CONTENTS
Yale University
School of Medicine
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Platelet Effects of GP llb/llla Antagonists
in Patients Undergoing Coronary Artery
Bypass Grafting
Although there has been reluctance to initiate GP llb/llla antagonists in patients undergoing CABG, clinical data supports their use in this setting and suggests that they may have a protective effect on platelets during extracorporeal circulation, prompting quicker recovery of platelet function following bypass surgery. Platelet counts typically decrease by 30-40% after cardiopulmonary bypass as a result of platelet aggregation and destruction during cardiopulmonary bypass. By inhibiting this process, fibrinogen receptor antagonists may reduce the degree of thrombocytopenia and improve qualitative platelet function after bypass surgery. If platelets were "anesthetized" during cardiopulmonary bypass, as described by Edmunds in 1978, postoperative platelet dysfunction may improve.
In the PRISM-Plus trial [1], a 30% reduction in death or MI (at 30 days) was observed in patients who were treated with tirofiban and heparin compared to patients who subsequently underwent CABG (Fig. 1).
Fig. 1. PRISM-Plus trial.
N Engl J Med 1998; 338: 1488-97.
For patients who underwent CABG within 24 hours of cessation of tirofiban, the incidence of TIMI major bleeding was comparable to heparin alone (17.2% with tirofiban plus heparin versus 35.4% with heparin alone).
In the PURSUIT study [2], there was no difference in the incidence of major bleeding in patients who underwent bypass surgery whether patients received placebo or eptifibatide (8.2% in each of the treatment groups). Furthermore, there was a significant 45% reduction in the combined clinical endpoint of death or MI within 30 days in patients undergoing CABG who were treated with GP IIb/IIIa inhibition versus placebo (18% vs. 33%). (Fig. 2).
Fig. 2. Death or MI within 30 days in patients undergoing CABG within 72 hours of presentation of an acute coronary syndrome.
N Engl J Med 1998; 339: 436-443.
In the subgroup of patients (n=78) who underwent CABG surgery within 2 hours of receiving eptifibatide, there was no difference of major bleeding or need for platelet transfusion compared to placebo (Table 1). Interestingly, only 7% of patients treated with GP llb/llla inhibition prior to bypass experienced a >50% reduction in platelets, whereas 16% of patients in the placebo group did so.
Table 1. Patients undergoing CABG within 2 hours of GP IIb/IIIa blocker therapy.
N Engl J Med 1998; 339: 436-443.
In conclusion, short-acting GP llb/llla blocker therapy does not appear to result in an increased risk of bleeding among patients undergoing CABG surgery within 2 hours of discontinuing therapy.
1. The Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators: Inhibition of the Platelet Glycoprotein IIb/IIIa receptor with Tirofiban in Unstable Angina and Non-Q-Wave Myocardial Infarction. N Engl J Med, 1998 338: 1488-1497.
2. The PURSUIT Trial Investigators: Inhibition of Platelet Glycoprotein IIb/IIIa with Eptifibatide in Patients With Acute Coronary Syndromes. N Engl J. Med 1998; 339: 436-443.
Last modified: October 14, 1999 (PL)
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