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. 1994 Jan 15;308(6922):159–168.

Collaborative overview of randomised trials of antiplatelet therapy--II: Maintenance of vascular graft or arterial patency by antiplatelet therapy. Antiplatelet Trialists' Collaboration.

PMCID: PMC2542519  PMID: 8312766

Abstract

OBJECTIVE--To determine the efficacy of antiplatelet therapy in maintaining vascular patency in various categories of patients. DESIGN--Overviews of 46 randomised trials of antiplatelet therapy versus control and 14 randomised trials comparing one antiplatelet regimen with another. SETTING--Randomised trials that could have been available by March 1990 and in which vascular graft or arterial patency was to be studied systematically. SUBJECTS--About 8000 patients at varying degrees of risk of vascular occlusion (by virtue of disease or of having some vascular procedure) were in trials of antiplatelet therapy versus control and 4000 such patients were in trials directly comparing different antiplatelet regimens. RESULTS--Overall, antiplatelet therapy produced a highly significant (2P < 0.0001) reduction in vascular occlusion, with similar proportional reductions in several different types of patients. Hence the absolute reductions tended to be largest among patients at highest risk of occlusion, with smaller but still significant absolute reductions among lower risk patients. The proportions of patients with confirmed occlusion among those allocated antiplatelet therapy versus appropriately adjusted control proportions (and mean scheduled treatment durations and net absolute benefits) were: (a) among about 4000 patients with coronary artery grafts, 21% antiplatelet therapy v 30% control (seven month benefit about 90 patients protected per 1000 allocated antiplatelet therapy (2P < 0.00001)); (b) among about 800 patients after coronary angioplasty, 4% antiplatelet therapy v 8% control (six month benefit about 40/1000 (2P = 0.02)); (c) among about 3000 patients with peripheral artery procedures or disease, 16% antiplatelet therapy v 25% control (19 month benefit about 90/1000 (2P < 0.00001)); (d) among about 400 renal patients with a shunt or fistula placed for haemodialysis access, 17% antiplatelet therapy v 39% control (two month benefit about 200/1000 (2P < 0.00001)). Indirect comparisons between the effects of starting treatment before these vascular procedures and starting soon after them indicated similar sized benefits. As well as preventing subclinical occlusion, antiplatelet therapy produced a significant (2P = 0.002) reduction of about one quarter in the odds of suffering a "vascular event" (non-fatal myocardial infarction, non-fatal stroke, or vascular death). Various antiplatelet regimens (chiefly aspirin alone or aspirin plus dipyridamole) were studied but there was no significant evidence of differences between their effects on arterial occlusion or vascular events. Data on bleeding were incomplete but no large excess with antiplatelet therapy was apparent. CONCLUSION--Antiplatelet therapy (chiefly aspirin alone or aspirin plus dipyridamole) greatly reduces the risk of vascular occlusion in a wide range of patients at high risk of this complication. Further studies are required to determine exactly when treatment should start (to limit any perioperative bleeding while still preventing most early occlusion) and for how long it should be continued.

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Selected References

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  1. Andrassy K., Malluche H., Bornefeld H., Comberg M., Ritz E., Jesdinsky H., Möhring K. Prevention of p.o. clotting of av. cimino fistulae with acetylsalicyl acid. Results of a prospective double blind study. Klin Wochenschr. 1974 Apr 1;52(7):348–349. doi: 10.1007/BF01468835. [DOI] [PubMed] [Google Scholar]
  2. Baur H. R., VanTassel R. A., Pierach C. A., Gobel F. L. Effects of sulfinpyrazone on early graft closure after myocardial revascularization. Am J Cardiol. 1982 Feb 1;49(2):420–424. doi: 10.1016/0002-9149(82)90519-7. [DOI] [PubMed] [Google Scholar]
  3. Boehme K., Loew D., Artik N. Planung, Durchführung und biometrische Auswertung einer Langzeitstudie mit Acetylsalicylsäure. Med Welt. 1977 Jul 1;28(26):1163–1166. [PubMed] [Google Scholar]
  4. Bollinger A., Brunner U. Antiplatelet drugs improve the patency rates after femoro-popliteal endarterectomy. Vasa. 1985;14(3):272–279. [PubMed] [Google Scholar]
  5. Bonchek L. I., Boerboom L. E., Olinger G. N., Pepper J. R., Munns J., Hutchinson L., Kissebah A. H. Prevention of lipid accumulation in experimental vein bypass grafts by antiplatelet therapy. Circulation. 1982 Aug;66(2):338–341. doi: 10.1161/01.cir.66.2.338. [DOI] [PubMed] [Google Scholar]
  6. Brooks N., Wright J., Sturridge M., Pepper J., Magee P., Walesby R., Layton C., Honey M., Balcon R. Randomised placebo controlled trial of aspirin and dipyridamole in the prevention of coronary vein graft occlusion. Br Heart J. 1985 Feb;53(2):201–207. doi: 10.1136/hrt.53.2.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brown B. G., Cukingnan R. A., DeRouen T., Goede L. V., Wong M., Fee H. J., Roth J. A., Carey J. S. Improved graft patency in patients treated with platelet-inhibiting therapy after coronary bypass surgery. Circulation. 1985 Jul;72(1):138–146. doi: 10.1161/01.cir.72.1.138. [DOI] [PubMed] [Google Scholar]
  8. Campeau L., Enjalbert M., Lespérance J., Bourassa M. G., Kwiterovich P., Jr, Wacholder S., Sniderman A. The relation of risk factors to the development of atherosclerosis in saphenous-vein bypass grafts and the progression of disease in the native circulation. A study 10 years after aortocoronary bypass surgery. N Engl J Med. 1984 Nov 22;311(21):1329–1332. doi: 10.1056/NEJM198411223112101. [DOI] [PubMed] [Google Scholar]
  9. Castelli P., Basellini A., Agus G. B., Ippolito E., Pogliani E. M., Colombi M., Gianese F., Scatigna M. Thrombosis prevention with ticlopidine after femoropopliteal thromboendarterectomy. Int Surg. 1986 Oct-Dec;71(4):252–255. [PubMed] [Google Scholar]
  10. Chesebro J. H., Clements I. P., Fuster V., Elveback L. R., Smith H. C., Bardsley W. T., Frye R. L., Holmes D. R., Jr, Vlietstra R. E., Pluth J. R. A platelet-inhibitor-drug trial in coronary-artery bypass operations: benefit of perioperative dipyridamole and aspirin therapy on early postoperative vein-graft patency. N Engl J Med. 1982 Jul 8;307(2):73–78. doi: 10.1056/NEJM198207083070201. [DOI] [PubMed] [Google Scholar]
  11. Chesebro J. H., Fuster V., Elveback L. R., Clements I. P., Smith H. C., Holmes D. R., Jr, Bardsley W. T., Pluth J. R., Wallace R. B., Puga F. J. Effect of dipyridamole and aspirin on late vein-graft patency after coronary bypass operations. N Engl J Med. 1984 Jan 26;310(4):209–214. doi: 10.1056/NEJM198401263100401. [DOI] [PubMed] [Google Scholar]
  12. Chesebro J. H., Fuster V. Pathogenesis and prevention of aortocoronary bypass graft occlusion. Int J Clin Pharmacol Res. 1986;6(4):261–267. [PubMed] [Google Scholar]
  13. Chevigné M., David J. L., Rigo P., Limet R. Effect of ticlopidine on saphenous vein bypass patency rates: a double-blind study. Ann Thorac Surg. 1984 May;37(5):371–378. doi: 10.1016/s0003-4975(10)60757-6. [DOI] [PubMed] [Google Scholar]
  14. Collins R., Gray R., Godwin J., Peto R. Avoidance of large biases and large random errors in the assessment of moderate treatment effects: the need for systematic overviews. Stat Med. 1987 Apr-May;6(3):245–254. doi: 10.1002/sim.4780060308. [DOI] [PubMed] [Google Scholar]
  15. Comberg H. U., Janssen E. J., Diehm C., Zimmermann R., Harenberg J., Walter E., Oster P., Allenberg J., Horsch A. K., Mörl H. Sulfinpyrazon (Anturan) versus Placebo nach operativer Rekonstruktion der Oberschenkeletage bei arterieller Verschlusskrankheit. Vasa. 1983;12(2):172–178. [PubMed] [Google Scholar]
  16. Detre K., Holubkov R., Kelsey S., Cowley M., Kent K., Williams D., Myler R., Faxon D., Holmes D., Jr, Bourassa M. Percutaneous transluminal coronary angioplasty in 1985-1986 and 1977-1981. The National Heart, Lung, and Blood Institute Registry. N Engl J Med. 1988 Feb 4;318(5):265–270. doi: 10.1056/NEJM198802043180501. [DOI] [PubMed] [Google Scholar]
  17. Ehresmann U., Alemany J., Loew D. Prophylaxe von Rezidivverschlüssen nach Revaskularisations-eingriffen mit Acetylsalicylsäure. Ergebnisse einer doppeltblinden Langzeitstudie. Med Welt. 1977 Jul 1;28(26):1157–1162. [PubMed] [Google Scholar]
  18. Ekeström S. A., Gunnes S., Brodin U. B. Effect of dipyridamole (Persantin) on blood flow and patency of aortocoronary vein bypass grafts. Scand J Thorac Cardiovasc Surg. 1990;24(3):191–196. doi: 10.3109/14017439009098068. [DOI] [PubMed] [Google Scholar]
  19. Finci L., Höfling B., Ludwig B., Bulitta M., Steffenino G., Etti H., Meier B. Sulotroban during and after coronary angioplasty. A double-blind, placebo controlled study. Z Kardiol. 1989;78 (Suppl 3):50–54. [PubMed] [Google Scholar]
  20. Fiskerstrand C. E., Thompson I. W., Burnet M. E., Williams P., Anderton J. L. Double-blind randomized trial of the effect of ticlopidine in arteriovenous fistulas for hemodialysis. Artif Organs. 1985 Feb;9(1):61–63. doi: 10.1111/j.1525-1594.1985.tb04349.x. [DOI] [PubMed] [Google Scholar]
  21. Fuster V., Chesebro J. H. Role of platelets and platelet inhibitors in aortocoronary artery vein-graft disease. Circulation. 1986 Feb;73(2):227–232. doi: 10.1161/01.cir.73.2.227. [DOI] [PubMed] [Google Scholar]
  22. Gavaghan T. P., Hickie J. B., Krilis S. A., Baron D. W., Gebski V., Low J., Chesterman C. N. Increased plasma beta-thromboglobulin in patients with coronary artery vein graft occlusion: response to low dose aspirin. J Am Coll Cardiol. 1990 May;15(6):1250–1258. doi: 10.1016/s0735-1097(10)80009-9. [DOI] [PubMed] [Google Scholar]
  23. Gillum R. F. Coronary artery bypass surgery and coronary angiography in the United States, 1979-1983. Am Heart J. 1987 May;113(5):1255–1260. doi: 10.1016/0002-8703(87)90952-5. [DOI] [PubMed] [Google Scholar]
  24. Goldman M., Hall C., Dykes J., Hawker R. J., McCollum C. N. Does 111indium-platelet deposition predict patency in prosthetic arterial grafts? Br J Surg. 1983 Oct;70(10):635–638. doi: 10.1002/bjs.1800701019. [DOI] [PubMed] [Google Scholar]
  25. Goldman S., Copeland J., Moritz T., Henderson W., Zadina K., Ovitt T., Doherty J., Read R., Chesler E., Sako Y. Improvement in early saphenous vein graft patency after coronary artery bypass surgery with antiplatelet therapy: results of a Veterans Administration Cooperative Study. Circulation. 1988 Jun;77(6):1324–1332. doi: 10.1161/01.cir.77.6.1324. [DOI] [PubMed] [Google Scholar]
  26. Goldman S., Copeland J., Moritz T., Henderson W., Zadina K., Ovitt T., Kern K. B., Sethi G., Sharma G. V., Khuri S. Starting aspirin therapy after operation. Effects on early graft patency. Department of Veterans Affairs Cooperative Study Group. Circulation. 1991 Aug;84(2):520–526. doi: 10.1161/01.cir.84.2.520. [DOI] [PubMed] [Google Scholar]
  27. Green R. M., Roedersheimer L. R., DeWeese J. A. Effects of aspirin and dipyridamole on expanded polytetrafluoroethylene graft patency. Surgery. 1982 Dec;92(6):1016–1026. [PubMed] [Google Scholar]
  28. Guiteras P., Altimiras J., Arís A., Augé J. M., Bassons T., Bonal J., Caralps J. M., Castellarnau C., Crexells C., Masotti M. Prevention of aortocoronary vein-graft attrition with low-dose aspirin and triflusal, both associated with dipyridamole: a randomized, double-blind, placebo-controlled trial. Eur Heart J. 1989 Feb;10(2):159–167. doi: 10.1093/oxfordjournals.eurheartj.a059456. [DOI] [PubMed] [Google Scholar]
  29. Harajola P. T., Meurala H., Frick M. H. Prevention of early reocclusion by dipyridamole and ASA in arterial reconstructive surgery. J Cardiovasc Surg (Torino) 1981 Mar-Apr;22(2):141–144. [PubMed] [Google Scholar]
  30. Harter H. R., Burch J. W., Majerus P. W., Stanford N., Delmez J. A., Anderson C. B., Weerts C. A. Prevention of thrombosis in patients on hemodialysis by low-dose aspirin. N Engl J Med. 1979 Sep 13;301(11):577–579. doi: 10.1056/NEJM197909133011103. [DOI] [PubMed] [Google Scholar]
  31. Heiss H. W., Just H., Middleton D., Deichsel G. Reocclusion prophylaxis with dipyridamole combined with acetylsalicylic acid following PTA. Angiology. 1990 Apr;41(4):263–269. doi: 10.1177/000331979004100402. [DOI] [PubMed] [Google Scholar]
  32. Hess H., Müller-Fassbender H., Ingrisch H., Mietaschk A. Verhütung von Wiederverschlüssen nach Rekanalisation obliterierter Arterien mit der Kathetermethode. Dtsch Med Wochenschr. 1978 Dec 15;103(50):1994–1997. doi: 10.1055/s-0028-1129383. [DOI] [PubMed] [Google Scholar]
  33. Holden M. P. Dangers of aspirin before cardiac surgery. BMJ. 1992 Aug 8;305(6849):365–366. doi: 10.1136/bmj.305.6849.365-d. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Israel D. H., Adams P. C., Stein B., Chesebro J. H., Fuster V. Antithrombotic therapy in the coronary vein graft patient. Clin Cardiol. 1991 Apr;14(4):283–295. doi: 10.1002/clc.4960140403. [DOI] [PubMed] [Google Scholar]
  35. Kaegi A., Pineo G. F., Shimizu A., Trivedi H., Hirsh J., Gent M. Arteriovenous-shunt thrombosis. Prevention by sulfinpyrazone. N Engl J Med. 1974 Feb 7;290(6):304–306. doi: 10.1056/NEJM197402072900604. [DOI] [PubMed] [Google Scholar]
  36. Kaegi A., Pineo G. F., Shimizu A., Trivedi H., Hirsh J., Gent M. The role of sulfinpyrazone in the prevention of arterio-venous shunt thrombosis. Circulation. 1975 Sep;52(3):497–499. doi: 10.1161/01.cir.52.3.497. [DOI] [PubMed] [Google Scholar]
  37. Kohler T. R., Kaufman J. L., Kacoyanis G., Clowes A., Donaldson M. C., Kelly E., Skillman J., Couch N. P., Whittemore A. D., Mannick J. A. Effect of aspirin and dipyridamole on the patency of lower extremity bypass grafts. Surgery. 1984 Sep;96(3):462–466. [PubMed] [Google Scholar]
  38. Limet R., David J. L., Magotteaux P., Larock M. P., Rigo P. Prevention of aorta-coronary bypass graft occlusion. Beneficial effect of ticlopidine on early and late patency rates of venous coronary bypass grafts: a double-blind study. J Thorac Cardiovasc Surg. 1987 Nov;94(5):773–783. [PubMed] [Google Scholar]
  39. Limet R., David J. L., Rigo P. Ticlopidine and coronary surgery. Agents Actions Suppl. 1984;15:188–198. [PubMed] [Google Scholar]
  40. Lorenz R. L., Schacky C. V., Weber M., Meister W., Kotzur J., Reichardt B., Theisen K., Weber P. C. Improved aortocoronary bypass patency by low-dose aspirin (100 mg daily). Effects on platelet aggregation and thromboxane formation. Lancet. 1984 Jun 9;1(8389):1261–1264. doi: 10.1016/s0140-6736(84)92446-2. [DOI] [PubMed] [Google Scholar]
  41. MANTEL N., HAENSZEL W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959 Apr;22(4):719–748. [PubMed] [Google Scholar]
  42. Mahler F., Schneider E., Gallino A., Bollinger A. Combination of suloctidil and anticoagulation in the prevention of reocclusion after femoro-popliteal PTA. Vasa. 1987;16(4):381–385. [PubMed] [Google Scholar]
  43. McCollum C., Alexander C., Kenchington G., Franks P. J., Greenhalgh R. Antiplatelet drugs in femoropopliteal vein bypasses: a multicenter trial. J Vasc Surg. 1991 Jan;13(1):150–162. [PubMed] [Google Scholar]
  44. Meister W., von Schacky C., Weber M., Lorenz R., Kotzur J., Reichart B., Theisen K., Weber P. C. Low-dose acetylsalicylic acid (100 mg/day) after aortocoronary bypass surgery: a placebo-controlled trial. Br J Clin Pharmacol. 1984 Jun;17(6):703–711. doi: 10.1111/j.1365-2125.1984.tb02407.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Ollivier J. P. Etude de la perméabilité des pontages aortocoronaires à 6 mois. Etude multicentrique française. Arch Mal Coeur Vaiss. 1991 Apr;84(4):537–542. [PubMed] [Google Scholar]
  46. Pantely G. A., Goodnight S. H., Jr, Rahimtoola S. H., Harlan B. J., DeMots H., Calvin L., Rösch J. Failure of antiplatelet and anticoagulant therapy to improve patency of grafts after coronary-artery bypass: a controlled, randomized study. N Engl J Med. 1979 Nov 1;301(18):962–966. doi: 10.1056/NEJM197911013011803. [DOI] [PubMed] [Google Scholar]
  47. Peto R. Why do we need systematic overviews of randomized trials? Stat Med. 1987 Apr-May;6(3):233–244. doi: 10.1002/sim.4780060306. [DOI] [PubMed] [Google Scholar]
  48. Pirk J., Ruzbarský V., König J., Krajícek M., Pavel P., Firt P. The effect of antiaggregating drugs on the patency of grafts in the arterial system. World J Surg. 1980 Sep;4(5):615–619. doi: 10.1007/BF02401646. [DOI] [PubMed] [Google Scholar]
  49. Pirk J., Vojácek J., Kovác J., Fabián J., Firt P. Improved patency of the aortocoronary bypass by antithrombotic drugs. Ann Thorac Surg. 1986 Sep;42(3):312–314. doi: 10.1016/s0003-4975(10)62742-7. [DOI] [PubMed] [Google Scholar]
  50. Rajah S. M., Salter M. C., Donaldson D. R., Subba Rao R., Boyle R. M., Partridge J. B., Watson D. A. Acetylsalicylic acid and dipyridamole improve the early patency of aorta-coronary bypass grafts. A double-blind, placebo-controlled, randomized trial. J Thorac Cardiovasc Surg. 1985 Sep;90(3):373–377. [PubMed] [Google Scholar]
  51. Sanz G., Pajarón A., Alegría E., Coello I., Cardona M., Fournier J. A., Gómez-Recio M., Ruano J., Hidalgo R., Medina A. Prevention of early aortocoronary bypass occlusion by low-dose aspirin and dipyridamole. Grupo Español para el Seguimiento del Injerto Coronario (GESIC) Circulation. 1990 Sep;82(3):765–773. doi: 10.1161/01.cir.82.3.765. [DOI] [PubMed] [Google Scholar]
  52. Sarin S., Shami S. K., Cheatle T. R., Bearn P., Scurr J. H., Coleridge Smith P. D. When do vascular surgeons prescribe antiplatelet therapy? Current attitudes. Eur J Vasc Surg. 1993 Jan;7(1):6–13. doi: 10.1016/s0950-821x(05)80535-3. [DOI] [PubMed] [Google Scholar]
  53. Schoop W. Spätergebnisse bei konservativer Therapie der arteriellen Verschlusskrankheit. Internist (Berl) 1984 Jul;25(7):429–433. [PubMed] [Google Scholar]
  54. Schwartz L., Bourassa M. G., Lespérance J., Aldridge H. E., Kazim F., Salvatori V. A., Henderson M., Bonan R., David P. R. Aspirin and dipyridamole in the prevention of restenosis after percutaneous transluminal coronary angioplasty. N Engl J Med. 1988 Jun 30;318(26):1714–1719. doi: 10.1056/NEJM198806303182603. [DOI] [PubMed] [Google Scholar]
  55. Serruys P. W., Luijten H. E., Beatt K. J., Geuskens R., de Feyter P. J., van den Brand M., Reiber J. H., ten Katen H. J., van Es G. A., Hugenholtz P. G. Incidence of restenosis after successful coronary angioplasty: a time-related phenomenon. A quantitative angiographic study in 342 consecutive patients at 1, 2, 3, and 4 months. Circulation. 1988 Feb;77(2):361–371. doi: 10.1161/01.cir.77.2.361. [DOI] [PubMed] [Google Scholar]
  56. Taylor R. R., Gibbons F. A., Cope G. D., Cumpston G. N., Mews G. C., Luke P. Effects of low-dose aspirin on restenosis after coronary angioplasty. Am J Cardiol. 1991 Oct 1;68(9):874–878. doi: 10.1016/0002-9149(91)90402-7. [DOI] [PubMed] [Google Scholar]
  57. Thaulow E., Frøysaker T., Dale J., Vatne K. Failure of combined acetylsalicylic acid and dipyridamole to prevent occlusion of aortocoronary venous bypass graft. Scand J Thorac Cardiovasc Surg. 1987;21(3):215–220. doi: 10.3109/14017438709106027. [DOI] [PubMed] [Google Scholar]
  58. United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: interim results. UK-TIA Study Group. Br Med J (Clin Res Ed) 1988 Jan 30;296(6618):316–320. [PMC free article] [PubMed] [Google Scholar]
  59. van der Meer J., Hillege H. L., Kootstra G. J., Ascoop C. A., Mulder B. J., Pfisterer M., van Gilst W. H., Lie K. I. Prevention of one-year vein-graft occlusion after aortocoronary-bypass surgery: a comparison of low-dose aspirin, low-dose aspirin plus dipyridamole, and oral anticoagulants. The CABADAS Research Group of the Interuniversity Cardiology Institute of The Netherlands. Lancet. 1993 Jul 31;342(8866):257–264. doi: 10.1016/0140-6736(93)91815-4. [DOI] [PubMed] [Google Scholar]

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