Heparin and Low-Molecular-Weight Heparin

The clinical benefit of coronary-artery stenting performed in conjunction with coronary angioplasty is limited by the risk of thrombotic occlusion of the stent as well as hemorrhagic and vascular complications of intensive anticoagulation. We compared antiplatelet therapy with conventional anticoagulant therapy with respect to clinical outcomes 30 days after coronary-artery stenting. After successful placement of Palmaz-Schatz coronary-artery stents, 257 patients were randomly assigned to receive antiplatelet therapy (ticlopidine plus aspirin) and 260 to receive anticoagulant therapy (intravenous heparin, phenprocoumon, and aspirin). The primary cardiac end point was a composite measure reflecting death from cardiac causes or the occurrence of myocardial infarction, aortocoronary bypass surgery, or repeat angioplasty. The primary noncardiac end point comprised death from noncardiac causes, cerebrovascular accident, severe hemorrhage, and peripheral vascular events. Of the patients assigned to antiplatelet therapy, 1.6 percent reached a primary cardiac end point, as did 6.2 percent of those assigned to anticoagulant therapy (relative risk, 0.25; 95 percent confidence interval, 0.06 to 0.77). With antiplatelet therapy, there was an 82 percent lower risk of myocardial infarction than in the anticoagulant-therapy group, and a 78 percent lower need for repeat interventions. Occlusion of the stented vessel occurred in 0.8 percent of the antiplatelet-therapy group and in 5.4 percent of the anticoagulant-therapy group (relative risk, 0.14; 95 percent confidence interval, 0.02 to 0.62). A primary noncardiac end point was reached by 1.2 percent of the antiplatelet-therapy group and 12.3 percent of the anticoagulant-therapy group (relative risk, 0.09; 95 percent confidence interval, 0.02 to 0.31). Hemorrhagic complications occurred only in the anticoagulant-therapy group (in 6.5 percent). An 87 percent reduction in the risk of peripheral vascular events was observed with antiplatelet therapy. As compared with conventional anticoagulant therapy, combined antiplatelet therapy after the placement of coronary-artery stents reduces the incidence of both cardiac events and hemorrhagic and vascular complications.

Platelets are believed to play a part in the ischemic complications of coronary angioplasty, such as abrupt closure of the coronary vessel during or soon after the procedure. Accordingly, we evaluated the effect of a chimeric monoclonal-antibody Fab fragment (c7E3 Fab) directed against the platelet glycoprotein IIb/IIIa receptor, in patients undergoing angioplasty who were at high risk for ischemic complications. This receptor is the final common pathway for platelet aggregation. In a prospective, randomized, double-blind trial, 2099 patients treated at 56 centers received a bolus and an infusion of placebo, a bolus of c7E3 Fab and an infusion of placebo, or a bolus and an infusion of c7E3 Fab. They were scheduled to undergo coronary angioplasty or atherectomy in high-risk clinical situations involving severe unstable angina, evolving acute myocardial infarction, or high-risk coronary morphologic characteristics. The primary study end point consisted of any of the following: death, nonfatal myocardial infarction, unplanned surgical revascularization, unplanned repeat percutaneous procedure, unplanned implantation of a coronary stent, or insertion of an intraaortic balloon pump for refractory ischemia. The numbers of end-point events were tabulated for 30 days after randomization. As compared with placebo, the c7E3 Fab bolus and infusion resulted in a 35 percent reduction in the rate of the primary end point (12.8 vs. 8.3 percent, P = 0.008), whereas a 10 percent reduction was observed with the c7E3 Fab bolus alone (12.8 vs. 11.5 percent, P = 0.43). The reduction in the number of events with the c7E3 Fab bolus and infusion was consistent across the end points of unplanned revascularization procedures and nonfatal myocardial infarction. Bleeding episodes and transfusions were more frequent in the group given the c7E3 Fab bolus and infusion than in the other two groups. Ischemic complications of coronary angioplasty and atherectomy were reduced with a monoclonal antibody directed against the platelet IIb/IIIa glycoprotein receptor, although the risk of bleeding was increased.

Blockade of the platelet glycoprotein IIb/IIIa receptor with abciximab (a monoclonal-antibody Fab fragment directed against the receptor) has been shown to diminish ischemic complications among patients undergoing high-risk coronary angioplasty or directional atherectomy but increases bleeding complications. The widespread applicability of this treatment is unknown, particularly in view of the observed risk of hemorrhage. In a prospective, double-blind trial, we randomly assigned patients undergoing urgent or elective percutaneous coronary revascularization at 69 centers to receive abciximab with standard-dose, weight-adjusted heparin (initial bolus of 100 U per kilogram of body weight); abciximab with low-dose, weight-adjusted heparin (initial bolus of 70 U per kilogram); or placebo with standard-dose, weight-adjusted heparin. The primary efficacy end point was death from any cause, myocardial infarction, or urgent revascularization within 30 days of randomization. The trial was terminated at the first interim analysis, with 2792 of the planned 4800 patients enrolled. At 30 days, the composite event rate was 11.7 percent in the group assigned to placebo with standard-dose heparin; 5.2 percent in the group assigned to abciximab with low-dose heparin (hazard ratio, 0.43; 95 percent confidence interval, 0.30 to 0.60; P<0.001); and 5.4 percent in the group assigned to abciximab with standard-dose heparin (hazard ratio, 0.45; 95 percent confidence interval, 0.32 to 0.63; P<0.001). There were no significant differences among the groups in the risk of major bleeding, although minor bleeding was more frequent among patients receiving abciximab with standard-dose heparin. Inhibition of the platelet glycoprotein IIb/IIIa receptor with abciximab, together with low-dose, weight-adjusted heparin, markedly reduces the risk of acute ischemic complications in patients undergoing percutaneous coronary revascularization, without increasing the risk of hemorrhage.