Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Established and evolving medical therapies for claudication in patients with peripheral arterial disease

Nature Clinical Practice Cardiovascular Medicine volume 3, pages 604–610 (2006)Cite this article

Abstract

Claudication resulting from peripheral arterial disease causes substantial impairment in the ability to carry out normal daily activities. The medical treatments for claudication that are currently available are exercise rehabilitation and one drug, cilostazol. Pentoxifylline, which improves red cell deformability, lowers fibrinogen levels and decreases platelet aggregation, has been used historically, but frequency of use has declined because of limited effectiveness. Exercise rehabilitation, while efficacious, has been underused in the past. This therapy is, however, currently the subject of several large research projects. These studies are investigating mechanisms by which exercise therapy could benefit people with claudication and are also directly comparing it with other therapies. Concurrently, several new drug therapies for claudication are in the process of being evaluated. These research efforts might increase the available armamentarium and thereby help to alleviate the impairments associated with this symptom. The aim of this article is to discuss the current medical treatments being developed for use in patients with claudication resulting from peripheral arterial disease.

Key Points

  • Peripheral arterial disease is a common form of atherosclerotic disease

  • Claudication is a disabling symptom of peripheral arterial disease, but few medical treatments are available to treat the condition

  • Numerous agents are currently under evaluation as claudication therapies

  • Exercise training is an efficacious therapy for claudication but is underused in the clinical setting

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Criqui MH et al. (1985) The prevalence of peripheral arterial disease in a defined population. Circulation 71: 510–515

    Article  CAS  Google Scholar 

  2. Hiatt WR et al. (1995) Effect of diagnostic criteria on the prevalence of peripheral arterial disease. The San Luis Valley diabetes study. Circulation 91: 1472–1479

    Article  CAS  Google Scholar 

  3. Criqui MH et al. (1997) The epidemiology of peripheral arterial disease: importance of identifying the population at risk. Vasc Med 2: 221–226

    Article  CAS  Google Scholar 

  4. Centers for Disease Control and Prevention (2005) Lower extremity disease among persons aged ≥40 years with and without diabetes—United States, 1999–2002. MMWR Morb Mortal Wkly Rep 54: 1158–1160

  5. Hiatt WR (2005) The US experience with cilostazol in treating intermittent claudication. Atheroscler Suppl 6: 21–31

    Article  CAS  Google Scholar 

  6. Regensteiner JG and Hiatt WR (2002) Current medical therapies for patients with peripheral arterial disease: a critical review. Am J Med 112: 49–57

    Article  Google Scholar 

  7. Hirsch AT et al. (2006) ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. J Am Coll Cardiol 47: 1239–1312

    Article  Google Scholar 

  8. Hirsch AT et al. (2001) Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA 286: 1317–1324

    Article  CAS  Google Scholar 

  9. Criqui MH et al. (1996) The correlation between symptoms and non-invasive test results in patients referred for peripheral arterial disease testing. Vasc Med 1: 65–71

    Article  CAS  Google Scholar 

  10. Hiatt WR et al. (1990) Benefit of exercise conditioning for patients with peripheral arterial disease. Circulation 81: 602–609

    Article  CAS  Google Scholar 

  11. Carter SA (1969) Clinical measurement of systolic pressures in limbs with arterial occlusive disease. JAMA 207: 1869–1874

    Article  CAS  Google Scholar 

  12. Hiatt WR et al. (1988) The evaluation of exercise performance in patients with peripheral vascular disease. J Cardiopulm Rehabil 12: 525–532

    Article  Google Scholar 

  13. Labs KH et al. (1999) Reliability of treadmill testing in peripheral arterial disease: a comparison of a constant load with a graded load treadmill protocol. Vasc Med 4: 239–246

    Article  CAS  Google Scholar 

  14. Regensteiner JG et al. (1996) Exercise training improves functional status in patients with peripheral arterial disease. J Vasc Surg 23: 104–115

    Article  CAS  Google Scholar 

  15. Regensteiner JG et al. (2002) Effect of cilostazol on community-based walking ability and health-related quality of life in patients with peripheral arterial disease: results of six randomized controlled trials. J Am Geriatr Soc 50: 1939–1946

    Article  Google Scholar 

  16. McDermott MM et al. (1998) Measurement of walking endurance and walking velocity with questionnaire: validation of the walking impairment questionnaire in men and women with peripheral arterial disease. J Vasc Surg 28: 1072–1081

    Article  CAS  Google Scholar 

  17. Regensteiner JG et al. (1993) Functional benefits of peripheral vascular bypass surgery for patients with intermittent claudication. Angiology 44: 1–10

    Article  CAS  Google Scholar 

  18. Porter JM et al. (1982) Pentoxifylline efficacy in the treatment of intermittent claudication: multicenter controlled double-blind trial with objective assessment of chronic occlusive arterial disease patients. Am Heart J 104: 66–72

    Article  CAS  Google Scholar 

  19. Dawson DL et al. (2000) A comparison of cilostazol and pentoxifylline for treating intermittent claudication. Am J Med 109: 523–530

    Article  CAS  Google Scholar 

  20. Packer M et al. (1991) Effect of oral milrinone on mortality in severe chronic heart failure, The PROMISE Study Research Group. N Engl J Med 325: 1468–1475

    Article  CAS  Google Scholar 

  21. The Scandinavian Simvastatin Survival Study group (1994) Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344: 1383–1389

  22. Mohler ER III et al. (2003) Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease. Circulation 108: 1481–1486

    Article  CAS  Google Scholar 

  23. McDermott MM et al. (2003) Statin use and leg functioning in patients with and without lower-extremity peripheral arterial disease. Circulation 107: 757–761

    Article  CAS  Google Scholar 

  24. Mondillo S et al. (2003) Effects of simvastatin on walking performance and symptoms of intermittent claudication in hypercholesterolemic patients with peripheral vascular disease. Am J Med 114: 359–364

    Article  CAS  Google Scholar 

  25. Brevetti G et al. (1995) Propionyl-9 pt-carnitine in intermittent claudication: double-blind, placebo-controlled, dose titration, multicenter study. J Am Coll Cardiol 26: 1411–1416

    Article  CAS  Google Scholar 

  26. Hiatt WR et al. (2001) Propionyl-l-carnitine improves exercise performance and functional status in patients with claudication. Am J Med 110: 616–622

    Article  CAS  Google Scholar 

  27. Brevetti G et al. (1999) European multicenter study on propionyl-L-carnitine in intermittent claudication. J Am Coll Cardiol 34: 1618–1624

    Article  CAS  Google Scholar 

  28. Khan TA et al. (2003) Gene therapy progress and prospects: therapeutic angiogenesis for limb and myocardial ischemia. Gene Ther 10: 285–291

    Article  CAS  Google Scholar 

  29. Lederman RJ et al. (2002) Therapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (the TRAFFIC study): a randomised trial. Lancet 359: 2053–2058

    Article  CAS  Google Scholar 

  30. Rajagopalan S et al. (2003) Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: a phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication. Circulation 108: 1933–1938

    Article  CAS  Google Scholar 

  31. Ahimastos AA et al. (2006) Brief communication: ramipril markedly improves walking ability in patients with peripheral arterial disease: a randomized trial. Ann Intern Med 144: 660–664

    Article  CAS  Google Scholar 

  32. Horsch S and Walther C (2004) Ginkgo biloba special extract EGb 761 in the treatment of peripheral arterial occlusive disease (PAOD)—a review based on randomized, controlled studies. Int J Clin Pharmacol Ther 42: 63–72

    Article  CAS  Google Scholar 

  33. Gardner AW and Poehlman ET (1995) Exercise rehabilitation programs for the treatment of claudication pain. A meta-analysis. JAMA 274: 975–980

    Article  CAS  Google Scholar 

  34. Regensteiner JG (1997) Exercise in the treatment of claudication: assessment and treatment of functional impairment. Vasc Med 2: 238–242

    Article  CAS  Google Scholar 

  35. Robeer GG et al. (1998) Exercise therapy for intermittent claudication: a review of the quality of randomised clinical trials and evaluation of predictive factors. Eur J Vasc Endovasc Surg 15: 36–43

    Article  CAS  Google Scholar 

  36. Leng GC et al. (2000) Exercise for intermittent claudication. The Cochrane Database of Systematic Reviews, Issue 1, Art. No CD000990

  37. Tsai JC et al. (2002) The effects of exercise training on walking function and perception of health status in elderly patients with peripheral arterial occlusive disease. J Intern Med 252: 448–455

    Article  CAS  Google Scholar 

  38. Stewart KJ et al. (2002) Exercise training for claudication. N Engl J Med 347: 1941–1951

    Article  Google Scholar 

  39. Gardner AW et al. (2002) Effects of long-term exercise rehabilitation on claudication distances in patients with peripheral arterial disease: a randomized controlled trial. J Cardiopulm Rehabil 22: 192–198

    Article  Google Scholar 

  40. Alpert JS et al. (1969) Exercise and intermittent claudication. Blood flow in the calf muscle during walking studied by the xenon-133 clearance method. Circulation 39: 353–359

    Article  CAS  Google Scholar 

  41. Clifford PC et al. (1980) Intermittent claudication: is a supervised exercise class worth while? Br Med J 280: 1503–1505

    Article  CAS  Google Scholar 

  42. Gardner AW et al. (2000) Improved functional outcomes following exercise rehabilitation in patients with intermittent claudication. J Gerontol A Biol Sci Med Sci 55: M570–M577

    Article  CAS  Google Scholar 

  43. Gibellini R et al. (2000) Exercise training in intermittent claudication. Int Angiol 19: 8–13

    CAS  PubMed  Google Scholar 

  44. Wolosker N et al. (2003) Evaluation of walking capacity over time in 500 patients with intermittent claudication who underwent clinical treatment. Arch Intern Med 163: 2296–2300

    Article  Google Scholar 

  45. Izquierdo-Porrera AM et al. (2000) Effects of exercise rehabilitation on cardiovascular risk factors in older patients with peripheral arterial occlusive disease. J Vasc Surg 31: 670–677

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Professor of Medicine in the Divisions of General Internal Medicine and Cardiology,

    Judith G Regensteiner & Kerry J Stewart

  2. Director of the Center for Women's Health Research, University of Colorado at Denver and Health Sciences Center, Denver, CO

    Judith G Regensteiner & Kerry J Stewart

  3. Professor of Medicine in the Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Judith G Regensteiner & Kerry J Stewart

Authors
  1. Judith G Regensteiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kerry J Stewart
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Judith G Regensteiner.

Ethics declarations

Competing interests

Judith G Regensteiner is on the Speaker Bureau of Sanofi-Aventis. She currently receives funding for research into the mechanisms by which exercise training improves claudication as well as a comparison of exercise training and angioplasty from the National Institutes of Health. She is participating in a clinical trial of statins to treat claudication supported by KOS pharmaceuticals.

KJ Stewart has received funding from the NIH.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Regensteiner, J., Stewart, K. Established and evolving medical therapies for claudication in patients with peripheral arterial disease. Nat Rev Cardiol 3, 604–610 (2006). https://doi.org/10.1038/ncpcardio0660

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpcardio0660

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing