PLATELETS AND VASCULAR OCCLUSION Role of platelets and platelet inhibitors in aortocoronary artery vein-graft disease

To study the prevention of occlusion of aortocoronary-artery bypass grafts, we conducted a prospective, randomized, double-blind trial comparing long-term administration of dipyridamole (begun 2 days before operation) plus aspirin (begun 7 hr after operation) with placebo in 407 patients. Results at 1 month and at 1 year showed a reduction in the rate of graft occlusion in patients receiving dipyridamole and aspirin. On the basis of our clinical trial and our experimental studies in dogs and pigs, we describe four consecutive phases of aortocoronary artery bypass vein-graft disease: (1) an early postoperative phase of platelet thrombotic occlusion, which' is significantly prevented by platelet inhibitor therapy when started in the perioperative period; in addition, occlusion rates are presently decreasing, perhaps related to better surgical and technical experience; (2) an intermediate phase of platelet-related intimal hyperplasia, within the first postoperative year, which is not prevented with platelet inhibitor therapy; (3) a late phase of occlusion, toward the end of the first postoperative year, in which intimal hyperplasia or complicating platelet thrombi superimposed on the intimal hyperplasia may contribute to occlusion; platelet inhibitor therapy is of significant benefit in the prevention of this thrombotic type of occlusion; (4) a phase of atherosclerotic disease, after the first postoperative year, in which the role of platelets and of platelet inhibitor therapy is under investigation. Circulation 73, No. 2, 227-232, 1986. CORONARY VEIN-GRAFT DISEASE is an important contributor to the morbidity after coronary artery bypass surgery. It may be responsible for return of angina pectoris, myocardial infarction, and compromised left ventricular function. ' The natural history of vein-graft disease, its pathogenesis, and its prevention with drug therapy have been illuminated by recent experimental and clinical studies. Natural history of vein-graft disease (figure 1). Coronary vein grafts may be individual, sequential, or branched Y and are usually placed in three or more arteries. Hence, in interpreting data on the natural history of vein-graft disease, occlusion rates should be specifically expressed per distal anastomosis, per graft, or per patient, and this is not always stated. Another difficulty is that studies of consecutive patients are needed for accurate determination of occlusion rates, but such From the Division of Cardiology, Mount Sinai Medical Center, New York, and the Division of Cardiovascular Disease and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN. Supported in part by research grants from the NHLBI (HL 17430, HL 21533, HL 23550) and the United States Public Health Service (CRCRR585). Address for correspondence: Valentin Fuster, M.D., Division of Cardiology, Mount Sinai Hospital, One Gustave L. Levy Place, New York, NY 10029. Presented in part at the Workshop on Coronary Artery Bypass Graft Surgery, NHLBI, Bethesda, September 1984. Circulation 72 (suppl V), 1985. Vol. 73, No. 2, February 1986 studies are few. There is a wide variation also in occlusion rates, depending on time after operation and risk factors for occlusion. Early phase of occlusion. Cumulative overall risk of occlusion per distal anastomosis is greatest during the first year and increases more slowly thereafter. The postoperative occlusion rate at one month is 8% to 18%.2-' The occlusion rate per patient, with one or more distal anastomosis occluded, in the same period ranges from 21% to 38%.27 11 Analysis of risk factors for early occlusion is essential in drug trials, since randomization does not ensure equality of treatment groups, and therapy should be analyzed in subsets at equal risk. In our study,2 two important risk factors that increased the early occlusion rate of bypass grafts were low vein-graft blood flow and a small luminal size of the grafted artery (table 1); such factors mainly result from decreased distal runoff or severe arterial disease. Other risk factors of vein-graft occlusion are endarterectomy, bypass to the left circumflex or right coronary artery, local atheromas at the arteriotomy site, or extension of the arteriotomy into a branch vessel, postoperative elevated serum lipids, and smoking.2 12, 13 Currently, there is an overall impression that the early postoperative occlusion rates are decreasing, perhaps related to 227 by gest on Sptem er 5, 2017 http://ciajournals.org/ D ow nladed from