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Pharmacological Treatment of Patients with Peripheral Arterial Disease

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Abstract

Atherosclerosis is a disease process that affects the coronary, cerebral and peripheral arterial circulation. While great emphasis has been placed on the aggressive pharmacological management of coronary artery disease, less attention has been paid to the pharmacological management of peripheral vascular disease, despite its significant morbidity and mortality. The purpose of medical management in peripheral arterial disease is to relieve symptoms of claudication and to prevent thrombotic vascular events. These goals are best achieved through aggressive risk factor modification and pharmacotherapy. Risk factor modification includes smoking cessation, adequate control of blood pressure and cholesterol, as well as aggressive glycaemic control in patients with diabetes mellitus. Antiplatelet therapy and relief of claudication is also achieved through pharmacotherapy. With aggressive risk factor modification and adequate pharmacotherapy, patients with peripheral arterial disease can have an improved quality of life as well as prolonged survival.

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References

  1. Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990–2020: global burden of disease study. Lancet 1997; 349(24): 1498–504

    Article  PubMed  CAS  Google Scholar 

  2. Criqui MH, Fronek A, Barrett-Connor E, et al. The prevalence of peripheral arterial disease in a defined population. Circulation 1985; 71: 510–5

    Article  PubMed  CAS  Google Scholar 

  3. Hiatt WR, Hoag S, Hamman RF. Effect of diagnostic criteria on the prevalence of peripheral arterial disease: the San Luis Valley Diabetes Study. Circulation 1995; 91: 1472–9

    Article  PubMed  CAS  Google Scholar 

  4. Kannel WB. The demographics of claudication and the aging of the American population. Vasc Med 1996; 1: 60–4

    PubMed  CAS  Google Scholar 

  5. Stoffers HE, Rinkens PE, Rester AD, et al. The prevalence of asymptomatic and unrecognized peripheral arterial occlusive disease. Int J Epidemiol 1996; 25: 282–90

    Article  PubMed  CAS  Google Scholar 

  6. Kannel WB, Skinner JJJ, Schwartz MJ, et al. Intermittent claudication: incidence in the Framingham Study. Circulation 1970; 41: 875–83

    Article  PubMed  CAS  Google Scholar 

  7. Kannel WB, McGee DL. Update on some epidemiologic features of intermittent claudication: the Framingham Study. J Am Geriatr Soc 1985; 33: 13–8

    PubMed  CAS  Google Scholar 

  8. Hirsch AT, Criqui MH, Treat-Jacobson D. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA 2001 Sep 19; 286(11): 1317–24

    Article  PubMed  CAS  Google Scholar 

  9. McDermott MM, Greenland P, Liu K, et al. Leg symptoms in peripheral arterial disease. JAMA 2001; 286: 1599–606

    Article  PubMed  CAS  Google Scholar 

  10. Leng GC, Lee AJ, Flowked FG, et al. Incidence, natural history and cardiovascular events in symptomatic and asymptomatic peripheral artery disease in the general population. Int J Epidemiol 1996; 25: 1172–81

    Article  PubMed  CAS  Google Scholar 

  11. Leng GC, Fowkes FG, Lee AJ, et al. Use of ankle brachial pressure index to predict cardiovascular events and death: a cohort study. BMJ 1996; 313: 1440–4

    Article  PubMed  CAS  Google Scholar 

  12. Dormandy J, Heeck L, Vig S. The natural history of claudication: risk to life and limb. Semin Vasc Surg 1999; 12: 123–37

    PubMed  CAS  Google Scholar 

  13. Hertzer NR, Beven EG, Young JR, et al. Coronary artery disease in peripheral vascular patients: a classification of 1000 coronary angiograms and results of surgical management. Ann Surg 1984; 199: 223–33

    Article  PubMed  CAS  Google Scholar 

  14. Dormandy J, Mahir M, Ascady G, et al. Fate of the patient with chronic leg ischemia: a review article. J Cardiovasc Surg 1989; 30: 50–7

    CAS  Google Scholar 

  15. Aronow WS, Ahn C. Prevalence of coexistence of coronary artery disease, peripheral arterial disease, and atherothrombotic brain infarction in men and women ≥62 years of age. Am J Cardiol 1994; 74: 64–5

    Article  PubMed  CAS  Google Scholar 

  16. Ness J, Aronow WS. Prevalence of coexistence of coronary artery disease, ischemic stroke, and peripheral arterial disease in older persons, mean age 80 years, in an academic hospital-based geriatric practice. J Am Geriatr Soc 1999; 47: 1255–6

    PubMed  CAS  Google Scholar 

  17. McDermott MM, Mehta S, Ahn H, et al. Atherosclerotic risk factors are less intensively treated in patients with peripheral arterial disease than in patients with coronary artery disease. JGen Intern Med 1997; 12: 209–15

    Article  CAS  Google Scholar 

  18. Faulkner KW, House AK, Castleden WM. The effect of cessation of smoking on the accumulative survival rates of patients with symptomatic peripheral vascular disease. Med J Aust 1983; 1: 217–9

    PubMed  CAS  Google Scholar 

  19. Leng GC, Papacosta O, Whincup P, et al. Femoral atherosclerosis in an older British population: prevalence and risk factors. Atherosclerosis 2000; 152: 167–74

    Article  PubMed  CAS  Google Scholar 

  20. Jonason T, Ringqvist I. Factors of prognostic importance for subsequent rest pain in patients with intermittent claudication. Acta Med Scand 1985; 218: 27–33

    Article  PubMed  CAS  Google Scholar 

  21. Hirsch AT, Treat-Jacobson D, Lando HA, et al. The role of tobacco cessation, antiplatelet and lipid-lowering therapies in the treatment of peripheral arterial disease. Vasc Med 1997; 2: 243–51

    PubMed  CAS  Google Scholar 

  22. Ameli FM, Stein M, Provan JL, et al. The effect of postoperative smoking on femoropopliteal bypass grafts. Ann Vasc Surg 1989; 3: 20–5

    Article  PubMed  CAS  Google Scholar 

  23. Silagy C, Mant D, Fowler G, et al. Meta-analysis on efficacy of nicotine replacement therapies in smoking cessation. Lancet 1994; 343: 139–42

    Article  PubMed  CAS  Google Scholar 

  24. Hurt RD, Sachs DPL, Glover ED, et al. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med 1997; 337: 1195–202

    Article  PubMed  CAS  Google Scholar 

  25. Murabito JM, D’Agostino RB, Silbershatz H, et al. Intermittent claudication: a risk profile from the Framingham Heart Study. Circulation 1997; 96: 44–9

    Article  PubMed  CAS  Google Scholar 

  26. Vogt MT, Cauley JA, Kuller LH, et al. Prevalence and correlates of lower extremity arterial disease in elderly women. Am J Epidemiol 1993; 137: 559–68

    PubMed  CAS  Google Scholar 

  27. Safar ME, Lament S, Asmar RE, et al. Systolic hypertension in patients with arteriosclerosis obliterans of the lower limbs. Angiology 1987; 38: 287–95

    Article  PubMed  CAS  Google Scholar 

  28. Collins R, Peto R, MacMahon S, et al. Blood pressure, stroke, and coronary heart disease, II: short-term reductions in blood pressure: overview of randomized drug trials in their epidemiological context. Lancet 1990; 335: 827–38

    Article  PubMed  CAS  Google Scholar 

  29. Solomon SA, Ramsay LE, Yeo WW, et al. Beta blockade and intermittent claudication: placebo controlled trial of atenolol and nifedipine and their combination. BMJ 1991; 303: 1100–4

    Article  PubMed  CAS  Google Scholar 

  30. Hiatt WR, Stoll S, Nies AS. Effect of beta-adrenergic blockers on the peripheral circulation in patients with peripheral vascular disease. Circulation 1985; 72: 1226–31

    Article  PubMed  CAS  Google Scholar 

  31. Radack K, Deck C. Beta-adrenergic blocker therapy does not worsen intermittent claudication in subjects with peripheral arterial disease: a meta-analysis of randomized controlled trials. Arch Intern Med 1991; 151: 1769–76

    Article  PubMed  CAS  Google Scholar 

  32. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Arch Intern Med 1997; 157: 2413–46

    Article  Google Scholar 

  33. Rutherford JD, Pfeffer MA, Moye LA, et al. Effects of captopril on ischemic events after myocardial infarction: results of the Survival and Ventricular Enlargement trial. Circulation 1994; 90: 1731–8

    Article  PubMed  CAS  Google Scholar 

  34. Yusuf S, Pepine CJ, Garces C, et al. Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fractions. Lancet 1992; 340: 1173–8

    Article  PubMed  CAS  Google Scholar 

  35. Dahloef B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For End-pointreduction in hypertension study (LIFE): a randomized trail against atenolol. Lancet 2002; 359: 995–1003

    Article  Google Scholar 

  36. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzymeinhibitor, ramipril, on death from cardiovascular causes. N Engl J Med 2000; 342: 145–53

    Article  PubMed  CAS  Google Scholar 

  37. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian simvastatin survival (4S) study. Lancet 1994; 344: 1383–9

    Google Scholar 

  38. Sacks RM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996; 335: 1001–9

    Article  PubMed  CAS  Google Scholar 

  39. Pedersen TR, Kjekshus J, Pyorala K, et al. Effect of simvastatin on ischemic signs and symptoms in the Scandinavian Simvastatin Survival Study (4S). Am J Cardiol 1998; 81: 333–5

    Article  PubMed  CAS  Google Scholar 

  40. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20536 high-risk individuals: a randomized placebo-controlled trail. Lancet 2002; 360: 7–22

    Article  Google Scholar 

  41. Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001; 285: 2486–97

    Google Scholar 

  42. Clofibrate and niacin in coronary heart disease. JAMA 1975; 231: 360–81

    Article  Google Scholar 

  43. Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol 1986; 8: 1245–55

    Article  PubMed  CAS  Google Scholar 

  44. Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990; 323: 1289–98

    Article  PubMed  CAS  Google Scholar 

  45. Blankenhom D, Nessim S, Johnson R, et al. Beneficial effects combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. JAMA 1987; 257: 3233–40

    Article  Google Scholar 

  46. Elam MB, Hunninghake DB, Davis KB, et al. Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease. The ADMIT Study: a randomized trial. JAMA 2000; 284: 1263–70

    CAS  Google Scholar 

  47. Chesney CM, Elam MB, Herd JA, et al. Effect of niacin, warfarin, and antioxidant therapy on coagulation parameters in patients with peripheral arterial disease in the Arterial Disease Multiple Intervention Trial (ADMIT). Am Heart J 2000; 140: 631–6

    Article  PubMed  CAS  Google Scholar 

  48. Kannel WB, McGee DL. Diabetes and cardiovascular disease: the Framingham Study. JAMA 1979; 241: 2035–8

    Article  PubMed  CAS  Google Scholar 

  49. Kannel WB, D’Agostino RB, Wilson PW, et al. Diabetes, fibrinogen, and risk of cardiovascular disease: the Framingham experience. Am Heart J 1990; 120: 672–6

    Article  PubMed  CAS  Google Scholar 

  50. Donnelly R, Emslie-Smith A, Gardiner I, et al. Vascular complications of diabetes. BMJ 2000; 320: 1062–6

    Article  PubMed  CAS  Google Scholar 

  51. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood glucose control with sulfonylureas or insulin comparedwith conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837–53

    Article  Google Scholar 

  52. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care 2001; 24 Suppl. 1: S33–43

    Article  Google Scholar 

  53. Antiplatelet Trialists’ Collaboration. Collaborative overview of randomized trials of antiplatelet therapy, I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ 1994; 308: 81–106

    Article  Google Scholar 

  54. Antiplatelet Trialists’ Collaboration. Collaborative overview of randomized trials of antiplatelet therapy, II: maintenance of vascular graft or arterial patency by antiplatelet therapy. BMJ 1994; 308: 159–68

    Article  Google Scholar 

  55. Schafer AI. Antiplatelet therapy. Am J Med 1996; 101: 199–209

    Article  PubMed  CAS  Google Scholar 

  56. McCollum C, Alexander C, Kenchington G, et al. Antiplatelet drugs in femoropopliteal vein bypasses: a multicenter trial. J Vasc Surg 1991; 13: 150–61

    Article  PubMed  CAS  Google Scholar 

  57. Janzon L, Bergqvist D, Boberg J, et al. Prevention of myocardial infarction and stroke in patients with intermittent claudication: effects of ticlopidine: results from the STIMS, the Swedish Ticlopidine Multicenter Study. J Intern Med 1990; 227: 301–8

    Article  PubMed  CAS  Google Scholar 

  58. Blanchard J, Carreras LO, Kindermans M, et al. Results of EMATAP: a double-blind placebo-controlled multicenter trial of ticlodipine in patients with peripheral arterial disease. Nouv Rev Fr Hematol 1993; 35: 523–8

    Google Scholar 

  59. Arcan JC, Panak E. Ticlopidine in the treatment of peripheral occlusive arterial disease. Semin Thromb Hemost 1989; 15: 167–70

    Article  PubMed  CAS  Google Scholar 

  60. Balsano F, Coccheri S, Libretti A, et al. Ticlopidine in the treatment of intermittent claudication: a 21-month double-blind trial. J Lab Clin Med 1989; 114: 84–91

    PubMed  CAS  Google Scholar 

  61. Prescribing information: Ticlid® (ticlodipine hydrochloride) tablets. In: Physicians’ Desk Reference®. Montvale (NJ): Medical Economics Co., 2000: 2670–3

    Google Scholar 

  62. CAPRIE Steering Committee. A randomized, blinded, trial of clopidogrel versus aspirin in patients at risk of ischemic events (CAPRIE). Lancet 1996; 348: 1329–39

    Article  Google Scholar 

  63. Tilgren C. Obliterative arterial disease of the lower limbs, IV: evaluation of long-term anticoagulation therapy. Acta Med Scand 1965; 178: 203–19

    Article  Google Scholar 

  64. Smith P, Arneson H, Holme I. The effect of warfarin on mortality and reinfarction after myocardial infarction. N Engl J Med 1990; 232: 147–52

    Article  Google Scholar 

  65. Working party on thrombolysis in the management of limb ischemia. Thrombolysis in the management of lower limb peripheral arterial occlusion-a consensus document. Am J Cardiol 1998; 81: 207–18

    Article  Google Scholar 

  66. Knatterud GL, Rosenberg Y, Campeau L, et al. Long-term effects on clinical outcomes of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation in the post coronary artery bypass graft trial: Post CABG Investigators. Circulation 2000 Jul 11; 102(2): 157–65

    Article  PubMed  CAS  Google Scholar 

  67. Conlan MG, Folsom AR, Finch A, et al. Associations of factor VIII and von Willebrand factor with age, race, sex and risk factors for atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Study. Thromb Haemost 1993; 70: 380–5

    PubMed  CAS  Google Scholar 

  68. Cortellaro M, Cofrancesco E, Boschetti C, et al. Increased fibrin turnover and high PAI-1 activity as predictors of ischemic events in atherosclerotic patients. Arterioscler Thromb 1993; 13: 1412–7

    Article  PubMed  CAS  Google Scholar 

  69. Garg R, Elam MB, Crouse JR, et al. Effective and safe modification of multiple atherosclerotic risk factors in patients with peripheral arterial disease. Am Heart J 2000; 140: 790–803

    Article  Google Scholar 

  70. Angelkort B, Spurk P, Habbaba A, et al. Blood flow properties and walking performance in chronic arterial occlusive disease. Angiology 1985; 36: 285–92

    Article  PubMed  CAS  Google Scholar 

  71. Porter JM, Cutler BS, Lee BY, et al. 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 1982; 104: 66–72

    Article  PubMed  CAS  Google Scholar 

  72. Lindgarde F, Labs KH, Rossner M. The pentoxifylline experience: exercise testing reconsidered. Vasc Med 1996; 1: 145–54

    PubMed  CAS  Google Scholar 

  73. Lindgarde F, Jelnes R, Bjorkman H, et al. Conservative drug treatment in patients with moderately severe chronic occlusive peripheral arterial disease: Scandinavian Study Group. Circulation 1989; 80: 1549–56

    Article  PubMed  CAS  Google Scholar 

  74. Dawson DL, Cutler BS, Hiatt WR, et al. A comparison of cilostazol and pentoxifylline for treating intermittent claudication. Am J Med 2000; 109: 523–30

    Article  PubMed  CAS  Google Scholar 

  75. Hood SC, Moher D, Barber GG. Management of intermittent claudication with pentoxifylline: meta-analysis of randomized controlled trials. CMAJ 1996; 155: 1053–9

    PubMed  CAS  Google Scholar 

  76. Girolami B, Bernardi E, Prins MH, et al. Treatment of intermittent claudication with physical training, smoking cessation, pentoxifylline, or nafronyl: a meta-analysis. Arch Intern Med 1999; 159: 337–45

    Article  PubMed  CAS  Google Scholar 

  77. Kohda N, Tani T, Nakayma S, et al. Effect of cilostazol, a phosphodiesterase III inhibitor, on experimental thrombosis in the porcine carotid artery. Thromb Res 1999; 96: 261–8

    Article  PubMed  CAS  Google Scholar 

  78. Igawa T, Tani T, Chijiwa T, et al. Potentiation of anti-platelet aggregating activity of cilostazol with vascular endothelial cells. Thromb Res 1990; 57: 617–23

    Article  PubMed  CAS  Google Scholar 

  79. Tsuchikane E, Fukuhara A, Kobayashi T, et al. Impact of cilostazol on restenosis after percutaneous coronary balloon angioplasty. Circulation 1999; 100: 21–6

    Article  PubMed  CAS  Google Scholar 

  80. Coffman JD. Vasodilator drugs in peripheral vascular disease. N Engl J Med 1979; 300: 713–7

    Article  PubMed  CAS  Google Scholar 

  81. Money SR, Herd JA, Isaacsohn JL, et al. Effect of cilostazol on walking distances in patients with intermittent claudication caused by peripheral vascular disease. J Vasc Surg 1998; 27: 267–74

    Article  PubMed  CAS  Google Scholar 

  82. Dawson DL, Culter BS, Meissner MH, et al. Cilostazol has beneficial effects in the treatment of intermittent claudication: results from a multicenter, randomized, prospective, double-blinded trail. Circulation 1998; 98: 678–86

    Article  PubMed  CAS  Google Scholar 

  83. Beebe HG, Dawson DL, Cutler BS, et al. A new pharmacological treatment for intermittent claudication: results of a randomized, multicenter trial. Arch Intern Med 1999; 159: 2041–50

    Article  PubMed  CAS  Google Scholar 

  84. Packer M, Carver JR, Rodheffer RJ, et al. Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med 1991; 325: 1468–75

    Article  PubMed  CAS  Google Scholar 

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  1. Cardiology Section, Department of Veterans Affairs, Medical Service, Malcom Randall VA Medical Center, Gainesville, Florida, USA

    Chin K. Kim, Carsten M. Schmalfuss, Richard S. Schofield &  David S. Sheps

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Kim, C.K., Schmalfuss, C.M., Schofield, R.S. et al. Pharmacological Treatment of Patients with Peripheral Arterial Disease. Drugs 63, 637–647 (2003). https://doi.org/10.2165/00003495-200363070-00002

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