A Platelet-Inhibitor-Drug Trial in Coronary-Artery Bypass Operations: Benefit of Perioperative Dipyridamole and Aspirin Therapy on Early Postoperative Vein-Graft Patency

To prevent occlusion of aortocoronary-artery-bypass grafts, we conducted a prospective, randomized-double-blind trial comparing dipyridamole (instituted two days before operation) plus aspirin (added seven hours after operation) with placebo in 407 patients. Vein-graft angiography was performed in 360 patients (88 per cent) within six months of operation (median, eight days). Within one month of operation, 3 per cent of vein-graft distal anastomoses (10 of 351) were occluded in the treated patients, and 10 per cent (38 of 362) in the placebo group; the proportion of patients with one or more distal anastomoses occluded was 8 per cent (10 of 130) in the treated group and 21 per cent (27 of 130) in the placebo group. This benefit in graft patency persisted in each of over 50 sub-groups. Early postoperative bleeding was similar in the two groups. In this trial dipyridamole and aspirin were effective in preventing graft occlusion early after operation. (N Engl J Med. 1982;307:73–8.), THE patency of aortocoronary-bypass grafts decreases progressively over time and relates directly to improvement in symptoms^{1 2 3} and in left ventricular function.^{3 4 5 6} In the pathophysiology of graft occlusion, there is endothelial damage to the vein, with subsequent platelet deposition to the subendothelial structures.^{7 8 9 10} Mural thrombi can form in vein grafts within a few hours of the operation^{9 11} and can lead to the thrombotic occlusion that occurs early after surgery,⁸,¹¹ suggesting a role for preoperative prevention. Dipyridamole therapy started 48 hours before the operation and aspirin added hours after it have decreased platelet deposition,¹⁰ mural-thrombus formation,⁹ and smooth-muscle-cell intimal proliferation¹² in canine.