Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization.

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

[1]  E. Topol,et al.  Peripheral vascular complications after conventional and complex percutaneous coronary interventional procedures. , 1992, The American journal of cardiology.

[2]  R. Califf,et al.  Characteristics and consequences of myocardial infarction after percutaneous coronary intervention: insights from the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT). , 1995, Journal of the American College of Cardiology.

[3]  E J Topol,et al.  Economic assessment of platelet glycoprotein IIb/IIIa inhibition for prevention of ischemic complications of high-risk coronary angioplasty. EPIC Investigators. , 1996, Circulation.

[4]  R. Califf,et al.  Bleeding complications with the chimeric antibody to platelet glycoprotein IIb/IIIa integrin in patients undergoing percutaneous coronary intervention. EPIC Investigators. , 1995, Circulation.

[5]  E F Cook,et al.  Identification and preliminary validation of predictors of major bleeding in hospitalized patients starting anticoagulant therapy. , 1987, The American journal of medicine.

[6]  A. Jaffe,et al.  Thrombolysis in myocardial infarction (TIMI) trial—Phase I: Hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase , 1988 .

[7]  T. Kreulen,et al.  The relationship of anticoagulation level and complications after successful percutaneous transluminal coronary angioplasty. , 1992, American heart journal.

[8]  J. Ferguson,et al.  The use of activated clotting times to monitor heparin therapy during and after interventional procedures , 1994, Clinical cardiology.

[9]  E. Topol,et al.  Significance of mild transient release of creatine kinase-MB fraction after percutaneous coronary interventions. , 1996, Circulation.

[10]  R. Califf,et al.  Post-intervention cardiac enzyme elevations: Prognostic significance in IMPACT II , 1996 .

[11]  W. O’Neill,et al.  Randomized prospective evaluation of prolonged versus abbreviated intravenous heparin therapy after coronary angioplasty. , 1994, Journal of the American College of Cardiology.

[12]  R. Califf,et al.  Relation between activated clotting time during angioplasty and abrupt closure. , 1996, Circulation.

[13]  M. Leon,et al.  Predictors of late mortality following ablative new-device angioplasty in native coronary arteries , 1996 .

[14]  Epic Investigators,et al.  Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. , 1994, The New England journal of medicine.

[15]  R. Califf,et al.  Standard versus low-dose weight-adjusted heparin in patients treated with the platelet glycoprotein IIb/IIIa receptor antibody fragment abciximab (c7E3 Fab) during percutaneous coronary revascularization. PROLOG Investigators. , 1997, The American journal of cardiology.

[16]  L. Parise,et al.  LA Fitzgerald The platelet membrane glycoprotein IIb-IIIa complex , 1988 .

[17]  C. Gaos,et al.  Activated clotting times and activated partial thromboplastin times in patients undergoing coronary angioplasty who receive bolus doses of heparin. , 1992, Catheterization and cardiovascular diagnosis.

[18]  R. Califf,et al.  Randomised trial of coronary intervention with antibody against platelet IIb/IIIa iritegrin for reduction of clinical restenosis: results at six months , 1994, The Lancet.

[19]  P. Esente,et al.  Peripheral vascular complications of coronary angioplasty by the femoral and brachial techniques. , 1994, Catheterization and cardiovascular diagnosis.

[20]  L. Hillis,et al.  Percutaneous transluminal coronary angioplasty. , 1994, The American journal of the medical sciences.