Bleeding complications with the chimeric antibody to platelet glycoprotein IIb/IIIa integrin in patients undergoing
F V Aguirre1, E J Topol, J J Ferguson
1Division of Cardiology, St. Louis University Health Sciences Center, MO 63110, USA.
Insights
Novel antiplatelet therapy (c7E3 Fab) reduced ischemic complications in percutaneous coronary revascularization but increased bleeding. Risk factors for bleeding include age, female sex, and procedure complexity.
Area of Science:
- Cardiology
- Interventional Cardiology
- Pharmacology
Background:
- Periprocedural bleeding complications of percutaneous coronary revascularization (PCR) with novel antiplatelet and antithrombin agents are not well understood.
- The Evaluation of c7E3 Fab in Preventing Ischemic Complications of High-Risk Angioplasty (EPIC) trial investigated the use of aspirin, heparin, and c7E3 Fab in 2099 patients undergoing PCR.
- While c7E3 Fab reduced ischemic events, it was associated with increased bleeding complications, necessitating a review of these events and associated risk factors.
Purpose of the Study:
- To review bleeding complications associated with periprocedural use of c7E3 Fab during high-risk angioplasty.
- To identify clinical and procedural variables associated with increased bleeding complications in the EPIC trial.
- To evaluate the safety and efficacy of c7E3 Fab in reducing ischemic complications while assessing bleeding risks.
Main Methods:
- A randomized trial involving 2099 patients undergoing high-risk percutaneous coronary revascularization.
- Patients received aspirin and heparin, plus either placebo or c7E3 Fab (bolus or bolus plus infusion).
- Bleeding complications were assessed by transfusions, hemoglobin decrease, and a combined index; multivariable regression identified risk factors.
Main Results:
- Major bleeding complications occurred more frequently with c7E3 Fab (8.6% bolus, 10.6% bolus+infusion) compared to placebo (3.3%), with most bleeding at the femoral access site.
- Blood product transfusions were higher in the c7E3 Fab groups (14.0%, 16.8%) versus placebo (7.5%).
- Independent predictors of bleeding included older age, female sex, lower weight, c7E3 Fab therapy, and longer/more complex procedures.
Conclusions:
- Bleeding complications were 2-3 times more frequent with c7E3 Fab but were generally transient and well-tolerated.
- Risk-factor analysis and optimization of antithrombotic/antiplatelet strategies may mitigate bleeding risks.
- c7E3 Fab demonstrated significant benefit in reducing ischemic complications and restenosis during PCR.
Background:
The potential for novel antiplatelet and antithrombin agents to contribute to periprocedural bleeding complications of percutaneous coronary revascularization is poorly defined. In the Evaluation of c7E3 Fab in Preventing Ischemic Complications of High-Risk Angioplasty (EPIC) trial, the periprocedural use of aspirin, heparin, and a chimeric antibody to the platelet glycoprotein IIb/IIIa integrin c7E3 Fab in 2099 patients significantly reduced postprocedural ischemic complications and 6-month clinical restenosis but was associated with increased procedural bleeding complications. We review these complications and describe clinical and procedural variables associated with increased bleeding complications in the EPIC trial.
Methods And Results:
Patients with high-risk clinical or lesion morphological characteristics were randomized to receive placebo bolus plus placebo infusion, c7E3 Fab bolus plus placebo infusion, or c7E3 Fab bolus plus c7E3 Fab infusion. Patients received periprocedural aspirin and intravenous heparin continued for a minimum of 12 hours after the procedure. Outcomes reflecting bleeding complications were measured: transfusions, decreased hemoglobin, and an index including both parameters. Major bleeding complications unrelated to bypass surgery occurred in 3.3%, 8.6%, and 10.6%, and blood product transfusions were used in 7.5%, 14.0%, and 16.8% of patients treated with placebo, bolus c7E3 Fab, and bolus plus infusion c7E3 Fab, respectively (both P < .001). Most major bleeding complications occurred at the femoral access site, regardless of treatment. Intracranial hemorrhage (0.3%) and death (0.09%) attributable to major bleeding complications were rare. Multivariable regression analyses identified several variables significantly and independently related to major bleeding complications or greater blood loss, including greater age, female sex, lower weight, c7E3 Fab therapy, and duration and complexity of the index procedure. Major bleeding complications and blood loss in patients receiving bolus plus infusion were not significantly greater than in those receiving bolus alone (P = .38 and P = .14, respectively).
Conclusions:
Bleeding complications unrelated to bypass surgery were two to three times more frequent in patients receiving c7E3 Fab than in those receiving placebo, but most were transient and well tolerated. Risk-factor analysis and modification of concomitant antithrombotic and antiplatelet treatment strategies may aid in reducing bleeding complications and enhancing clinical benefit in patients receiving c7E3 Fab during percutaneous coronary revascularization.
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