidote Education Company designates this enduring activity for a maximum of 0.25 AMA PRA Category 1 Credits^TM. Physicians should only claim credit commensurate with the extent of their participation in the activity. AAFP: Enduring Material activity, DynaMed EBM Focus, has been reviewed and is acceptable for up to 13 Prescribed credits by the American Academy of Family Physicians. AAFP certification begins March 7, 2012. Term of approval is for one year from this date with the option of yearly renewal. Each EBM Focus is worth .25 Prescribed credits. Physicians should claim only the credit commensurate with the extent of their participation in the activity. AANP: This program is approved for 0.25 contact hour of continuing education by the American Academy of Nurse Practitioners. Program ID: 1210392X		Last week 476 articles were evaluated via DynaMed's Systematic Literature Surveillance and 250 were added to DynaMed content. Based on criteria for selecting "articles most likely to change clinical practice," one article of significant interest was selected by the DynaMed Editorial Team. Ramipril Improves Walking Ability in Selected Patients with Stable PAD and Intermittent Claudication About a third of patients with peripheral arterial disease (PAD) suffer from intermittent claudication that is relieved with rest. Cilostazol has been recommended by the American College of Cardiology/American Heart Association (J Am Coll Cardiol 2006 Mar 21;47(6):1239) for patients with PAD and claudication, but cilostazol and pentoxifylline, the only FDA-approved drugs for claudication, are each associated with relatively small improvements in walking performance (Cochrane Database Syst Rev 2008 Jan 23;(1):CD003748, Cochrane Database Syst Rev 2012 Jan 18;(1):CD005262, Br J Surg 2012 Dec;99(12):1630). A recent systematic review of small randomized trials assessing ACE inhibitors as a class found no overall improvements in walking (Int J Surg 2011;9(3):209). However, one of the included trials with 40 patients did show a benefit with the ACE inhibitor ramipril. Now, new a larger trial of ramipril provides strong evidence for its efficacy for claudication. A total of 212 patients (mean age 66 years, 83% men) with stable PAD and intermittent claudication were randomized to ramipril 10 mg/day orally vs. placebo for 24 weeks. All patients were on a stable drug regimen for at least 6 months prior to randomization (55% taking antiplatelet agents, 55% taking statins, 9.4% taking cilostazol). The list of exclusion criteria was long, and included blood pressure ≥ 160/100 mmHg, use of ACE inhibitors or ARBs within 6 months, and any condition other than PAD that limited walking. Quality of life was assessed using the SF-36. Walking performance was assessed at baseline and at 6-months by a treadmill test (3.2 km/hour [2 miles/hour] and 12% grade). At baseline, the mean pain-free walking times were 140 seconds for the ramipril group and 144 seconds for the placebo group. The mean maximum walking times were 234 seconds (ramipril) and 238 seconds (placebo). At 6 months, the pain-free walking time was increased by mean 88 seconds with ramipril vs. mean 14 seconds with placebo (p < 0.001), corresponding to an increased walking distance of 184 meters with ramipril (level 1 [likely reliable] evidence). Maximum walking times were increased by mean 277 seconds vs. 23 seconds (p < 0.001). Ramipril was also associated with improvements in patient-reported walking distance, walking speed, and stair climbing (p < 0.001 for each), and in quality of life on the physical component of the SF-36 (p = 0.02) (JAMA 2013 Feb 6;309(5):453). Whether these findings can be generalized to a larger PAD population, including patients with a greater degree of hypertension, or with comorbidities that also limit walking are questions for further study. For more information, see the Peripheral arterial disease (PAD) of lower extremities topic in DynaMed. Call for Peer Reviews We are current seeking reviewers for: Chronic thromboembolic pulmonary hypertension Kaposi sarcoma Learn more about the DynaMed Contribution Opportunities DynaMed Peer Review Editorial Policies for Reviewers Education for Clinicians in Training