Skip to main content
PMC home page
Clinical Cardiology logoLink to Clinical Cardiology
. 2009 Feb 3;22(9):559–573. doi: 10.1002/clc.4960220905

Antiplatelet therapy in the prevention of ischemic vascular events: Literature review and evidence‐based guidelines for drug selection

Randall M Zusman 1,✉, James H Chesebro 2, Anthony Comerota 3, Joseph R Hartmann 4, Edward K Massin 5, Eric Raps 6, Philip A Wolf 7
PMCID: PMC6655822  PMID: 10486695

Abstract

Background: New antiplatelet drugs are being developed and many clinical trials evaluating the benefits of antiplatelet drugs for the secondary prevention of ischemic events in patients with atherosclerotic vascular disease have been performed.

Hypothesis: An updated systematic review and evidence‐based guidelines for the appropriate selection of antiplatelet drugs may be beneficial to physicians and healthcare organizations attempting to create or update current clinical practice guidelines or clinical pathways aimed at caring for these patients.

Methods: (1) A systematic review of the recent literature on the relative efficacy and safety of aspirin, ticlopidine, and clopidogrel was undertaken; (2) an evidence‐based, expert panel approach using a modified Delphi technique to create explicit guidelines for prescribing antiplatelet therapy was instituted; and (3) the recommendations of an expert panel were summarized.

Results: Consensus guidelines were developed for the utilization of aspirin, ticlopidine, or clopidogrel for the prevention of ischemic events in patients with manifestations of atherosclerotic vascular disease (prior myocardial infarction, prior ischemic stroke, or established peripheral arterial disease) who are at increased risk for recurrent ischemic events. Based on efficacy and safety, clopidogrel was recommended as the drug of choice for patients with established peripheral arterial disease; aspirin or clopidogrel should be considered in patients with prior myocardial infarction (with clopidogrel favored for patients who have had a recurrent event while on aspirin or in whom aspirin is contraindicated); aspirin or clopidogrel should be considered as first‐line treatment in patients with prior ischemic (nonhemorrhagic) stroke‐however, clopidogrel is the favored drug in patients in whom other antiplatelet drugs are either contraindicated or who have had recurrent events while on therapy.

Conclusions: Myocardial infarction, ischemic stroke, and peripheral arterial disease are all clinical manifestations of the same underlying disease process (atherosclerosis), with thrombus formation on the disrupted atherosclerotic plaque (atherothrombosis) being a common precipitating factor of ischemic events in patients suffering from these disorders. An evidence‐based approach was used to develop a practice guideline, based on available published evidence, for the appropriate utilization of antiplatelet agents (aspirin, ticlopidine, or clopidogrel). These guidelines may be of use to multidisciplinary teams wishing to create or update clinical guidelines or clinical pathways which address the care of patients with atherosclerotic vascular disease. New antiplatelet agents such as clopidogrel may be more effective and associated with lower risk of selected adverse effects (such as gastrointestinal distress, gastrointestinal hemorrhage, and neutropenia) than those previously used to prevent thrombus formation in the setting of atherosclerotic arterial disease. Combination antiplatelet therapy is being evaluated as an option for those patients who experience recurrent events on a single antiplatelet agent.

Keywords: antiplatelet, atherosclerosis, evidence‐based, peripheral arterial disease, myocardial infarction, ischemic stroke

Full Text

The Full Text of this article is available as a PDF (1.4 MB).

References

  • 1. Kannel WB: Risk factors for atherosclerotic cardiovascular outcomes in different arterial territories. J Cardiovasc Risk 1994; 1: 333–339 [PubMed] [Google Scholar]
  • 2. Aronow WS, Ahn C: Prevalence of coexistence of coronary artery disease, peripheral arterial disease, and atherothrombotic brain infarction in men and women > or = 62 years of age. Am J Cardiol 1994; 74: 64–65 [DOI] [PubMed] [Google Scholar]
  • 3. Graves E, Gillum B: Detailed diagnoses and procedures, National Hospital Discharge Survey, 1995. Vital Health Stat 1997; 130: 1–146 [PubMed] [Google Scholar]
  • 4. Adams P, Marano M: Current estimates from the National Health Interview Survey, 1994. National Center for Health Statistics. Vital Health Stat 1995; 10: 83–84 [PubMed] [Google Scholar]
  • 5. Newman AB, Siscovick DS, Manolio TA, Polak J, Fried LP, Borhani NO, Wolfson SK: Ankle‐arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Cardiovascular Heart Study (CHS) Collaborative Research Group. Circulation 1993; 88: 837–845 [DOI] [PubMed] [Google Scholar]
  • 6. Fuster V, Badimon L, Badimon JJ, Chesebro JH: The pathogenesis of coronary artery disease and the acute coronary syndromes (1). N Engl J Med 1992; 326: 242–250 [DOI] [PubMed] [Google Scholar]
  • 7. Fuster V, Badimon L, Badimon JJ, Chesebro JH: The pathogenesis of coronary artery disease and the acute coronary syndromes (2). N Engl J Med 1992; 326: 310–318 [DOI] [PubMed] [Google Scholar]
  • 8. Davies MJ, Richardson PD, Woolf N, Katz DR, Mann J: Risk of thrombosis in human atherosc lerotic plaques: Role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J 1993; 69: 377–381 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Toschi V, Gallo R, Lettino M, Fallon JT, Gertz SD, Fernandez‐Ortiz A, Chesebro JH, Badimon L, Nemerson Y, Fuster V, Badimon JJ: Tissue factor modulates the thrombogenicity of human atherosclerotic plaques. Circulation 1997; 95: 594–599 [DOI] [PubMed] [Google Scholar]
  • 10. Schafer AI: Antiplatelet therapy. Am J Med 1996; 101: 199–209 [DOI] [PubMed] [Google Scholar]
  • 11. Di PG, Andreoli A, Pinelli G, Grazi P, Manini G, Tognetti F, Testa C: Cerebral ischemia and asymptomatic coronary artery disease: A prospective study of 83 patients. Stroke 1986; 17: 1098–1101 [DOI] [PubMed] [Google Scholar]
  • 12. Hertzer NR: Basic data concerning associated coronary disease in peripheral vascular patients. Ann Vasc Surg 1987; 1: 616–620 [DOI] [PubMed] [Google Scholar]
  • 13. Criqui MH, Langer RD, Fronek A, Feigelson HS, Klauber MR, McCann TJ, Browner D: Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med 1992; 326: 381–386 [DOI] [PubMed] [Google Scholar]
  • 14. Hirsh J, Dalen JE, Fuster V, Harker LB, Patrono C, Roth G: Aspirin and other platelet‐active drugs. The relationship among dose, effectiveness, and side effects. Chest 1995; 108:247S–257S [DOI] [PubMed] [Google Scholar]
  • 15. Field M, Lohr K: Clinical Practice Guidelines: Directions for a New Program. Washington, D.C.: National Academy Press, 1990. [PubMed] [Google Scholar]
  • 16. Weingarten S: Practice guidelines and prediction rules should be subject to careful clinical testing. J Am Med Assoc 1997; 277: 1977–1978 [PubMed] [Google Scholar]
  • 17. Cook DJ, Greengold N, Ellrodt A, Weingarten S: The relation between systematic reviews and clinical guidelines. Ann Intern Med 1997; 127: 210–216 [DOI] [PubMed] [Google Scholar]
  • 18. Ellrodt A, Cook DJ, Lee J, Cho M, Hunt D, Weingarten S: Evidence‐based disease management. J Am Med Assoc 1997; 278: 1687–1692 [PubMed] [Google Scholar]
  • 19. Grimshaw J, Russell I: Effect of clinical guidelines on medical practice: A systematic review of rigorous evaluations. Lancet 1993; 342: 1317–1322 [DOI] [PubMed] [Google Scholar]
  • 20. Anonymous : 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. Antiplatelet Trialists' Collaboration. Br Med J 1994; 308: 81–106 [PMC free article] [PubMed] [Google Scholar]
  • 21. Weitz JI, Califf RM, Ginsberg JS, Hirsh J, Théroux P: New antithrombotics. Chest 1995; 108:471S–485S [DOI] [PubMed] [Google Scholar]
  • 22. Verstraete M: New developments in antiplatelet and antithrombotic therapy. Eur Heart J 1995; 16 (suppl L): 16–23 [DOI] [PubMed] [Google Scholar]
  • 23. Clagett GP, Krupski WC: Antithrombotic therapy in peripheral arterial occlusive disease. Chest 1995; 108:431S–443S [DOI] [PubMed] [Google Scholar]
  • 24. Sherman DG, Dyken MLJ, Gent M, Harrison JG, Hart RG, Mohr JP: Antithrombotic therapy for cerebrovascular disorders. An update. Chest 1995; 108:444S–456S [DOI] [PubMed] [Google Scholar]
  • 25. Hennekens CH: Aspirin in the treatment and prevention of cardiovascular disease. Ann Rev Publ Health 1997; 18: 37–49 [DOI] [PubMed] [Google Scholar]
  • 26. Rodgers A, MacMahon S: Antiplatelet therapy and the prevention of thrombosis. Austral NZ J Med 1996; 26: 210–215 [DOI] [PubMed] [Google Scholar]
  • 27. Schror K: Antiplatelet drugs. A comparative review. Drugs 1995; 50: 7–28 [DOI] [PubMed] [Google Scholar]
  • 28. Bendixen BH, Adams HP: Ticlopidine or clopidogrel as alternatives to aspirin in prevention of ischemic stroke. Eur Neurol 1996; 36: 256–257 [PubMed] [Google Scholar]
  • 29. Brint SU: Acute stroke therapies. Surg Neurol 1996; 46: 446–449 [DOI] [PubMed] [Google Scholar]
  • 30. Albers GW: Antithrombotic agents in cerebral ischemia. Am J Cardiol 1995; 75:34B–38B [DOI] [PubMed] [Google Scholar]
  • 31. Barnett HJ, Eliasziw M, Meldrum HE: Drugs and surgery in the prevention of ischemic stroke. N Engl J Med 1995; 332: 238–248 [DOI] [PubMed] [Google Scholar]
  • 32. Bronner LL, Kanter DS, Manson JE: Primary prevention of stroke. N Engl J Med 1995; 333: 1392–1400 [DOI] [PubMed] [Google Scholar]
  • 33. Kamat SG, Kleiman NS: Platelets and platelet inhibitors in acute myocardial infarction. Cardiol Clin 1995; 13: 435–447 [PubMed] [Google Scholar]
  • 34. Cook DJ, Guyatt GH, Laupacis A, Sackett DL, Goldberg RJ: Clinical recommendations using levels of evidence for antithrombotic agents. Chest 1995; 108:227S–230S [DOI] [PubMed] [Google Scholar]
  • 35. Anonymous : A randomised, blinded trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 1996; 348: 1329–1339 [DOI] [PubMed] [Google Scholar]
  • 36. Linstone H, Turoff M: The Delphi Method: Techniques and Applications. Reading, Massachusetts: Addison‐Wesley Publishing Company, 1975. [Google Scholar]
  • 37. Kahn K, Roth C, Fink A, Keesy J, Brook R, Park R, Chassin M, Solomon D: Indications for selected medical and surgical procedures: A literature review and ratings of appropriateness Colonoscopy. Santa Monica, Calif.: Rand Corp., 1986. [Google Scholar]
  • 38. Winslow CM, Solomon DH, Chassin MR, Kosecoff J, Merrick NJ, Brook RH: The appropriateness of carotid endarterectomy. N Engl J Med 1988; 318: 721–727 [DOI] [PubMed] [Google Scholar]
  • 39. Patrono C: Aspirin as an antiplatelet drug. N Engl J Med 1994; 330: 1287–1294 [DOI] [PubMed] [Google Scholar]
  • 40. Roth GJ, Calverley DC: Aspirin, platelets, and thrombosis: Theory and practice. Blood 1994; 83: 885–898 [PubMed] [Google Scholar]
  • 41. Anonymous : Secondary prevention of vascular disease by prolonged antiplatelet treatment. Antiplatelet Trialists' Collaboration. Br Med J Clin Res Ed 1988; 296: 320–331 [PMC free article] [PubMed] [Google Scholar]
  • 42. Stalnikowicz‐Darvasi R: Gastrointestinal bleeding during low‐dose aspirin administration for prevention of arterial occlusive events. A critical analysis. J Clin Gastroenterol 1995; 21: 13–16 [PubMed] [Google Scholar]
  • 43. Roderick PJ, Wilkes HC, Meade TW: The gastrointestinal toxicity of aspirin: An overview of randomised controlled trials. Br J Clin Pharmacol 1993; 35: 219–226 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44. Helgason CM, Bolin KM, Hoff JA, Winkler SR, Mangat A, Tortorice KL, Brace LD: Development of aspirin resistance in persons with previous ischemic stroke. Stroke 1994; 25: 2331–2336 [DOI] [PubMed] [Google Scholar]
  • 45. Humbert M, Nurden P, Bihour C, Pasquet JM, Winckler J, Heilmann E, Savi Herbert JM, Kunicki TJ, Nurden AT: Ultrastructural studies of platelet aggregates from human subjects receiving clopidogrel and from a patient with an inherited defect of an ADP‐dependent pathway of platelet activation. Arterioscl Thromb Vasc Biol 1996; 16: 1532–1543 [DOI] [PubMed] [Google Scholar]
  • 46. Mills DC, Puri R, Hu CJ, Minniti C, Grana G, Freedman MD, Colman RF, Colman RW: Clopidogrel inhibits the binding of ADP analogues to the receptor mediating inhibition of platelet adenylate cyclase. Arterioscl Thromb 1992; 12: 430–436 [DOI] [PubMed] [Google Scholar]
  • 47. Nurden AT: New thoughts on strategies for modulating platelet function through the inhibition of surface receptors. Haemostasis 1996; 26 (suppl 4): 78–88 [DOI] [PubMed] [Google Scholar]
  • 48. Saltiel E, Ward A: Ticlopidine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in platelet‐dependent disease states. Drugs 1987; 34: 222–262 [DOI] [PubMed] [Google Scholar]
  • 49. Lutomski DM, Bottorff M, Sangha K: Pharmacokinetic optimisation of the treatment of embolic disorders. Clin Pharmacokinet 1995; 28: 67–92 [DOI] [PubMed] [Google Scholar]
  • 50. Herbert JM, Frehel D, Vallee E, Kieffer G, Gouy D, Berger Y, Necciari J, Defreyn G, Maffrand JP: Clopidogrel, a novel antiplatelet and antithrombotic agent. Cardiovasc Drug Rev 1993; 11: 180–198 [Google Scholar]
  • 51. Anonymous : Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS‐2. ISIS‐2 (Second International Study of Infarct Survival) Collaborative Group. Lancet 1988; 2: 349–360 [PubMed] [Google Scholar]
  • 52. Anonymous : The International Stroke Trial (IST): A randomised trial of aspirin, subcutaneous heparin, both, or neither among 19,435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet 1997; 349: 1569–1581 [PubMed] [Google Scholar]
  • 53. Anonymous : CAST: Randomised placebo‐controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet 1997; 349: 1641–1649 [PubMed] [Google Scholar]
  • 54. Gent M, Blakely JA, Easton JD, Ellis DJ, Hachinski VC, Harbison JW, Panak E, Roberts RS, Sicurella J, Turpie AG: The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Lancet 1989; 1: 1215–1220 [DOI] [PubMed] [Google Scholar]
  • 55. Hass WK, Easton JD, Adams HP Jr, Pryse‐Phillips W, Molony BA, Anderson S, Kamm B: A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high‐risk patients. Ticlopidine Aspirin Stroke Study Group. N Engl J Med 1989; 321: 501–507 [DOI] [PubMed] [Google Scholar]
  • 56. Janzon L, Bergqvist D, Boberg J, Boberg M, Eriksson I, Lindgarde F, Persson G: Prevention of myocardial infarction and stroke in patients with intermittent claudication: Effects of ticlopidine. Results from STIMS, the Swedish Ticlopidine Multicentre Study. J Intern Med 1990; 227: 301–308 [DOI] [PubMed] [Google Scholar]
  • 57. Gent M: Benefit of clopidogrel in patients with coronary disease. Circulation 1997; 96 (suppl): 2608 [Google Scholar]
  • 58. Kuller LH, Shemanski L, Psaty BM, Borhani NO, Gardin J, Haan MN O'Leary DH, Savage PJ, Tell GS, Tracy R: Subclinical disease as an independent risk factor for cardiovascular disease. Circulation 1995; 92: 720–726 [DOI] [PubMed] [Google Scholar]
  • 59. Cote R, Battista RN, Abrahamowicz M, Langlois Y, Bourque F, Mackey A: Lack of effect of aspirin in asymptomatic patients with carotid bruits and substantial carotid narrowing. The Asymptomatic Cervical Bruit Study Group. Ann Intern Med 1995; 123: 649–655 [DOI] [PubMed] [Google Scholar]
  • 60. Anonymous : Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. J Am Med Assoc 1995; 273: 1421–1428 [PubMed] [Google Scholar]
  • 61. Brott T, Toole JF: Medical compared with surgical treatment of asymptomatic carotid artery stenosis. Ann Intern Med 1995; 123: 720–722 [DOI] [PubMed] [Google Scholar]
  • 62. Young B, Moore WS, Robertson JT, Toole JF, Ernst CB, Cohen SN, Broderick JP, Dempsey RJ, Hosking JD: An analysis of perioperative surgical mortality and morbidity in the asymptomatic carotid atherosclerosis study. ACAS Investigators. Asymptomatic Carotid Artheriosclerosis Study. Stroke 1996; 27: 2216–2224 [DOI] [PubMed] [Google Scholar]
  • 63. Peto R, Gray R, Collins R, Wheatley K, Hennekens C, Jamrozik K, Warlow C, Hafner B, Thompson E, Norton S, Gilliand J, Doll R: Randomised trial of prophylactic daily aspirin in British male doctors. Br Med J Clin Res Ed 1988; 296: 313–316 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64. Col NF, Yarzbski J, Gore JM, Alpert JS, Goldberg RJ: Does aspirin consumption affect the presentation or severity of acute myocardial infarction? Arch Intern Med 1995; 155: 1386–1389 [PubMed] [Google Scholar]
  • 65. Manson JE, Stampfer MJ, Colditz GA, Willett WC, Rosner B, Speizer FE, Hennekens CH: A prospective study of aspirin use and primary prevention of cardiovascular disease in women. J Am Med Assoc 1991; 266: 521–527 [PubMed] [Google Scholar]
  • 66. Anonymous : Final report on the aspirin component of the ongoing Physicians' Health Study. Steering Committee of the Physicians' Health Study Research Group. N Engl J Med 1989; 321: 129–135 [DOI] [PubMed] [Google Scholar]
  • 67. Ishikawa K, Kanamasa K, Hama J, Ogawa I, Takenaka T, Naito T, Yamamoto T, Nakai S, Oyaizu M, Kimura A, Yamamoto K, Katori R: Aspirin plus either dipyridamole or ticlopidine is effective in preventing recurrent myocardial infarction. Secondary Prevention Group. Jpn Circ J 1997; 61: 38–45 [DOI] [PubMed] [Google Scholar]
  • 68. Balsano F, Rizzon P, Violi F, Scrutinio D, Cimminiello C, Aguglia F, Pasotti C, Rudelli G: Antiplatelet treatment with ticlopidine in unstable angina. A controlled multicenter clinical trial. The Studio della Ticlopidina nell'Angina Instabile Group. Circulation 1990; 82: 17–26 [DOI] [PubMed] [Google Scholar]
  • 69. Neumann FJ, Gawaz M, Dickfeld T, Wehinger A, Walter H, Blasini R, Schomig A: Antiplatelet effect of ticlopidine after coronary stenting. J Am Coll Cardiol 1997; 29: 1515–1519 [DOI] [PubMed] [Google Scholar]
  • 70. Schomig A, Neumann FJ, Kastrati A, Schuhlen H, Blasini R, Hadamitzky M, Walter H, Zitzmann‐Roth EM, Richardt G, Alt E, Schmitt TA, Ulm K: A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary‐artery stents. N Engl J Med 1996; 334: 1084–1089 [DOI] [PubMed] [Google Scholar]
  • 71. Anonymous : States of insulin resistance: The interaction between hypertension, glucose intolerance, and coronary heart disease. Proceedings of a symposium. Montreal, Canada, June 24, 1990. Am Heart J 1991; 121: 1267–1318 [PubMed] [Google Scholar]
  • 72. Paffenbarger RSJ, Hyde RT, Wing AL, Lee IM, Jung DL, Kampert JB: The association 250 of changes in physical‐activity level and other lifestyle characteristics with mortality among men. N Engl J Med 1993; 328: 538–545 [DOI] [PubMed] [Google Scholar]
  • 73. Haskell WL, Alderman EL, Fair JM, Maron DJ, Mackey SF, Superko HR, Williams PT, Johnstone IM, Champagne MA, Krauss RM: Effects of intensive multiple risk factor reduction on coronary atherosclerosis and clinical cardiac events in men and women with coronary artery disease. The Stanford Coronary Risk Intervention Project (SCRIP). Circulation 1994; 89: 975–990 [DOI] [PubMed] [Google Scholar]
  • 74. Diener HC, Cunha L, Forbes C, Sivenius J, Smets P, Lowenthal A: European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996; 143: 1–13 [DOI] [PubMed] [Google Scholar]
  • 75. Anonymous : Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Multicentre Acute Stroke Trial—Italy (MAST‐I) Group. Lancet 1995; 346: 1509–1514 [PubMed] [Google Scholar]
  • 76. Anonymous : Swedish Aspirin Low‐Dose Trial (SALT) of 75 mg aspirin as secondary prophylaxis after cerebrovascular ischaemic events. The SALT Collaborative Group. Lancet 1991; 338: 1345–1349 [PubMed] [Google Scholar]
  • 77. Farrell B, Godwin J, Richards S, Warlow C: The United Kingdom transient ischaemic attack (UK‐TIA) aspirin trial: Final results. J Neurol Neurosurg Psychiatry 1991; 54: 1044–1054 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 78. Juul‐Moller S, Edvardsson N, Jahnmatz B, Rosen A, Sorensen S, Omblus R: Double‐blind trial of aspirin in primary prevention of myocardial infarction in patients with stable chronic angina pectoris. The Swedish Angina Pectoris Aspirin Trial (SAPAT) Group. Lancet 1992; 340: 1421–1425 [DOI] [PubMed] [Google Scholar]
  • 79. Klimt CR, Knatterud GL, Stamler J, Meier P: Persantine‐Aspirin Reinfarction Study. Part II. Secondary coronary prevention with persantine and aspirin. J Am Coll Cardiol 1986; 7: 251–269 [DOI] [PubMed] [Google Scholar]
  • 80. Anonymous : The aspirin myocardial infarction study: Final results. The Aspirin Myocardial Infarction Study research group. Circulation 1980; 62: V79–V84 [PubMed] [Google Scholar]
  • 81. Anonymous : Aspirin in coronary heart disease. The Coronary Drug Project Research Group. Circulation 1980; 62: V59–V62 [PubMed] [Google Scholar]
  • 82. Breddin K, Loew D, Lechner K, Oberla K, Walter E: The German‐Austrian aspirin trial: A comparison of acetylsalicylic acid, placebo and phenprocoumon in secondary prevention of myocardial infarction. On behalf of the German‐Austrian Study Group. Circulation 1980; 62:V63‐72 [PubMed] [Google Scholar]
  • 83. Ciocon JO, Galindo‐Ciocon D, Galindo DJ: A comparison between aspirin and pentoxifylline in relieving claudication due to peripheral vascular disease in the elderly. Angiology 1997; 48: 237–240 [DOI] [PubMed] [Google Scholar]
  • 84. Minar E, Ahmadi A, Koppensteiner R, Maca T, Stumpflen A, Ugurluoglu A, Ehringer H: Comparison of effects of high‐dose and low‐dose aspirin on restenosis after femoropopliteal percutaneous transluminal angioplasty. Circulation 1995; 91: 2167–2173 [DOI] [PubMed] [Google Scholar]
  • 85. Balsano F, Coccheri S, Libretti A, Nenci GG, Catalano M, Fortunato G, Grasselli S, Violi F, Hellemans H, Vanhove P: Ticlopidine in the treatment of intermittent claudication: A 21 ‐ month double‐blind trial. J Lab Clin Med 1989; 114: 84–91 [PubMed] [Google Scholar]
  • 86. 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 1988; 39: 802–811 [DOI] [PubMed] [Google Scholar]

Articles from Clinical Cardiology are provided here courtesy of Wiley

RESOURCES