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doi:10.12788/jfp.0115

Applied Evidence

How to refine your approach to peripheral arterial disease

J Fam Pract. 2020 December;69(10):500-506 | 10.12788/jfp.0115

By

Dustin K. Smith, DO

Michael J. Arnold, MD

Job Larson, MD

Early recognition, management of comorbid conditions, and appropriate treatment of peripheral arterial disease can help you improve your patient’s outcome.

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PRACTICE RECOMMENDATIONS

❯ Use the ankle-brachial index for diagnosis in patients with history/physical exam findings suggestive of peripheral arterial disease (PAD). A

❯ Strongly encourage smoking cessation in patients with PAD as doing so reduces 5-year mortality and amputation rates. B

❯ Use structured exercise programs for patients with intermittent claudication prior to consideration of revascularization; doing so offers similar benefit and lower risks. A

❯ Recommend revascularization for patients who have limb ischemia or lifestyle-limiting claudication despite medical and exercise therapy. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

References

1. Eraso LH, Fukaya E, Mohler ER 3rd, et al. Peripheral arterial disease, prevalence and cumulative risk factor profile analysis. Eur J Prev Cardiol. 2014;21:704-711.

2. Pasternak RC, Criqui MH, Benjamin EJ, et al; American Heart Association. Atherosclerotic Vascular Disease Conference: Writing Group I: epidemiology. Circulation. 2004;109:2605-2612.

3. Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001;286:1317-1324.

4. Olin JW, Sealove BA. Peripheral artery disease: current insight into the disease and its diagnosis and management. Mayo Clin Proc. 2010;85:678-692.

5. Andras A, Ferkert B. Screening for peripheral arterial disease. Cochrane Database Syst Rev. 2014;(4):CD010835.

6. Guirguis-Blake JM, Evans CV, Redmond N, et al. Screening for peripheral artery disease using ankle-brachial index: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2018;320:184-196.

7. US Preventive Services Task Force. Screening for peripheral artery disease and cardiovascular disease risk assessment with ankle-brachial index: US Preventive Services Task Force recommendation statement. JAMA. 2018;230:177-183.

8. American Heart Association Writing Group 2. Atherosclerotic Peripheral Vascular Disease Symposium II: screening for atherosclerotic vascular diseases: should nationwide programs be instituted? Circulation. 2008;118:2830-2836.

9. Berger JS, Hochman J, Lobach I, et al. Modifiable risk factor burden and the prevalence of peripheral artery disease in different vascular territories. J Vasc Surg. 2013;58:673-681.

10. Joosten MM, Pai JK, Bertoia ML, et al. Associations between conventional cardiovascular risk factors and risk of peripheral artery disease in men. JAMA. 2012;308:1660-1667.

11. Carmelli D, Fabsitz RR, Swan GE, et al. Contribution of genetic and environmental influences to ankle-brachial blood pressure index in the NHLBI Twin Study. National Heart, Lung, and Blood Institute. Am J Epidemiol. 2000;151:452-458.

12. Aboyans V, Criqui MH, Denenberg JO, et al. Risk factors for progression of peripheral arterial disease in large and small vessels. Circulation. 2006;113:2623-2629.

13. Gerald-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135:e726-e779.

14. McDermott MM, Greenland P, Liu K, et al. Leg symptoms in peripheral arterial disease: associated clinical characteristics and functional impairment. JAMA. 2001;286:1599-1606.

15. Cranley JJ. Ischemic rest pain. Arch Surg. 1969;98:187-188.

16. Khan NA, Rahim SA, Anand SS, et al. Does the clinical examination predict lower extremity peripheral arterial disease? JAMA. 2006;295:536-546.

17. Wennberg PW. Approach to the patient with peripheral arterial disease. Circulation. 2013;128:2241-2250.

18. Norgren L, Hiatt WR, Dormandy JA, et al. Inter-society consensus for the management of peripheral arterial disease (TASC II). Eur J Vas Endovasc Surg. 2007;33:S1-S75.

19. Armstrong EJ, Wu J, Singh GD, et al. Smoking cessation is associated with decreased mortality and improved amputation-free survival among patients with symptomatic peripheral artery disease. J Vasc Surg. 2014;60:1565-1571.

20. Lane R, Harwood A, Watson L, et al. Exercise for intermittent claudication. Cochrane Database Syst Rev. 2017;(12):CD000990.

21. Murphy TP, Cutlip DE, Regensteiner JG, et al; CLEVER Study Investigators. Supervised exercise versus primary stenting for claudication resulting from aortoiliac peripheral artery disease: six-month outcomes from the claudication: exercise versus endoluminal revascularization (CLEVER) study. Circulation. 2012;125:130-139.

22. Fakhry F, Fokkenrood HJP, Pronk S, et al. Endovascular revascularization versus conservative management for intermittent claudication. Cochrane Database Syst Rev. 2018;(3):CD010512.

23. Hageman D, Fokkenrood HJ, Gommans LN, et al. Supervised exercise therapy versus home-based exercise therapy versus walking advice for intermittent claudication. Cochrane Database Syst Rev. 2018;(4):CD005263.

24. McDermott MM, Spring B, Berger JS, et al. Effect of a home-based exercise intervention of wearable technology and telephone coaching on walking performance in peripheral artery disease: the HONOR randomized clinical trial. JAMA. 2018;319:1665-1676.

25. Ruiz-Canela M, Estruch R, Corella D, et al. Association of Mediterranean diet with peripheral artery disease: the PREDIMED randomized trial. JAMA. 2014;311:415-417.

26. Zahradka P, Wright B, Weighell W, et al. Daily non-soy legume consumption reverses vascular impairment due to peripheral artery disease. Atherosclerosis. 2013;230:310-314.

27. Heart Protection Study Collaborative Group. Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20536 people with peripheral arterial disease and other high-risk conditions. J Vasc Surg. 2007;45:645-655.

28. Kumbhani DJ, Steg G, Cannon CP, et al. Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the REACH registry. Eur Heart J. 2014;35:2864-2872.

29. Wong PF, Chong LY, Mikhailidis DP, et al. Antiplatelet agents for intermittent claudication. Cochrane Database Syst Rev. 2011;(11):CD001272.

30. Critical Leg Ischaemia Prevention Study (CLIPS) Group, Catalano M, Born G, Peto R. Prevention of serious vascular events by aspirin amongst patients with peripheral arterial disease: randomized, double-blind trial. J Intern Med. 2007;261:276-284.

31. Morley RL, Sharma A, Horsch AD, et al. Peripheral artery disease. BMJ. 2018;360:j5842.

32. Bedenis R, Stewart M, Cleanthis M, et al. Cilostazol for intermittent claudication. Cochrane Database Syst Rev. 2014;(10):CD003748.

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33. Salhiyyah K, Forster R, Senanayake E, et al. Pentoxifylline for intermittent claudication. Cochrane Database Syst Rev. 2015;(9):CD005262.

34. Stewart M, Morling JR, Maxwell H. Padma 28 for intermittent claudication. Cochrane Database Syst Rev. 2016;(3):CD007371.

35. Kleijnen J, Mackerras D. Vitamin E for intermittent claudication. Cochrane Database Syst Rev. 1998;(1):CD000987.

36. Nicolai SPA, Kruidenior LM, Bendermacher BLW, et al. Ginkgo biloba for intermittent claudication. Cochrane Database Syst Rev. 2013;(6):CD006888.

37. Campbell A, Price J, Hiatt WR. Omega-3 fatty acids for intermittent claudication. Cochrane Database Syst Rev. 2013;(7):CD003833.

38. American Surgical Association, New York Surgical Society, Philadelphia Academy of Surgery, Southern Surgical Association (US), Central Surgical Association. Results of a prospective randomized trial evaluating surgery versus thrombolysis for ischemia of the lower extremity: the STILE trial. Ann Surg. 1994;220:251-268.

39. Ouriel K, Veith FJ, Sasahara AA. Thrombolysis or peripheral arterial surgery: phase I results. TOPAS Investigators. J Vasc Surg. 1996;23:64-73.

40. Bradbury AW, Ruckley CV, Fowkes FGR, et al. Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised, controlled trial. Lancet. 2005;366:1925-1934.

41. Criqui MH, Langer RD, Fronek A, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med. 1992;326:381-386.

Peripheral arterial disease (PAD), the progressive disorder that results in ischemia to distal vascular territories as a result of atherosclerosis, spans a wide range of presentations, from minimally symptomatic disease to limb ischemia secondary to acute or chronic occlusion.

The prevalence of PAD is variable, due to differing diagnostic criteria used in studies, but PAD appears to affect 1 in every 22 people older than age 40.¹ However, since PAD incidence increases with age, it is increasing in prevalence as the US population ages.^1-3

PAD is associated with increased hospitalizations and decreased quality of life.⁴ Patients with PAD have an estimated 30% 5-year risk for myocardial infarction, stroke, or death from a vascular cause.³

Screening. Although PAD is underdiagnosed and appears to be undertreated,³ population-based screening for PAD in asymptomatic patients is not recommended. A Cochrane review found no studies evaluating the benefit of asymptomatic population-based screening.⁵ Similarly, in 2018, the USPSTF performed a comprehensive review and found no studies to support routine screening and determined there was insufficient evidence to recommend it.^6,7

Risk factors and associated comorbidities

PAD risk factors, like the ones detailed below, have a potentiating effect. The presence of 2 risk factors doubles PAD risk, while 3 or more risk factors increase PAD risk by a factor of 10.¹

Increasing age is the greatest single risk factor for PAD.^1,2,8,9Researchers using data from the National Health and Nutrition Examination Survey (NHANES) found that the prevalence of PAD increased from 1.4% in individuals ages 40 to 49 years to almost 17% in those age 70 or older.¹

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Patients with PAD have an estimated 30% 5-year risk for myocardial infarction, stroke, or death from a vascular cause.

Demographic characteristics. Most studies demonstrate a higher risk for PAD in men.^1-3,10 African-American patients have more than twice the risk for PAD, compared with Whites, even after adjustment for the increased prevalence of associated diseases such as hypertension and diabetes in this population.^1-3,10

Continue to: Genetics...

References

1. Eraso LH, Fukaya E, Mohler ER 3rd, et al. Peripheral arterial disease, prevalence and cumulative risk factor profile analysis. Eur J Prev Cardiol. 2014;21:704-711.

2. Pasternak RC, Criqui MH, Benjamin EJ, et al; American Heart Association. Atherosclerotic Vascular Disease Conference: Writing Group I: epidemiology. Circulation. 2004;109:2605-2612.

3. Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001;286:1317-1324.

4. Olin JW, Sealove BA. Peripheral artery disease: current insight into the disease and its diagnosis and management. Mayo Clin Proc. 2010;85:678-692.

5. Andras A, Ferkert B. Screening for peripheral arterial disease. Cochrane Database Syst Rev. 2014;(4):CD010835.

6. Guirguis-Blake JM, Evans CV, Redmond N, et al. Screening for peripheral artery disease using ankle-brachial index: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2018;320:184-196.

7. US Preventive Services Task Force. Screening for peripheral artery disease and cardiovascular disease risk assessment with ankle-brachial index: US Preventive Services Task Force recommendation statement. JAMA. 2018;230:177-183.

8. American Heart Association Writing Group 2. Atherosclerotic Peripheral Vascular Disease Symposium II: screening for atherosclerotic vascular diseases: should nationwide programs be instituted? Circulation. 2008;118:2830-2836.

9. Berger JS, Hochman J, Lobach I, et al. Modifiable risk factor burden and the prevalence of peripheral artery disease in different vascular territories. J Vasc Surg. 2013;58:673-681.

10. Joosten MM, Pai JK, Bertoia ML, et al. Associations between conventional cardiovascular risk factors and risk of peripheral artery disease in men. JAMA. 2012;308:1660-1667.

11. Carmelli D, Fabsitz RR, Swan GE, et al. Contribution of genetic and environmental influences to ankle-brachial blood pressure index in the NHLBI Twin Study. National Heart, Lung, and Blood Institute. Am J Epidemiol. 2000;151:452-458.

12. Aboyans V, Criqui MH, Denenberg JO, et al. Risk factors for progression of peripheral arterial disease in large and small vessels. Circulation. 2006;113:2623-2629.

13. Gerald-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135:e726-e779.

14. McDermott MM, Greenland P, Liu K, et al. Leg symptoms in peripheral arterial disease: associated clinical characteristics and functional impairment. JAMA. 2001;286:1599-1606.

15. Cranley JJ. Ischemic rest pain. Arch Surg. 1969;98:187-188.

16. Khan NA, Rahim SA, Anand SS, et al. Does the clinical examination predict lower extremity peripheral arterial disease? JAMA. 2006;295:536-546.

17. Wennberg PW. Approach to the patient with peripheral arterial disease. Circulation. 2013;128:2241-2250.

18. Norgren L, Hiatt WR, Dormandy JA, et al. Inter-society consensus for the management of peripheral arterial disease (TASC II). Eur J Vas Endovasc Surg. 2007;33:S1-S75.

19. Armstrong EJ, Wu J, Singh GD, et al. Smoking cessation is associated with decreased mortality and improved amputation-free survival among patients with symptomatic peripheral artery disease. J Vasc Surg. 2014;60:1565-1571.

20. Lane R, Harwood A, Watson L, et al. Exercise for intermittent claudication. Cochrane Database Syst Rev. 2017;(12):CD000990.

21. Murphy TP, Cutlip DE, Regensteiner JG, et al; CLEVER Study Investigators. Supervised exercise versus primary stenting for claudication resulting from aortoiliac peripheral artery disease: six-month outcomes from the claudication: exercise versus endoluminal revascularization (CLEVER) study. Circulation. 2012;125:130-139.

22. Fakhry F, Fokkenrood HJP, Pronk S, et al. Endovascular revascularization versus conservative management for intermittent claudication. Cochrane Database Syst Rev. 2018;(3):CD010512.

23. Hageman D, Fokkenrood HJ, Gommans LN, et al. Supervised exercise therapy versus home-based exercise therapy versus walking advice for intermittent claudication. Cochrane Database Syst Rev. 2018;(4):CD005263.

24. McDermott MM, Spring B, Berger JS, et al. Effect of a home-based exercise intervention of wearable technology and telephone coaching on walking performance in peripheral artery disease: the HONOR randomized clinical trial. JAMA. 2018;319:1665-1676.

25. Ruiz-Canela M, Estruch R, Corella D, et al. Association of Mediterranean diet with peripheral artery disease: the PREDIMED randomized trial. JAMA. 2014;311:415-417.

26. Zahradka P, Wright B, Weighell W, et al. Daily non-soy legume consumption reverses vascular impairment due to peripheral artery disease. Atherosclerosis. 2013;230:310-314.

27. Heart Protection Study Collaborative Group. Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20536 people with peripheral arterial disease and other high-risk conditions. J Vasc Surg. 2007;45:645-655.

28. Kumbhani DJ, Steg G, Cannon CP, et al. Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the REACH registry. Eur Heart J. 2014;35:2864-2872.

29. Wong PF, Chong LY, Mikhailidis DP, et al. Antiplatelet agents for intermittent claudication. Cochrane Database Syst Rev. 2011;(11):CD001272.

30. Critical Leg Ischaemia Prevention Study (CLIPS) Group, Catalano M, Born G, Peto R. Prevention of serious vascular events by aspirin amongst patients with peripheral arterial disease: randomized, double-blind trial. J Intern Med. 2007;261:276-284.

31. Morley RL, Sharma A, Horsch AD, et al. Peripheral artery disease. BMJ. 2018;360:j5842.

32. Bedenis R, Stewart M, Cleanthis M, et al. Cilostazol for intermittent claudication. Cochrane Database Syst Rev. 2014;(10):CD003748.

33. Salhiyyah K, Forster R, Senanayake E, et al. Pentoxifylline for intermittent claudication. Cochrane Database Syst Rev. 2015;(9):CD005262.

34. Stewart M, Morling JR, Maxwell H. Padma 28 for intermittent claudication. Cochrane Database Syst Rev. 2016;(3):CD007371.

35. Kleijnen J, Mackerras D. Vitamin E for intermittent claudication. Cochrane Database Syst Rev. 1998;(1):CD000987.

36. Nicolai SPA, Kruidenior LM, Bendermacher BLW, et al. Ginkgo biloba for intermittent claudication. Cochrane Database Syst Rev. 2013;(6):CD006888.

37. Campbell A, Price J, Hiatt WR. Omega-3 fatty acids for intermittent claudication. Cochrane Database Syst Rev. 2013;(7):CD003833.

38. American Surgical Association, New York Surgical Society, Philadelphia Academy of Surgery, Southern Surgical Association (US), Central Surgical Association. Results of a prospective randomized trial evaluating surgery versus thrombolysis for ischemia of the lower extremity: the STILE trial. Ann Surg. 1994;220:251-268.

39. Ouriel K, Veith FJ, Sasahara AA. Thrombolysis or peripheral arterial surgery: phase I results. TOPAS Investigators. J Vasc Surg. 1996;23:64-73.

40. Bradbury AW, Ruckley CV, Fowkes FGR, et al. Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised, controlled trial. Lancet. 2005;366:1925-1934.

41. Criqui MH, Langer RD, Fronek A, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med. 1992;326:381-386.

How to refine your approach to peripheral arterial disease

PRACTICE RECOMMENDATIONS

References

Risk factors and associated comorbidities

Pages

Recommended Reading