Medical treatment of peripheral arterial disease and claudication

New England Journal of Medicine

Volumn 344, Issue 21, 2001, Pages 1608-1621

  Hiatt, William R ^a,b  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^b Colorado Prevention Center ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; ALPHA TOCOPHEROL; ANTILIPEMIC AGENT; ANTITHROMBOCYTIC AGENT; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CARNITINE; CHOLESTEROL; CILOSTAZOL; CLOFIBRATE; CLOPIDOGREL; COLESTYRAMINE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; HOMOCYSTEINE; INSULIN; KETANSERIN; LIPOPROTEIN A; NAFTIDROFURYL; NICOTINIC ACID; PENTOXIFYLLINE; PICOTAMIDE; PROBUCOL; PROPIONYLCARNITINE; PROSTAGLANDIN; SIMVASTATIN; SULFONYLUREA DERIVATIVE; TESTOSTERONE; TICLOPIDINE; VASODILATOR AGENT;

AGE; ARTERY DISEASE; ATHEROSCLEROSIS; CLAUDICATION; CLINICAL TRIAL; DIABETES MELLITUS; DIET THERAPY; DRUG EFFICACY; HEART INFARCTION; HUMAN; HYPERLIPIDEMIA; HYPERTENSION; ISCHEMIC HEART DISEASE; KINESIOTHERAPY; LEG ISCHEMIA; PRIORITY JOURNAL; QUALITY OF LIFE; REVIEW; RISK FACTOR; SMOKING; STROKE; WALKING;

ALGORITHMS; DIABETES MELLITUS; ESTROGENS; EXERCISE THERAPY; HUMANS; HYPERLIPIDEMIAS; HYPERTENSION; INTERMITTENT CLAUDICATION; PERIPHERAL VASCULAR DISEASES; PLATELET AGGREGATION INHIBITORS; RISK FACTORS; SMOKING CESSATION; VASODILATOR AGENTS;

EID: 0035942767     PISSN: 00284793     EISSN: None     Source Type: Journal    
DOI: 10.1056/NEJM200105243442108     Document Type: Review

References (125)

1. Schroll M, Munck O. Estimation of peripheral arteriosclerotic disease by ankle blood pressure measurements in a population study of 60-year-old men and women. J Chronic Dis 1981;34:261-9.
2. Meijer WT, Hoes AW, Rutgers D, Bots ML, Hofman A, Grobbee DE. Peripheral arterial disease in the elderly: the Rotterdam Study. Arterioscler Thromb Vasc Biol 1998;18:185-92.
3. Fowkes FGR, Housley E, Cawood EHH, Macintyre CCA, Ruckley CV, Prescott RJ. Edinburgh Artery Study: prevalence of asymptomatic and symptomatic peripheral arterial disease in the general population. Int J Epidemiol 1991;20:384-92.
4. Newman AB, Sutton-Tyrrell K, Rutan GH, Locher J, Kuller LH. Lower extremity arterial disease in elderly subjects with systolic hypertension. J Clin Epidemiol 1991;44:15-20.
5. Newman AB, Siscovick DS, Manolio TA, et al. Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Circulation 1993;88:837-45.
6. Zheng ZJ, Sharrett AR, Chambless LE, et al. Associations of ankle-brachial index with clinical coronary heart disease, stroke and preclinical carotid and popliteal atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Study. Atherosclerosis 1997;131:115-25.
7. Criqui MH, Fronek A, Barrett-Connor E, Klauber MR, Gabriel S, Goodman D. The prevalence of peripheral arterial disease in a defined population. Circulation 1985;71:510-5.
8. 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.
9. 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: 381-6.
10. Vogt MT, Cauley JA, Newman AB, Kuller LH, Hulley SB. Decreased ankle/arm blood pressure index and mortality in elderly women. JAMA 1993;270:465-9.
11. Leng GC, Lee AJ, Fowkes FG, et al. Incidence, natural history and cardiovascular events in symptomatic and asymptomatic peripheral arterial disease in the general population. Int J Epidemiol 1996;25:1172-81.
12. Newman AB, Shemanski L, Manolio TA, et al. Ankle-arm index as a predictor of cardiovascular disease and mortality in the Cardiovascular Health Study. Arterioscler Thromb Vasc Biol 1999;19:538-45.
13. Newman AB, Tyrrell KS, Kuller LH. Mortality over four years in SHEP participants with a low ankle-arm index. J Am Geriatr Soc 1997;45: 1472-8.
14. Kornitzer M, Dramaix M, Sobolski J, Degre S, De Backer G. Ankle/ arm pressure index in asymptomatic middle-aged males: an independent predictor of ten year coronary heart disease mortality. Angiology 1995;46: 211-9.
15. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329-39.
16. Orchard TJ, Strandness DE. Assessment of peripheral vascular disease in diabetes: report and recommendations of an international workshop sponsored by the American Diabetes Association and the American Heart Association September 18-20, 1992, New Orleans, Louisiana. Circulation 1993;88:819-28.
17. McKenna M, Wolfson S, Kuller L. The ratio of ankle and arm arterial pressure as an independent predictor of mortality. Atherosclerosis 1991;87: 119-28.
18. Vogt MT, McKenna M, Anderson SJ, Wolfson SK, Kuller LH. The relationship between ankle-arm index and mortality in older men and women. J Am Geriatr Soc 1993;41:523-30.
19. Dormandy JA, Heeck L, Vig S. The fate of patients with critical leg ischemia. Semin Vasc Surg 1999;12:142-7.
20. Graham IM, Daly LE, Refsum HM, et al. Plasma homocysteine as a risk factor for vascular disease: the European Concerted Action Project. JAMA 1997;277:1775-81.
21. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA 1993;269:3015-23.
22. 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. [Erratum, Arch Intern Med 1998;158:573.]
23. McDermott MM, Mehta S, Ahn H, Greenland P. Atherosclerotic risk factors are less intensively treated in patients with peripheral arterial disease than in patients with coronary artery disease. J Gen Intern Med 1997;12: 209-15.
24. Clark AL, Byrne JC, Nasser A, McGroarty E, Kennedy JA. Cholesterol in peripheral vascular disease - a suitable case for treatment? QJM 1999;92:219-22.
25. Rose GA, Blackburn H. Cardiovascular survey methods. World Health Organization monograph series. No. 56. Geneva: World Health Organization, 1968.
26. Imparato AM, Kim GE, Davidson T, Crowley JG. Intermittent claudication: its natural course. Surgery 1975;78:795-9.
27. McDermott MM, Mehta S, Liu K, et al. Leg symptoms, the ankle-brachial index, and walking ability in patients with peripheral arterial disease. J Gen Intern Med 1999;14:173-81.
28. Vogt MT, Cauley JA, Kuller LH, Nevitt MC. Functional status and mobility among elderly women with lower extremity arterial disease: the Study of Osteoporotic Fractures. J Am Geriatr Soc 1994;42:923-9.
29. Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). J Vasc Surg 2000;31:S1-S296.
30. Quick CRG, Cotton LT. The measured effect of stopping smoking on intermittent claudication. Br J Surg 1982;69:Suppl:S24-S26.
31. 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.
32. Jorenby DE, Leischow SJ, Nides MA, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 1999;340:685-91.
33. LaRosa JC, He J, Vupputuri S. Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials. JAMA 1999;282: 2340-6.
34. Khan F, Litchfield SJ, Belch JJ. Cutaneous microvascular responses are improved after cholesterol-lowering in patients with peripheral arterial disease and hypercholesterolaemia. Adv Exp Med Biol 1997;428:49-54.
35. Kirk G, McLaren M, Muir AH, Stonebridge PA, Belch JJ. Decrease in P-selectin levels in patients with hypercholesterolaemia and peripheral arterial occlusive disease after lipid-lowering treatment. Vasc Med 1999;4:23-6.
36. Leng GC, Price JF, Jepson RG. Lipid-lowering for lower limb atherosclerosis (Cochrane review). In: The Cochrane library. Oxford, England: Update Software, 2001.
37. Blankenhorn DH, Azen SP, Crawford DW, et al. Effects of colestipolniacin therapy on human femoral atherosclerosis. Circulation 1991;83:438-47.
38. Lewis B. Randomised controlled trial of the treatment of hyperlipidaemia on progression of atherosclerosis. Acta Med Scand Suppl 1985;701: 53-7.
39. Walldius G, Erikson U, Olsson AG, et al. The effect of probucol on remoral atherosclerosis: the Probucol Quantitative Regression Swedish Trial (PQRST). Am J Cardiol 1994;74:875-83.
40. Kroon AA, van Asten WN, Stalenhoef AF. Effect of apheresis of low-density lipoprotein on peripheral vascular disease in hypercholesterolemic patients with coronary artery disease. Ann Intern Med 1996;125:945-54.
41. Buchwald H, Bourdages HR, Campos CT, Nguyen P, Williams SE, Boen JR. Impact of cholesterol reduction on peripheral arterial disease in the Program on the Surgical Control of the Hyperlipidemias (POSCH). Surgery 1996;120:672-9.
42. 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.
43. Ansell BJ, Watson KE, Fogelman AM. An evidence-based assessment of NCEP Adult Treatment Panel II guidelines: National Cholesterol Education Program. JAMA 1999;282:2051-7.
44. 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.
45. Effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control and Complications Trial. Am J Cardiol 1995;75:894-903.
46. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837-53. [Erratum, Lancet 1999;354:602.]
47. Frohlich ED, Tarazi RC, Dustan HP. Peripheral arterial insufficiency: a complication of beta-adrenergic blocking therapy. JAMA 1969;208:2471-2.
48. Solomon SA, Ramsay LE, Yeo WW, Parnell L, Morris-Jones W. Beta blockade and intermittent claudication: placebo controlled trial of atenolol and nifedipine and their combination. BMJ 1991;303:1100-4.
49. Hiatt WR, Stoll S, Nies AS. Effect of B-adrenergic blockers on the peripheral circulation in patients with peripheral vascular disease. Circulation 1985;72:1226-31.
50. Radack K, Deck C. Beta-adrenergic blocker therapy does not worsen intermittent claudication in subjects with peripheral arterial disease: a metaanalysis of randomized controlled trials. Arch Intern Med 1991;151:1769-76.
51. Heintzen MP, Strauer BE. Peripheral vascular effects of beta-blockers. Eur Heart J 1994;15:Suppl C:2-7.
52. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting - enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000;342:145-53. [Errata, N Engl J Med 2000;342:748, 1376.]
53. Welch GN, Loscalzo J. Homocysteine and atherothrombosis. N Engl J Med 1998;338:1042-50.
54. Jacques PF, Selhub J, Bostom AG, Wilson PWF, Rosenberg IH. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med 1999;340:1449-54.
55. Westendorp IC, in't Veld BA, Grobbee DE, et al. Hormone replacement therapy and peripheral arterial disease: the Rotterdam study. Arch Intern Med 2000;160:2498-502.
56. Hsia J, Simon JA, Lin F, et al. Peripheral arterial disease in randomized trial of estrogen with progestin in women with coronary heart disease: the Heart and Estrogen/Progestin Replacement Study. Circulation 2000;102: 2228-32.
57. Timaran CH, Stevens SL, Grandas OH, Piercy KT, Freeman MB, Goldman MH. Influence of hormone replacement therapy on graft patency after femoropopliteal bypass grafting. J Vasc Surg 2000;32:506-18.
58. Collaborative overview of randomised 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. [Erratum, BMJ 1994;308:1540.]
59. Sachdev GP, Ohlrogge KD, Johnson CL. Review of the Fifth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy: outpatient management for adults. Am J Health Syst Pharm 1999;56:1505-14.
60. Food and Drug Administration. Internal analgesic, antipyretic, and antirheumatic drug products for over-the-counter human use: final rule for professional labeling of aspirin, buffered aspirin, and aspirin in combination with antacid drug products. Fed Regist 1998;63(205):56802-19.
61. Goldhaber SZ, Manson JE, Stampfer MJ, et al. Low-dose aspirin and subsequent peripheral arterial surgery in the Physicians' Health Study. Lancet 1992;340:143-5.
62. Collaborative overview of randomised trials of antiplatelet therapy. II. Maintenance of vascular graft or arterial patency by antiplatelet therapy. BMJ 1994;308:159-68.
63. Janzon L, Bergqvist D, Boberg J, et al. Prevention of myocardial infarction and stroke in patients with intermittent claudication: effects of ticlopidine: results from STIMS, the Swedish Ticlopidine Multicenter Study. J Intern Med 1990;227:301-8. [Erratum, J Intern Med 1990;228:659.]
64. 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.
65. Bergqvist D, Almgren B, Dickinson JP. Reduction of requirement for leg vascular surgery during long-term treatment of claudicant patients with ticlopidine: results from the Swedish Ticlopidine Multicentre Study (STIMS). Eur J Vasc Endovasc Surg 1995;10:69-76.
66. Bennett CL, Weinberg PD, Rozenberg-Ben-Dror K, Yarnold PR, Kwaan HC, Green D. Thrombotic thrombocytopenic purpura associated with ticlopidine: a review of 60 cases. Ann Intern Med 1998;128:541-4.
67. Hankey GJ, Sudlow CL, Dunbabin DW. Thicnopyridine derivatives (ticlopidine, clopidogrel) versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients. Cochrane Database Syst Rev 2000;2:CD001246.
68. Bennett CL, Connors JM, Carwile JM, et al. Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med 2000;342: 1773-7.
69. Balsano F, Violi F. Effect of picotamide on the clinical progression of peripheral vascular disease: a double-blind placebo-controlled study. Circulation 1993;87:1563-9.
70. Prevention of atherosclerotic complications: controlled trial of ketanserin. BMJ 1989;298:424-30. [Erratum, BMJ 1989;298:644.]
71. Randomized placebo-controlled, double-blind trial of ketanserin in claudicants: changes in claudication distance and ankle systolic pressure: PACK Claudication Substudy. Circulation 1989;89:1544-8.
72. Hiatt WR, Nawaz D, Brass EP. Carnitine metabolism during exercise in patients with peripheral vascular disease. J Appl Physiol 1987;62:2383-7.
73. Khaira HS, Hanger R, Shearman CP. Quality of life in patients with intermittent claudication. Eur J Vasc Endovasc Surg 1996;11:65-9.
74. Nehler MR, Hiatt WR. Exercise therapy for claudication. Ann Vasc Surg 1999;13:109-14.
75. Regensteiner JG, Steiner JF, Hiatt WR. Exercise training improves functional status in patients with peripheral arterial disease. J Vasc Surg 1996;23:104-15.
76. Lundgren F, Dahllof A, Lundholm K, Schersten T, Volkmann R. Intermittent claudication - surgical reconstruction or physical training? A prospective randomized trial of treatment efficiency. Ann Surg 1989;209: 346-55.
77. Creasy TS, McMillan PJ, Fletcher EWL, Collin J, Morris PJ. Is percutaneous transluminal angioplasty better than exercise for claudication? Preliminary results from a prospective randomised trial. Eur J Vasc Surg 1990; 4:135-40.
78. Regensteiner JG, Meyer TJ, Krupski WC, Cranford LS, Hiatt WR. Hospital vs home-based exercise rehabilitation for patients with peripheral arterial occlusive disease. Angiology 1997;48:291-300.
79. Hiatt WR, Regensteiner JG, Hargarten ME, Wolfel EE, Brass EP. Benefit of exercise conditioning for patients with peripheral arterial disease. Circulation 1990;81:602-9.
80. Zetterquist S. The effect of active training on the nutritive blood flow in exercising ischemic legs. Scand J Clin Lab Invest 1970;25:101-11.
81. Hiatt WR, Regensteiner JG, Wolfel EE, Carry MR, Brass EP. Effect of exercise training on skeletal muscle histology and metabolism in peripheral arterial disease. J Appl Physiol 1996;81:780-8.
82. Hiatt WR, Wolfel EE, Meier RH, Regensteiner JG. Superiority of treadmill walking exercise versus strength training for patients with peripheral arterial disease: implications for the mechanism of the training response. Circulation 1994;90:1866-74.
83. Coffman JD. Vasodilator drugs in peripheral vascular disease. N Engl J Med 1979;300:713-7.
84. Samlaska CP, Winfield EA. Pentoxifylline. J Am Acad Dermatol 1994; 30:603-21.
85. 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.
86. Lindgarde F, Jelnes R, Bjorkman H, et al. Conservative drug treatment in patients with moderately severe chronic occlusive peripheral arterial disease. Circulation 1989;80:1549-56.
87. 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.
88. Hood SC, Moher D, Barber GG. Management of intermittent claudication with pentoxifylline: meta-analysis of randomized controlled trials. CMAJ 1996;155:1053-9.
89. Dawson DL, Cutler BS, Meissner MH, Strandness DEJ. Cilostazol has beneficial effects in treatment of intermittent claudication: results from a multicenter, randomized, prospective, double-blind trial. Circulation 1998; 98:678-86.
90. 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.
91. 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.
92. Moody AP, al-Khaffaf HS, Lehert P, Harris PL, Charlesworth D. An evaluation of patients with severe intermittent claudication and the effect of treatment with naftidrofuryl. J Cardiovasc Pharmacol 1994;23:Suppl 3: S44-S47.
93. Trubestein G, Bohme H, Heidrich H, et al. Naftidrofuryl in chronic arterial disease: results of a controlled multicenter study. Angiology 1984; 35:701-8.
94. Adhoute G, Andreassian B, Boccalon H, et al. Treatment of stage II chronic arterial disease of the lower limbs with the serotonergic antagonist naftidrofuryl: results after 6 months of a controlled, multicenter study. J Cardiovasc Pharmacol 1990;16:Suppl 3:S75-S80.
95. Brevetti G, Perna S, Sabba C, Martone VD, Condorelli M. Propionyl-L-carnitine in intermittent claudication: double-blind, placebo-controlled, dose titration, multicenter study. J Am Coll Cardiol 1995;26:1411-6.
96. Brevetti G, Diehm C, Lambert D. European multicenter study on propionyl-L-carnitine in intermittent claudication. J Am Coll Cardiol 1999;34:1618-24.
97. 1 prodrug, in patients with intermittent claudication. Circulation 1997;95:2298-302.
98. Diehm C, Balzer K, Bisler H, et al. Efficacy of a new prostaglandin E1 regimen in outpatients with severe intermittent claudication: results of a multicenter placebo-controlled double-blind trial. J Vasc Surg 1997;25: 537-44.
99. Lievre M, Azoulay S, Lion L, Morand S, Girre JP, Boissel JP. A dose-effect study of beraprost sodium in intermittent claudication. J Cardiovasc Pharmacol 1996;27:788-93.
100. Lievre M, Morand S, Besse B, Fiessinger JN, Boissel JP. Oral beraprost sodium, a prostaglandin I(2) analogue, for intermittent claudication: a double-blind, randomized, multicenter controlled trial. Circulation 2000;102:426-31.
101. Ernst E. Pentoxifylline for intermittent claudication: a critical review. Angiology 1994;45:339-45.
102. Radack K, Wyderski RJ. Conservative management of intermittent claudication. Ann Intern Med 1990;113:135-46.
103. Abbas R, Chow CP, Browder NJ, et al. In vitro metabolism and interaction of cilostazol with human hepatic cytochrome P450 isoforms. Hum Exp Toxicol 2000;19:178-84.
104. Kohda N, Tani T, Nakayama S, et al. Effect of cilostazol, a phosphodiesterase III inhibitor, on experimental thrombosis in the porcine carotid artery. Thromb Res 1999;96:261-8.
105. 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.
106. Tsuchikane E, Fukuhara A, Kobayashi T, et al. Impact of cilostazol on restenosis after percutaneous coronary balloon angioplasty. Circulation 1999;100:21-6.
107. Packer M, Carver JR, Rodeheffer RJ, et al. Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med 1991;325:1468-75.
108. Cone J, Wang S, Tandon N, et al. Comparison of the effects of cilostazol and milrinone on intracellular cAMP levels and cellular function in platelets and cardiac cells. J Cardiovasc Pharmacol 1999;34:497-504.
109. Lehert P, Comte S, Gamand S, Brown TM. Naftidrofuryl in intermittent claudication: a retrospective analysis. J Cardiovasc Pharmacol 1994; 23:Suppl 3:S48-S52.
110. Brass EP, Hiatt WR. Acquired skeletal muscle metabolic myopathy in atherosclerotic peripheral arterial disease. Vasc Med 2000;5:55-9.
111. Brass EP, Hiatt WR, Gardner AW, Hoppel CL. Decreased NADH dehydrogenase and ubiquinol-cytochrome c oxidoreductase in peripheral arterial disease. Am J Physiol Heart Circ Physiol 2001;280:H603-H609.
112. Hiatt WR, Wolfel EE, Regensteiner JG, Brass EP. Skeletal muscle carnitine metabolism in patients with unilateral peripheral arterial disease. J Appl Physiol 1992;73:346-53.
113. Brevetti G, Perna S, Sabba C, et al. Superiority of L-propionylcarnitine vs L-carnitine in improving walking capacity in patients with peripheral vascular disease: an acute, intravenous, double-blind, cross-over study. Eur Heart J 1992;13:251-5.
114. Norgren L, Alwmark A, Angqvist KA, et al. A stable prostacyclin analogue (iloprost) in the treatment of ischaemic ulcers of the lower limb: a Scandinavian-Polish placebo controlled, randomised multicenter study. Eur J Vasc Surg 1990;4:463-7.
115. U.K. Severe Limb Ischaemia Study Group. Treatment of limb threatening ischaemia with intravenous iloprost: a randomised double-blind placebo controlled study. Eur J Vasc Surg 1991;5:511-6.
116. Ernst E. Chelation therapy for peripheral arterial occlusive disease: a systematic review. Circulation 1997;96:1031-3.
117. Kleijen I, Mackerras D. Vitamin E for intermittent claudication (Cochrane review). In: The Cochrane library. Oxford, England: Update Software, 2001.
118. Price IF, Leng GC. Steroid sex hormones for lower limb atherosclerosis (Cochrane review). In: The Cochrane library. Oxford, England: Update Software, 2001.
119. Trubestein G, Balzer K, Bisler H, et al. Buflomedil in arterial occlusive disease: results of a controlled multicenter study. Angiology 1984;35: 500-5.
120. Peters H, Kieser M, Holscher U. Demonstration of the efficacy of ginkgo biloba special extract EGb 761 on intermittent claudication -a placebo-controlled, double-blind multicenter trial. Vasa 1998;27:106-10.
121. O'Hara J, Jolly PN, Nicol CG. The therapeutic efficacy of inositol nicotinate (Hexopal) in intermittent claudication: a controlled trial. Br J Clin Pract 1988;42:377-83.
122. Violi F, Marubini E, Coccheri S, Nenci GG. Improvement of walking distance by defibrotide in patients with intermittent claudication - results of a randomized, placebo-controlled study (the DICLIS study): Defibrotide Intermittent CLaudication Italian Study. Thromb Haemost 2000; 83:672-7.
123. Bagger JP, Helligsoe P, Randsbaek F, Kimose HH, Jensen BS. Effect of verapamil in intermittent claudication: a randomized, double blind, placebo-controlled, cross-over study after individual dose-response assessment. Circulation 1997;95:411-4.
124. Girolami B, Bernardi E, Prins MH, et al. Antithrombotic drugs in the primary medical management of intermittent claudication: a metaanalysis. Thromb Haemost 1999;81:715-22.
125. Boger RH, Bode-Boger SM, Thiele W, Cruetzig A, Alexander K, Frolich JC. Restoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease. J Am Coll Cardiol 1998;32:1336-44.