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ß-Adrenergic Blocker Therapy Does Not Worsen Intermittent Claudication in Subjects With Peripheral Arterial Disease: A Meta-analysis of Randomized Controlled Trials

ß-Adrenergic Blocker Therapy Does Not Worsen Intermittent Claudication in Subjects With... Abstract β-Adrenergic blockers have been considered relatively contraindicated in peripheral arterial disease because of the perceived risk that these drugs could worsen intermittent claudication. Therefore, we conducted a meta-analysis of available randomized controlled trials from the English-language literature to determine whether or not β-blockers exacerbate intermittent claudication. The primary focus of this analysis was the effect of β-blockers on exercise dura tion, measured as walking capacity or endurance time. Outcomes were pooled where appropriate. Of 11 eligible reports, six included 11 individual controlled treatment comparisons that provided data for an analysis of pain-free exercise capacity; no effect size was statistically significant. The pooled effect size for pain-free walking distance was -0.24 (95% confidence interval, -0.62 to 0.14), indicat ing no significant impairment of walking capacity compared with placebo. Only one study reported that certain β-blockers were associated with worsening of intermittent claudication. These results strongly suggest that β-blockers do not adversely affect walking capacity or symptoms of intermittent claudication in patients with mild to moderate peripheral arterial disease. In the absence of other con traindications, β-blockers can probably be used safely in such patients. (Arch Intern Med. 1991;151:1769-1776) References 1. Criqui MH, Fronek A, Barrett-Connor E, et al. The preva lence of peripheral arterial disease in a defined population . Circulation. 1985;71:510-515.Crossref 2. Lassila R, Lepantalo M, Lindfors O. Peripheral arterial disease: natural outcome . Acta Med Scand. 1986;220:295-301.Crossref 3. Kannel WB, Skinner JJ Jr, Schwartz MG, et al. Intermittent claudication: incidence in the Framingham Study . Circulation. 1970;41:875-883.Crossref 4. Kannel WB, McGee DL. Update on some epidemiologic features of intermittent claudication: the Framingham Study . J Am Geriatr Soc. 1985;33:13-18. 5. Hughson WG, Mann Jl, Garrod A. Intermittent claudication: prevalence and risk factors . BMJ. 1978;1:1379-1381.Crossref 6. Ramsay LE. Intermittent claudication in hypertensive men . J R Coll Phys Lond. 1979;13:100-102. 7. Sivertsson R, Andersson O, Hansson L. Blood pressure reduction in vascular adaption . Acta Med Scand. 1979;205:477-482.Crossref 8. George CF. Beta-receptor blocking agents . Prescribers J. 1974;14:93-98. 9. Frishman WH. Beta-adrenergic receptor blockers: ad verse effects and drug interactions . Hypertension. 1988;11( (suppl II) ):21-29.Crossref 10. Thulesius O. Beta-adrenergic blockade and vasospasm . Acta Med Scand. 1979;625( (suppl) ):41-43. 11. Lepantalo M. Beta blockade and intermittent claudica tion . Acta Med Scand. 1985;700( (suppl) ):1-48. 12. Breckenridge A. Which beta-blocker? BMJ. 1983;286:1085-1088.Crossref 13. Rodger JC, Sheldon CD, Lerski RA, Livingstone WR. In termittent claudication complicating beta-blockade . BMJ. 1976;1:1125.Crossref 14. Fogoros RN. Exacerbation of intermittent claudication by propranolol . N Engl J Med. 1980;302:1089. 15. Rodgers LD, Thieman KC, Mosier CL. Peripheral is chemia secondary to beta-blocker therapy . J lowa Med Soc. 1983;73:13-14. 16. Vale JA, Jefferys DB. Peripheral gangrene complicating beta-blockade . Lancet. 1978;1:1216.Crossref 17. Frohlich ED, Tarazi RC, Dustan HP. Peripheral arterial in sufficiency: a complication of beta-adrenergic blocking ther apy . JAMA. 1969;208:2471-2472.Crossref 18. Lepantalo M, Aromaa A, Klaukka T, Lukkari E. Does beta blockade provoke intermittent claudication? Acta Med Scand. 1985;218:35-39.Crossref 19. Lepantalo M, von Knorring J, Lindfors O, Scheinin TM. The effect of withdrawal of beta-adrenergic blockade on inter mittent claudication . Angiology. 1983;34:401-411.Crossref 20. Reichert N, Shibolet S, Adar R, Gafni J. Controlled trial of propranolol in intermittent claudication . Clin Pharmacol Ther. 1975;17:612-615. 21. Clement DL. Studies on the effect of alpha- and of beta-adrenergic blocking agents on the circulation in human limbs . Verh K Acad Geneeskd Belg. 1980;42:164-214. 22. Smith RS, Warren DJ. Effect of beta-blocking drugs on peripheral blood flow in intermittent claudication . J Cardiovasc Pharmacol. 1982;4:2-4.Crossref 23. Bogaert MG, Clement DL. Lack of influence of propra nolol and metoprolol on walking distance in patients with chronic intermittent claudication . Eur Heart J. 1983;4:203-204. 24. Lepantalo M, von Knorring J. Walking capacity of patients with intermittent claudication during chronic antihypertensive treatment with metoprolol and methyldopa . Clin Physiol. 1984;4:275-282.Crossref 25. Lepantalo M. Chronic effects of metoprolol and methyl dopa on calf blood flow in intermittent claudication . Br J Clin Pharmacol. 1984;18:90-93.Crossref 26. Hiatt WR, Stoll S, Nies AS. Effect of β-adrenergic block ers on the peripheral circulation in patients with peripheral vascular disease . Circulation. 1985;72:1226-1231.Crossref 27. Lepantalo M. Chronic effects of labetalol, pindolol, and propranolol on calf blood flow in intermittent claudication . Clin Pharmacol Ther. 1985;37:7-12.Crossref 28. Bostrom PA, Janzon L, Ohlsson O, Westergren A. The effect of beta-blockade on leg blood flow in hypertensive pa tients with intermittent claudication . Angiology. 1986;37:149-153.Crossref 29. Svendsen TL, Jelnes R, Tonnesen KH. The effects of acebutolol and metoprolol on walking distances and distal blood pressure in hypertensive patients with intermit tent claudication . Acta Med Scand. 1986;219:161-165.Crossref 30. Roberts DH, Tsao Y, McLoughlin GA, Breckenridge A. Placebo-controlled comparison of captopril, atenolol, labe talol, and pindolol in hypertension complicated by intermittent claudication . Lancet . 1987;1:650-653.Crossref 31. Sacks HS, Berrier J, Reitman D, et al. Meta-analysis of randomized controlled trials . N Engl J Med. 1987;316:450-455.Crossref 32. Chalmers TC, Smith H, Blackburn B, et al. A method for assessing the quality of a randomized controlled trial . Con trolled Clin Trials. 1981;2:31-49.Crossref 33. DerSimonian R, Charette LJ, McPeek B, Mosteller F. Re porting on methods in clinical trials . N Engl J Med. 1982;306:1332-1337.Crossref 34. Hedges LV, Olkin I. Statistical Methods for Meta-analysis. Orlando, Fla: Academic Press; 1985. 35. Lepantalo M, Totterman KJ. Effect of long-term betaadrenergic-blockade on calf blood flow in hypertensive pa tients . Clin Physiol. 1983;3:35-42.Crossref 36. Ingram DM, House AK, Thompson GH, Stacey MC, Castleden WM, Lovegrove FT. Beta-adrenergic blockade and peripheral vascular disease . Med J Aust. 1982;1:509-511. 37. McSorley PD, Warren DJ. Effects of propranolol and me toprolol on the peripheral circulation . BMJ. 1978;2:1598-1600.Crossref 38. Agerskov K. Effect of propranolol on the tone of collat eral arteries in patients with occlusion of the superficial femo ral artery . Clin Physiol. 1983;3:43-48.Crossref 39. Lepantalo M, Lindstrom BL, Totterman KJ. Adrenoceptor blocking drugs and cold feet in intermittent claudication . Vasa. 1986;15:135-137. 40. Vandenburg MJ. The acute and chronic effect on oxprenolol and propranolol on peripheral blood flow in hypertensive patients . Br J Clin Pharmacol. 1982;14:733-737.Crossref 41. Eliasson K, Lins LE, Sundqvist K. Peripheral vasospasm during beta-receptor blockade: a comparison between meto prolol and pindolol . Acta Med Scand. 1982;665:109-112. 42. Eliasson K, Lins LE, Sundqvist K. Vasospastic phenomena in patients treated with beta-adrenoceptor blocking agents . Acta Med Scand. 1978;628( (suppl) ):39-46. 43. Svendsen TL, Jelnes R, Tonnesen KH. Is adrenergic betareceptor blockade contraindicated in patients with intermittent claudication? Acta Med Scand. 1985;693( (suppl) ):129-132. 44. Cohen J. Statistical Power Analysis for the Behavioral Sciences . Hillsdale, NJ: Lawrence Erlbaum Assoc; 1988. 45. Yao JST, Needham TN, Gourmoos C, Irvine WT. A com parative study of strain-gauge plethysmography and Doppler ultrasound in the assessment of occlusive arterial disease of the lower extremities . Surgery. 1972;71:4-9. 46. Shepherd JT. Circulation to skeletal muscle . In: Shep herd JT, Abboud FM, Geiger SR, eds. Handbook of Physiology . Bethesda, Md: American Physiological Society; 1983:319-370. 47. Clausen JP. Circulatory adjustments to dynamic exercise and effect of physical training in normal subjects and in patients with coronary artery disease . Prog Cardiovasc Dis. 1976;18:459-495.Crossref 48. Longhurst J, Capone RJ, Mason DT, Zelis R. Comparison of blood flow measured by plethysmograph and flowmeter during steady state forearm exercise . Circulation. 1974;49:535-540.Crossref 49. Hillestad LK. The peripheral blood flow in intermittent claudication, VI: plethysmographic studies: the blood flow re sponse to exercise with arrested and with free circulation . Acta Med Scand. 1963;174:671-685.Crossref 50. Dahllof A-G, Holm J, Schersten T, Sivertsson R. Periph eral arterial insufficiency: effect of physical training on walking tolerance, calf blood flow, and blood flow resistance . Scand J Rehabil Med. 1976;8:19-26. 51. Eckroth R, Dahllof A-G, Gundevall B, Holm J, Schersten T. Physical training of patients with intermittent claudication: indications, methods, and results . Surgery. 1978;84:640-643. 52. Sorlie D, Myhre K. Effects of physical training in inter mittent claudication . Scand J Clin Lab Invest. 1978;38:217-222.Crossref 53. Dahllof A-G, Bjorntorp P, Holm J, Schersten T. Metabolic activity of skeletal muscle in patients with peripheral arterial insufficiency: effect of physical training . Eur J Clin Invest. 1974;4:9-15.Crossref 54. Kannel WB, Shurtleff D. The natural history of arterio sclerosis obliterans . Cardiovasc Clin. 1971;3:38-52. 55. Applegate WB. Hypertension in elderly patients . Ann In tern Med. 1989;110:901-915.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

ß-Adrenergic Blocker Therapy Does Not Worsen Intermittent Claudication in Subjects With Peripheral Arterial Disease: A Meta-analysis of Randomized Controlled Trials

Radack, Kenneth; Deck, Colleen
Archives of Internal Medicine , Volume 151 (9) – Sep 1, 1991
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References (61)

Publisher
American Medical Association
Copyright
Copyright © 1991 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1991.00400090063012
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Abstract

Abstract β-Adrenergic blockers have been considered relatively contraindicated in peripheral arterial disease because of the perceived risk that these drugs could worsen intermittent claudication. Therefore, we conducted a meta-analysis of available randomized controlled trials from the English-language literature to determine whether or not β-blockers exacerbate intermittent claudication. The primary focus of this analysis was the effect of β-blockers on exercise dura tion, measured as walking capacity or endurance time. Outcomes were pooled where appropriate. Of 11 eligible reports, six included 11 individual controlled treatment comparisons that provided data for an analysis of pain-free exercise capacity; no effect size was statistically significant. The pooled effect size for pain-free walking distance was -0.24 (95% confidence interval, -0.62 to 0.14), indicat ing no significant impairment of walking capacity compared with placebo. Only one study reported that certain β-blockers were associated with worsening of intermittent claudication. These results strongly suggest that β-blockers do not adversely affect walking capacity or symptoms of intermittent claudication in patients with mild to moderate peripheral arterial disease. In the absence of other con traindications, β-blockers can probably be used safely in such patients. (Arch Intern Med. 1991;151:1769-1776) References 1. Criqui MH, Fronek A, Barrett-Connor E, et al. The preva lence of peripheral arterial disease in a defined population . Circulation. 1985;71:510-515.Crossref 2. Lassila R, Lepantalo M, Lindfors O. Peripheral arterial disease: natural outcome . Acta Med Scand. 1986;220:295-301.Crossref 3. Kannel WB, Skinner JJ Jr, Schwartz MG, et al. Intermittent claudication: incidence in the Framingham Study . Circulation. 1970;41:875-883.Crossref 4. Kannel WB, McGee DL. Update on some epidemiologic features of intermittent claudication: the Framingham Study . J Am Geriatr Soc. 1985;33:13-18. 5. Hughson WG, Mann Jl, Garrod A. Intermittent claudication: prevalence and risk factors . BMJ. 1978;1:1379-1381.Crossref 6. Ramsay LE. Intermittent claudication in hypertensive men . J R Coll Phys Lond. 1979;13:100-102. 7. Sivertsson R, Andersson O, Hansson L. Blood pressure reduction in vascular adaption . Acta Med Scand. 1979;205:477-482.Crossref 8. George CF. Beta-receptor blocking agents . Prescribers J. 1974;14:93-98. 9. Frishman WH. Beta-adrenergic receptor blockers: ad verse effects and drug interactions . Hypertension. 1988;11( (suppl II) ):21-29.Crossref 10. Thulesius O. Beta-adrenergic blockade and vasospasm . Acta Med Scand. 1979;625( (suppl) ):41-43. 11. Lepantalo M. Beta blockade and intermittent claudica tion . Acta Med Scand. 1985;700( (suppl) ):1-48. 12. Breckenridge A. Which beta-blocker? BMJ. 1983;286:1085-1088.Crossref 13. Rodger JC, Sheldon CD, Lerski RA, Livingstone WR. In termittent claudication complicating beta-blockade . BMJ. 1976;1:1125.Crossref 14. Fogoros RN. Exacerbation of intermittent claudication by propranolol . N Engl J Med. 1980;302:1089. 15. Rodgers LD, Thieman KC, Mosier CL. Peripheral is chemia secondary to beta-blocker therapy . J lowa Med Soc. 1983;73:13-14. 16. Vale JA, Jefferys DB. Peripheral gangrene complicating beta-blockade . Lancet. 1978;1:1216.Crossref 17. Frohlich ED, Tarazi RC, Dustan HP. Peripheral arterial in sufficiency: a complication of beta-adrenergic blocking ther apy . JAMA. 1969;208:2471-2472.Crossref 18. Lepantalo M, Aromaa A, Klaukka T, Lukkari E. Does beta blockade provoke intermittent claudication? Acta Med Scand. 1985;218:35-39.Crossref 19. Lepantalo M, von Knorring J, Lindfors O, Scheinin TM. The effect of withdrawal of beta-adrenergic blockade on inter mittent claudication . Angiology. 1983;34:401-411.Crossref 20. Reichert N, Shibolet S, Adar R, Gafni J. Controlled trial of propranolol in intermittent claudication . Clin Pharmacol Ther. 1975;17:612-615. 21. Clement DL. Studies on the effect of alpha- and of beta-adrenergic blocking agents on the circulation in human limbs . Verh K Acad Geneeskd Belg. 1980;42:164-214. 22. Smith RS, Warren DJ. Effect of beta-blocking drugs on peripheral blood flow in intermittent claudication . J Cardiovasc Pharmacol. 1982;4:2-4.Crossref 23. Bogaert MG, Clement DL. Lack of influence of propra nolol and metoprolol on walking distance in patients with chronic intermittent claudication . Eur Heart J. 1983;4:203-204. 24. Lepantalo M, von Knorring J. Walking capacity of patients with intermittent claudication during chronic antihypertensive treatment with metoprolol and methyldopa . Clin Physiol. 1984;4:275-282.Crossref 25. Lepantalo M. Chronic effects of metoprolol and methyl dopa on calf blood flow in intermittent claudication . Br J Clin Pharmacol. 1984;18:90-93.Crossref 26. Hiatt WR, Stoll S, Nies AS. Effect of β-adrenergic block ers on the peripheral circulation in patients with peripheral vascular disease . Circulation. 1985;72:1226-1231.Crossref 27. Lepantalo M. Chronic effects of labetalol, pindolol, and propranolol on calf blood flow in intermittent claudication . Clin Pharmacol Ther. 1985;37:7-12.Crossref 28. Bostrom PA, Janzon L, Ohlsson O, Westergren A. The effect of beta-blockade on leg blood flow in hypertensive pa tients with intermittent claudication . Angiology. 1986;37:149-153.Crossref 29. Svendsen TL, Jelnes R, Tonnesen KH. The effects of acebutolol and metoprolol on walking distances and distal blood pressure in hypertensive patients with intermit tent claudication . Acta Med Scand. 1986;219:161-165.Crossref 30. Roberts DH, Tsao Y, McLoughlin GA, Breckenridge A. Placebo-controlled comparison of captopril, atenolol, labe talol, and pindolol in hypertension complicated by intermittent claudication . Lancet . 1987;1:650-653.Crossref 31. Sacks HS, Berrier J, Reitman D, et al. Meta-analysis of randomized controlled trials . N Engl J Med. 1987;316:450-455.Crossref 32. Chalmers TC, Smith H, Blackburn B, et al. A method for assessing the quality of a randomized controlled trial . Con trolled Clin Trials. 1981;2:31-49.Crossref 33. DerSimonian R, Charette LJ, McPeek B, Mosteller F. Re porting on methods in clinical trials . N Engl J Med. 1982;306:1332-1337.Crossref 34. Hedges LV, Olkin I. Statistical Methods for Meta-analysis. Orlando, Fla: Academic Press; 1985. 35. Lepantalo M, Totterman KJ. Effect of long-term betaadrenergic-blockade on calf blood flow in hypertensive pa tients . Clin Physiol. 1983;3:35-42.Crossref 36. Ingram DM, House AK, Thompson GH, Stacey MC, Castleden WM, Lovegrove FT. Beta-adrenergic blockade and peripheral vascular disease . Med J Aust. 1982;1:509-511. 37. McSorley PD, Warren DJ. Effects of propranolol and me toprolol on the peripheral circulation . BMJ. 1978;2:1598-1600.Crossref 38. Agerskov K. Effect of propranolol on the tone of collat eral arteries in patients with occlusion of the superficial femo ral artery . Clin Physiol. 1983;3:43-48.Crossref 39. Lepantalo M, Lindstrom BL, Totterman KJ. Adrenoceptor blocking drugs and cold feet in intermittent claudication . Vasa. 1986;15:135-137. 40. Vandenburg MJ. The acute and chronic effect on oxprenolol and propranolol on peripheral blood flow in hypertensive patients . Br J Clin Pharmacol. 1982;14:733-737.Crossref 41. Eliasson K, Lins LE, Sundqvist K. Peripheral vasospasm during beta-receptor blockade: a comparison between meto prolol and pindolol . Acta Med Scand. 1982;665:109-112. 42. Eliasson K, Lins LE, Sundqvist K. Vasospastic phenomena in patients treated with beta-adrenoceptor blocking agents . Acta Med Scand. 1978;628( (suppl) ):39-46. 43. Svendsen TL, Jelnes R, Tonnesen KH. Is adrenergic betareceptor blockade contraindicated in patients with intermittent claudication? Acta Med Scand. 1985;693( (suppl) ):129-132. 44. Cohen J. Statistical Power Analysis for the Behavioral Sciences . Hillsdale, NJ: Lawrence Erlbaum Assoc; 1988. 45. Yao JST, Needham TN, Gourmoos C, Irvine WT. A com parative study of strain-gauge plethysmography and Doppler ultrasound in the assessment of occlusive arterial disease of the lower extremities . Surgery. 1972;71:4-9. 46. Shepherd JT. Circulation to skeletal muscle . In: Shep herd JT, Abboud FM, Geiger SR, eds. Handbook of Physiology . Bethesda, Md: American Physiological Society; 1983:319-370. 47. Clausen JP. Circulatory adjustments to dynamic exercise and effect of physical training in normal subjects and in patients with coronary artery disease . Prog Cardiovasc Dis. 1976;18:459-495.Crossref 48. Longhurst J, Capone RJ, Mason DT, Zelis R. Comparison of blood flow measured by plethysmograph and flowmeter during steady state forearm exercise . Circulation. 1974;49:535-540.Crossref 49. Hillestad LK. The peripheral blood flow in intermittent claudication, VI: plethysmographic studies: the blood flow re sponse to exercise with arrested and with free circulation . Acta Med Scand. 1963;174:671-685.Crossref 50. Dahllof A-G, Holm J, Schersten T, Sivertsson R. Periph eral arterial insufficiency: effect of physical training on walking tolerance, calf blood flow, and blood flow resistance . Scand J Rehabil Med. 1976;8:19-26. 51. Eckroth R, Dahllof A-G, Gundevall B, Holm J, Schersten T. Physical training of patients with intermittent claudication: indications, methods, and results . Surgery. 1978;84:640-643. 52. Sorlie D, Myhre K. Effects of physical training in inter mittent claudication . Scand J Clin Lab Invest. 1978;38:217-222.Crossref 53. Dahllof A-G, Bjorntorp P, Holm J, Schersten T. Metabolic activity of skeletal muscle in patients with peripheral arterial insufficiency: effect of physical training . Eur J Clin Invest. 1974;4:9-15.Crossref 54. Kannel WB, Shurtleff D. The natural history of arterio sclerosis obliterans . Cardiovasc Clin. 1971;3:38-52. 55. Applegate WB. Hypertension in elderly patients . Ann In tern Med. 1989;110:901-915.Crossref

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Archives of Internal Medicine – American Medical Association

Published: Sep 1, 1991

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