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
[en] The efficacy of coronary bypass grafting obviously being linked to graft patency, it is compulsory to look for any innovation that could improve the patency rate. Ticlopidine, an antiplatelet drug, was tested against placebo in a double-blind trial: 173 patients (475 grafts) subjected to venous coronary artery bypass grafting were randomly treated with ticlopidine (250 mg twice daily) or placebo from the second postoperative day for 12 months. Graft patency was assessed by digital angiography on days 10 (99.4% of the patients), 180 (98.2%), and 360 (91.7%). The effect of treatment on platelet aggregation and bleeding time were measured concomitantly; a clear-cut effect was demonstrated at each interval. Intention-to-treat graft-by-graft analysis shows that ticlopidine significantly reduced the graft occlusion rate on day 10 (7.1% versus 13.4%, p less than 0.05), day 180 (15.0% versus 24.0%, p less than 0.02), and day 360 (15.9% versus 26.1%, p less than 0.01). Sequential grafts to the left anterior descending coronary artery, with side-to-side anastomosis to diagonal branch(es), are less frequently occluded than individual grafts. On the contrary, grafts to endarterectomized vessels occlude more frequently. Individual patient-by-patient analysis shows that patency of all grafts at each study time, is more frequent in the ticlopidine group. The difference is significant when one considers patients without sequential or endarterectomized grafts. The difference is also present at each study time: day 10 (84.4% versus 66.7%, p less than 0.05), day 180 (74.4% versus 52.3%, p less than 0.05) and day 360 (75.0% versus 52.5%, p less than 0.05). Results are even more impressive if one excludes from analysis the four patients in the ticlopidine group in whom administration of the drug was delayed. This supports previous suggestions that early therapy is necessary. These results show that graft occlusion occurs mainly in the first 6 postoperative months. The incidence of occlusion is significantly reduced by ticlopidine therapy.
Disciplines :
Cardiovascular & respiratory systems Surgery
Author, co-author :
Limet, Raymond ; Université de Liège - ULiège > Département des sciences cliniques > Chirurgie cardio-vasculaire et thoracique
David, Jean-Louis ; Université de Liège - ULiège > Services généraux (Faculté de médecine) > Relations académiques et scientifiques (Médecine)
Magotteaux, Paul ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques
Larock, M. P.
Rigo, Pierre ; Université de Liège - ULiège > Département des sciences de la motricité > Pathologie générale et médecine nucléaire
Language :
English
Title :
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
Bourassa MG Campeau L Lespérance J Grondin CM Changes in grafts and coronary arteries after saphenous vein aortocoronary bypass surgery: results at repeat angiography Circulation 65 Pt 2 1982 II90 II97
Bourassa MG Enjalbert M Campeau L Lespérance J Progression of atherosclerosis in coronary arteries and bypass grafts: ten years later Am J Cardiol 53 1984 102C 107C
Verstraete M Brown BG Chesebro JH Evaluation of antiplatelet agents in the prevention of aorto-coronary bypass occlusion Eur Heart J 7 1986 4 13
Campeau L Enjalbert M Lespérance J 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 311 1984 1329 1332
Baur HR Van Tassel RA Pierach CA Gobel FL Effects of sulfinpyrazone on early graft closure after myocardial revascularization Am J Cardiol 49 1982 420 424
Brown BG Cukingnan RA Goede L Improved graft patency with antiplatelet drugs in patients treated for one year following coronary bypass surgery [Abstract] Am J Cardiol 47 1981 494
Mayer JE Jr Lindsay WG Castaneda W Nicoloff DM Influence of aspirin and dipyridamole on patency of coronary artery bypass grafts Ann Thorac Surg 31 1981 204 210
McEnany MT Salzman EW Mundth ED The effect of antithrombotic therapy on patency rates of saphenous vein coronary artery bypass grafts J T horac C ardiovasc S urg 83 1982 81 89
Pantely GA Goodnight SH Jr Rahimtoola SH Failure of antiplatelet and anticoagulant therapy to improve patency of grafts after coronary-artery bypass: a controlled, randomized study N Engl J Med 301 1979 962 966
Chesebro JR Clements IP Fuster V A platelet-inhibitor-drug trial in coronary-artery bypass operations: benefits of perioperative dipyridamole and aspirin therapy on early postoperative vein-graft patency N Engl J Med 307 1982 73 78
Chesebro JH Fuster V Elveback LR Effect of dipyridamole and aspirin on late vein-graft patency after coronary bypass operations N Engl J Med 310 1984 209 214
Brown BG Cukingnan RA De Rouen T Improved graft patency in patients treated with platelet-inhibiting therapy after coronary bypass surgery Circulation 72 1985 138 146
Lorenz RL Schacky CV Weber M Improved aortocoronary bypass patency by low-dose aspirin (100 mg daily): effects on platelet aggregation and thromboxane formation Lancet 1 1984 1261 1264
Chevigné M David JL Rigo P Limet R Effect of ticlopidine on saphenous vein bypass patency rates: a double-blind study Ann Thorac Surg 37 1984 371 378
David JL Monfort F Herion F Raskinet R Compared effects of three dose-levels of ticlopidine on platelet function in normal subjects Thromb Res 14 1979 35 49
Gensini GF Favilla S Breschi C Abbate R Costanzo G Neri Serneri GG Ticlopidine activity on platelet function in patients with enhanced platelet aggregation: a short-term crossover study Haemostasis 13 1983 294 300
Di Minno G Cerbone AM Mattioli PL Turco S Iovine C Mancini M Functionally thrombasthenic state in normal platelets following the administration of ticlopidine J Clin Invest 75 1985 328 338
Violi F Alessandri C Frattaroli S Ghiselli A Balsano F Effects of ticlopidine on platelet function and blood coagulation Thromb Haemost 48 1982 166 168
Lips JPM Sixma JJ Schiphorst ME The effect of ticlopidine administration to humans on the binding of adenosine diphosphate to blood platelets Thromb Res 17 1980 19 27
Conard J Lecrubier C Scarabin PY Horellou MH Samama M Bousser MG Effects of long term administration of ticlopidine on platelet function and hemostatic variables Thromb Res 20 1980 143 148
Bruno JJ The mechanisms of action of ticlopidine Thromb Res (Suppl IV) 4 1983 59 67
Vallée E Maffrand JP Bernat A Delebassée D Tissinier A Ticlopidine as an experimental antithrombotic agent Agents Actions (Suppl) 15 1984 50 59
Piovella F Ricetti MM Almasio P Samaden A Semino G Ascari E The effect of ticlopidine on human endothelial cells in culture Thromb Res 33 1984 323 332
Ashida SI Ishihara M Ogawa H Abiko Y Protective effect of ticlopidine on experimentally induced peripheral arterial occlusive disease in rats Thromb Res 18 1980 55 67
Gröntoft KC Mulec H Gutierrez A Olander R Thromboprophylactic effect of ticlopidine in arteriovenous fistulas for haemodialysis Scand J Urol Nephrol 19 1985 55 57
Walter P Geroulanos S Rothlin M Turina M Senning A Die rasterelektronenoptische Oberflächenveränderungen der Gefassinnenfläche gewobener Dacron-Gefäs-sprothesen nach Verabreichung von Ticlopidin Folia Angiol 29 1981 20 32
Pumphrey CW Fuster V Dewanjee MK Murphy KP Vlietstra RE Kaye MP A new in vivo model of arterial thrombosis: the effect of administration of ticlopidine and verapamil in dogs Thromb Res 28 1982 663 675
Hayward R Hunter GJS Digital subtraction angiography in coronary artery bypass graft assessment: clinical applicability Br Heart J 54 1985 357 361
Rigo P Bailey IK Griffith LSC Value and limitations of segmental analysis of stress thallium myocardial imaging for localization of coronary artery disease Circulation 61 1980 973 981
Rigo P Reiber HC Dressler J Stress thallium-201 myocardial scintigraphy: review of methodological problems and proposal for standardization Eur Heart J 1 1980 81 87
Mielke CH Kaneshiro TA Mather JM Weiner JM Rapaport SI The standardized Ivy bleeding time and its prolongation by aspirin Blood 34 1969 204 215
Rothlin ME Pfluger N Speiser K Platelet inhibitors versus anticoagulants for prevention of aorto-coronary bypass graft occlusion Eur Heart J 6 1985 168 175
Harker LA Malpass TW Branson HE Hessel EA Slichter SJ Mechanisms of abnormal bleeding in patients undergoing cardiopulmonary bypass: acquired transient platelet dysfunction associated with selective α granule release Blood 56 1980 824 833
Bachmann F McKenna R Cole ER Najafi H The hemostatic mechanism after open-heart surgery. I. Studies on plasma coagulation and fibrinolysis in 512 patients after extracorporeal circulation J T horac C ardiovasc S urg 70 1975 76 85
McKenna R Bachmann F Whittaker B Gilson J Weinberg M The hemostatic mechanism after open-heart surgery. II. Frequency of abnormal platelet functions during and after extracorporeal circulation J T horac C ardiovasc S urg 70 1975 298 308
Larock MP Burguet W Grenade T Thromboendarterectomy in association with bypass surgery: evaluation of results by pre- and post-operative myocardial scintigraphy and angiography Eur Heart J 6 Suppl 1 1985 116
Lipton MJ Takaro T Clayman J Maley T Factors associated with long-term graft patency after coronary artery bypass surgery Prog Cardiovasc Dis 28 1986 301 308
Thebault JJ Blatrix C Blanchard J Panak E Effect of ticlopidine treatment on liver metabolizing enzyme in man Br J Clin Pharmacol 10 1980 311 313
David JL Limet R Levels of platelet reactivity and patency rate of coronary bypass in a Ticlopidine-placebo double blind study Thromb Res 6 1986 141 147
de Gramont A Canuel C Krulik M Toxicité hématologique de la ticlopidine? Nouv Rev Fr Hematol 24 1982 35 37
Biour M Toussaint P Duhamel G Canuel C Krulick M Calmus Y Ticlopidine: atteintes sanguines et hépatiques? Therapie 37 1982 222 224
de Fraiture WH Claas FHJ Meyboom RHB Bijwerkingen van ticlopidine; klinische waarneming en immunologisch onderzoek Ned Tijdschr Geneeskd 126 1982 1051 1054