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Pharmacological Approaches to the Treatment of Intermittent Claudication

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  • Clinical Pharmacology
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Summary

Intermittent claudication is a common condition of the elderly, occurring in 3 to 20% of individuals over the age of 65 years. Although local disease is usually benign, life expectancy in patients with intermittent claudication is reduced by approximately 10 years due to associated cardiovascular mortality.

Several classes of drugs have been used in intermittent claudication, but clinical studies evaluating their efficacy leave much to be desired. Pentoxifylline (oxpentifylline), a rheological agent, and naftidrofuryl, an enhancer of aerobic metabolism, are the 2 most widely investigated and utilised drugs. The combined results of 10 placebo-controlled studies with pentoxifylline and 4 with naftidrofuryl estimate increases in claudication distances of 51 and 42%, respectively. How-† The views expressed in this article are those of the authors and should not be taken to represent the official view of the UK Medicines Control Agency. ever, due to publication bias, these figures are probably overestimates of the true benefit from treatment with these drugs. It is likely that any benefit from pentoxifylline or naftidrofuryl is small and of little clinical importance. The suggestion that naftidrofuryl has greater efficacy in older patients remains unproven. Other classes of drugs including vasodilators, antiplatelet drugs, anticoagulants and prostaglandins have not been shown to be effective.

Only 2 approaches to the management of intermittent claudication have been shown convincingly to be of benefit: stopping smoking and exercising regularly.

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References

  • Arcan JC, Blanchard J, Boissel JP, Destors JM, Panak E. Multicenter double-blind study of ticlopidine in the treatment of intermittent claudication and the prevention of its complications. Angiology 39: 802–811, 1988

    Article  PubMed  CAS  Google Scholar 

  • Adhoute G, Bacourt F, Barral M, Cardon JM, Chevalier JM, et al. Naftidrofuryl in chronic arterial disease: results of a six month controlled multicenter study using Naftidrofuryl tablets 200mg. Angiology 37: 160–167, 1986

    Article  PubMed  CAS  Google Scholar 

  • Andriessen MP, Barendsen GJ, Wonda AA, de Pater L. Changes of walking distance in patients with intermittent claudication during six months intensive physical training. Vasa 18(1): 63–68, 1989

    PubMed  CAS  Google Scholar 

  • Antiplatelet Trialists’ Collaboration. Secondary prevention of vascular disease by prolonged antiplatelet treatment. British Medical Journal 296: 320–331, 1988

    Article  Google Scholar 

  • Balsano F, Coccheri S, Libretti A, Nenci GG, Catalano M, et al. Ticlopidine in the treatment of intermittent claudication: a 21-month double-blind trial. Journal of Laboratory and Clinical Medicine 114: 84–91, 1989

    PubMed  CAS  Google Scholar 

  • Blombery PA. Intermittent claudication: an update on management. Drugs 34: 404–410, 1987

    Article  PubMed  CAS  Google Scholar 

  • Boissel JP, Peyrieux JC, Destors JM. Is it possible to reduce the risk of cardiovascular events in subjects suffering from intermittent claudication of the lower limbs? Thrombosis and Haemostasis 62: 681–685, 1989

    PubMed  CAS  Google Scholar 

  • Bollinger A, Frei C. Double-blind study of pentoxifylline against cardiovascular events in subjects suffering from intermittent claudication. Pharmatherapeutica 1: 557–562, 1977

    Google Scholar 

  • Boobis LH, Bell PRF. Can drugs help patients with lower limb ischaemia? British Journal of Surgery 69 (Suppl.): 17–23, 1982

    Article  Google Scholar 

  • Bounameaux H, Holditch T, Hellemans H, Berent A, Verhaeghe R. Placebo-controlled, double-blind, two-centre trial of ketanserin in intermittent claudication. Lancet 2: 1268–1271, 1985

    Article  PubMed  CAS  Google Scholar 

  • Brown WGK, Baird RJ. Vasodilating drugs in peripheral vascular disease. Canadian Medical Association Journal 93: 219–224, 1965

    PubMed  CAS  Google Scholar 

  • Cameron HA, Waller PC, Ramsay LE. Placebo-controlled trial of ketanserin in the treatment of intermittent claudication. Angiology 38: 549–555, 1987

    Article  PubMed  CAS  Google Scholar 

  • Cameron HA, Waller PC, Ramsay LE. Drug treatment of intermittent claudication: a critical analysis of the methods and findings of published clinic trials, 1965–1985. British Journal of Clinical Pharmacology 26: 569–576, 1988

    Article  PubMed  CAS  Google Scholar 

  • Campbell WB. Angioplasty for intermittent claudication. British Medical Journal 293: 1047–1048, 1986

    Article  PubMed  CAS  Google Scholar 

  • Chopra HK, Chopra KL, Aggarwal KK, Parashar SK. Pentoxifylline (Trental): a new drug for the treatment of peripheral chronic occlusive arterial disease. Journal of Medicine 19(2): 89–107, 1988

    PubMed  CAS  Google Scholar 

  • Clement DL, Duprez D. Effect of ketanserin in the treatment of patients with intermittent claudication: results from 13 placebo-controlled parallel group studies. Journal of Cardiovascular Pharmacology 10(Suppl. 3): 89–95, 1987

    Google Scholar 

  • Clyne CAC, Galland RB, Fox MJ, Gustave R, Jantet GH, et al. A controlled trial of naftidrofuryl (Praxilene) in the treatment of intermittent claudication. British Journal of Surgery 67: 347–348, 1980

    Article  PubMed  CAS  Google Scholar 

  • Coffman JD, Intermittent claudication: not so benign. American Heart Journal 112(5): 1127–1128, 1986

    Article  PubMed  CAS  Google Scholar 

  • Coffman JD. New drug therapy in peripheral vascular disease. Medical Clinics of North America 72(1): 259–265, 1988

    PubMed  CAS  Google Scholar 

  • Criqui MH, Fronek A, Klauber MR, Barrett-Connor E, Gabriel S. The sensitivity, specificity, and predictive value of traditional clinical evaluation of peripheral arterial disease: results from non-invasive testing in a defined population. Circulation 71: 516–522, 1985

    Article  PubMed  CAS  Google Scholar 

  • DeCree J, Leempoels J, Geukens H, Verhaegen H. Placebo-controlled double-blind trial of ketanserin in treatment of intermittent claudication. Lancet 2: 775–779, 1984

    Article  CAS  Google Scholar 

  • DiPerri T, Geurrini M. Placebo-controlled double-blind study with pentoxifylline of walking performance in patients with intermittent claudication. Angiology 34: 40–45, 1983

    Article  CAS  Google Scholar 

  • Donaldson DR, Hall TJ, Rester RC, Ramsden CW, Wiggins PA. Does oxpentifylline have a place in the treatment of intermittent claudication? Current Medical Research and Opinion 9: 35–40, 1984

    Article  PubMed  CAS  Google Scholar 

  • Dormandy JA, Hoare E, Colley J, Arrowsmith DE, Dormandy TL. Clinic, haemodynamic, Theological and biochemical findings in 126 patients with intermittent claudication. British Medical Journal 4: 576–581, 1973

    Article  PubMed  CAS  Google Scholar 

  • Drug and Therapeutics Bulletin. Peripheral vascular disease: cinnarizine et al. 19: 27–28, 1981

    Google Scholar 

  • Drug and Therapeutics Bulletin. Naftidrofuryl (Praxilene). 26: 25–27, 1988

    Google Scholar 

  • Drug and Therapeutics Bulletin. Do drugs help intermittent claudication? 28: 1–2, 1990

    Google Scholar 

  • Editorial. Ticlopidine. Lancet 337: 459–460, 1991

  • Elkeles RS, Hampton JR, Harrison MJG, Mitchell JRA. Prostaglandin E1 and human platelets. Lancet 2: 111, 1969

    Article  PubMed  CAS  Google Scholar 

  • Emmons PR, Hampton JR, Harrison MJG, Honour AJ, Mitchell JRA. Effect of prostaglandin E1 on platelet behaviour in vitro and in vivo. British Medical Journal 2: 468–472, 1967

    Article  PubMed  CAS  Google Scholar 

  • Ernst E, Matrai A, Kollar L. Placebo-controlled double-blind study of haemodilution in peripheral arterial disease. Lancet 1: 1449–1451, 1987

    Article  PubMed  CAS  Google Scholar 

  • Evans JG. Intermittent claudication. Age and Ageing 17: 139, 1988

    Article  PubMed  CAS  Google Scholar 

  • Fiessinger JN, Schafer M. Trial of iloprost versus aspirin treatment for critical limb ischaemia of thromboangiitis obliterans. Lancet 335: 555–557, 1990

    Article  PubMed  CAS  Google Scholar 

  • Friedman SG, Kerner BA, Friedman MS, Moccio CG. Limb salvage in elderly patients. Is aggressive surgical therapy warranted? Journal of Cardiovascular Surgery 30(5): 848–851, 1989

    PubMed  CAS  Google Scholar 

  • Gallus AS, Morley AA, Gleadow F, Wenzel A, Dupont P, et al. Intermittent claudication: a double-blind crossover trial of pentoxifylline. Australia and New Zealand Journal of Medicine 15: 402–409, 1985

    Article  CAS  Google Scholar 

  • Gillespie JA. The case against vasodilator drugs in occlusive vascular disease of the legs. Lancet 2: 995–997, 1959

    Article  PubMed  CAS  Google Scholar 

  • Grigoleit HG, Porsche E, Stefanovich V, Jacobi G, Lahham A. The effect of pentoxifylline on red cell flexibility in healthy subjects after administration of Trental 400. Pharmatherapeutica 1(4): 241–247, 1976

    Google Scholar 

  • Hale WE, Marks RG, May FE, Moore MT, Stewart RB. Epidemiology of intermittent claudication: evaluation of risk factors. Age and Ageing 17: 57–60, 1988

    Article  PubMed  CAS  Google Scholar 

  • Hay CRM, Waller PC, Carter C, Cameron HA, Parnell L, et al. Lack of effect of a 24-hour infusion of iloprost in intermittent claudication. Thrombosis Research 46: 317–324, 1987

    Article  PubMed  CAS  Google Scholar 

  • Housley E. Treating claudication in five words. British Medical Journal 296: 1483–1484, 1988

    Article  PubMed  CAS  Google Scholar 

  • Janzon L, Bergqvist D, Boberg J, Boberg M, Eriksson I, et al. Prevention of myocardial infarction and stroke in patients with intermittent claudication; effects of ticlopidine. Results from STIMS, the Swedish Ticlopidine Multicentre Study. Journal of Internal Medicine 227: 301–308, 1990

    Article  PubMed  CAS  Google Scholar 

  • Johnson RH, Walton JL, Krebs HA, Williamson DH. Metabolic fuels during and after severe exercise in athletes and nonathletes. Lancet 2: 452–455, 1969

    Article  PubMed  CAS  Google Scholar 

  • Jonason T, Bergstrom R. Cessation of smoking in patients with intermittent claudication: effects on the risk of peripheral vascular complications, myocardial infarction and mortality. Acta Medica Scandinavica 221(3): 253–260, 1987

    Article  PubMed  CAS  Google Scholar 

  • Jonason T, Jonzon B, Ringquist I, Oman-Rydberg A. Effects of physical training on different categories of patients with intermittent claudication. Acta Medica Scandinavica 206: 253–258, 1979

    Article  PubMed  CAS  Google Scholar 

  • Kannel WB, McGee DL. Update on some epidemiologic features of intermittent claudication: the Framingham Study. Journal of the American Geriatric Society 33: 13–18, 1985

    CAS  Google Scholar 

  • Karnik R, Valentin A, Stollberger C, Slany J. Effects of naftidrofuryl in patients with intermittent claudication. Angiology 39: 234–240, 1988

    Article  PubMed  CAS  Google Scholar 

  • Kaukinen S, Ylitalo P, Pessi T, Vapaatalo H. Hemodynamic effects of Iloprost, a prostacyclin analogue. Clinical Pharmacology and Therapeutics 36: 464–469, 1984

    Article  PubMed  CAS  Google Scholar 

  • Laporte JR, Capella D. Useless drugs are not placebos: lessons from flunarizine and cinnarizine. Lancet 2: 853–854, 1986

    Article  PubMed  CAS  Google Scholar 

  • Larsen OA, Lassen NA. Effect of daily muscular exercise in patients with intermittent claudication. Lancet 2: 1093–1096, 1966

    Article  PubMed  CAS  Google Scholar 

  • Libretti A, Catalano M. Treatment of claudication with dipyridamole and aspirin. International Journal of Clinical Pharmacology Research 6: 59–60, 1986

    PubMed  CAS  Google Scholar 

  • Lindegarde F, Jelnes R, Bjorkman H, Adielsson G, Kjellstrom T, et al. Conservative drug treatment in patients with moderately severe chronic occlusive peripheral arterial disease. Scandinavian Study Group. Circulation 80(6): 1549–1556, 1989

    Article  Google Scholar 

  • McTavish D, Faulds D, Goa KL. Ticlopidine: an updated review of its pharmacology and therapeutic use in platelet-dependent disorders. Drugs 40: 238–259, 1990

    Article  PubMed  CAS  Google Scholar 

  • Meynaud A, Grand M, Fontaine L. Effet du naftidrofuryl sur le metabolisme energetique cerebral. Arzneimittel-Forschung 23(10): 1431–1436, 1973

    PubMed  CAS  Google Scholar 

  • Mitchell JRA. Prostaglandins in vascular disease: a seminal approach. British Medical Journal 282: 590–594, 1981

    Article  PubMed  CAS  Google Scholar 

  • Muller-Buhl U, Diehm C, Krais T, Zimmermann R, Morl H, et al. Clinical effects of intravenous Iloprost in patients with intermittent claudication. European Journal of Clinical Pharmacology 33: 127–131, 1987

    Article  PubMed  CAS  Google Scholar 

  • Orme M. Aspirin all round? British Medical Journal 296: 307–308, 1988

    Article  PubMed  CAS  Google Scholar 

  • PACK Claudication Substudy. Randomized placebo-controlled double-blind trial of ketanserin in claudicants: changes in claudication distance and ankle systolic pressure. Circulation 80(6): 1544–1548, 1989

    Article  Google Scholar 

  • PACK Trial Group. Prevention of atherosclerotic complications: controlled trial of ketanserin. British Medical Journal 298: 424–430, 1989

    Article  Google Scholar 

  • Porter JM, Cutler BS, Lee BY, Reich T, Reichle FA, et al. Pentoxifylline efficacy in the treatment of intermittent claudication: multicentre controlled double-blind trial with objective assessment of chronic occlusive arterial disease patients. American Heart Journal 104: 66–72, 1982

    Article  PubMed  CAS  Google Scholar 

  • Quick CRG, Cotton LT. The measured effect of stopping smoking on intermittent claudication. British Journal of Surgery 69 (Suppl.): 24–26, 1982

    Article  Google Scholar 

  • Roberts DH, Jsao Y, McLoughlin GA, Breckenridge A. Placebo-controlled comparison of captopril, atenolol, labetalol and pindolol in hypertension complicated by intermittent claudication. Lancet 2: 650–653, 1987

    Article  PubMed  CAS  Google Scholar 

  • Roekaerts F, Deleers L. Trental 400 in the treatment of intermittent claudication: results of long-term, placebo-controlled administration. Angiology 35: 396–406, 1984

    Article  PubMed  CAS  Google Scholar 

  • Ruckley CV, Callam MJ, Ferrington CM, Prescott RJ. Naftidrofuryl for intermittent claudication: a double-blind controlled trial. British Medical Journal 1: 622, 1978

    Article  PubMed  CAS  Google Scholar 

  • Schubotz R, Muhlfellner O. The effect of pentoxifylline on erythrocyte deformability and on phosphastide fatty acid distribution in the erythrocyte membrane. Current Medical Research and Opinion 4(9): 609–617, 1977

    Article  PubMed  CAS  Google Scholar 

  • Shaw SWJ, Johnson RH. The effect of naftidrofuryl on the metabolic response to exercise in man. Acta Neurologica Scandinavica 52: 231–237, 1975

    Article  PubMed  CAS  Google Scholar 

  • Smigiel M, Davis DH. Pseudoclaudication: a review of etiology, diagnosis and treatment. Geriatric Clinics of North America 1(2): 373–380, 1985

    CAS  Google Scholar 

  • Smud R, Sermukslis B, Kartin D. Changes in blood viscosity induced by pentoxifylline. Pharmatherapeutica 1(4): 229–233, 1976

    Google Scholar 

  • Solomon SA, Ramsay LE, Yeo WW, Parnell L, Morris-Jones W. Beta-blockade and intermittent claudication: placebo-controlled comparison of atenolol and nifedipine and their combination. British Medical Journal 303: 1100–1104, 1991

    Article  PubMed  CAS  Google Scholar 

  • Spagnoli A, Tognoni G. Cerebroactive drugs: clinical pharmacology and therapeutic role in cerebrovascular disorders. Drugs 26: 44–69, 1983

    Article  PubMed  CAS  Google Scholar 

  • Strano A, Davi G, Avellone G, Novo S, Pinto A. Double-blind crossover study of the clinical efficacy and haemorrheological effects of pentoxifylline in patients with occlusive arterial disease of the lower limbs. Angiology 35: 459–466, 1984

    Article  PubMed  CAS  Google Scholar 

  • Trubestein G, Bohme H, Heidrich H, Heinrich F, Hirche H, et al. Naftidrofuryl in chronic arterial disease: results of a controlled multicenter study. Angiology 35: 701–708, 1984

    Article  PubMed  CAS  Google Scholar 

  • Verstraete M. Current therapy for intermittent claudication. Drugs 24: 240–247, 1982

    Article  PubMed  CAS  Google Scholar 

  • Waller PC, Solomon SA, Ramsay LE. The acute effects of cigarette smoking on treadmill exercise distances in patients with stable intermittent claudication. Angiology 40: 164–169, 1989

    Article  PubMed  CAS  Google Scholar 

  • Ward A, Clissold SP. Pentoxifylline: a review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy. Drugs 34: 50–97, 1987

    Article  PubMed  CAS  Google Scholar 

  • Waters KJ, Craxford AD, Chamberlain J. The effect of naftidrofuryl (Praxilene) on intermittent claudication. British Journal of Surgery 67: 349–351, 1980

    Article  PubMed  CAS  Google Scholar 

  • Widmer LK, Greensher A, Kannel WB. Occlusion of peripheral arteries: a study of 6,400 working subjects. Circulation 30: 836–842, 1964

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Western Infirmary, Glasgow Blood Pressure Clinic, Glasgow, Scotland

    E. G. Bevan

  2. Medicines Control Agency, Market Towers, 1 Nine Elms Lane, London, SW8 5NQ, England

    P. C. Waller

  3. Department of Therapeutics, Royal Hallamshire Hospital, Sheffield, England

    L. E. Ramsay

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  1. E. G. Bevan
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  2. P. C. Waller
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  3. L. E. Ramsay
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The views expressed in this article are those of the authors and should not be taken to represent the official view of the UK Medicines Control Agency.

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Bevan, E.G., Waller, P.C. & Ramsay, L.E. Pharmacological Approaches to the Treatment of Intermittent Claudication. Drugs & Aging 2, 125–136 (1992). https://doi.org/10.2165/00002512-199202020-00006

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