Bivalirudin With Planned or Provisional Abciximab
Background: The direct thrombin inhibitor bivalirudin has previously been associated with better efficacy and lower hemorrhage risk than heparin during balloon angioplasty. This agent has not yet been tested with stenting or in combination with platelet glycoprotein IIb/IIIa antagonists.
Methods and Results: In a pilot trial, 268 patients who underwent coronary intervention were randomized in 3 sequential phases to treatment with bivalirudin (with or without abciximab) or the control regimen of low-dose weight-adjusted heparin with abciximab. Patients in the bivalirudin arms received bivalirudin (1.0 mg/kg bolus, infusion of 2.5 mg/kg/h for 4 hours) plus abciximab in phase A, bivalirudin (0.5 mg/kg bolus, infusion of 1.75 mg/kg/h for the procedure duration) plus provisional ("rescue") abciximab in phase B, or bivalirudin (0.75 mg/kg bolus, infusion of 1.75 mg/kg/h for the procedure duration) plus provisional abciximab in phase C. Abciximab was necessitated on a provisional basis in 24% of the patients in the bivalirudin arms of phases B and C. A composite clinical endpoint of death, myocardial infarction, repeat revascularization, or major bleeding by 7 days occurred in 3.3%, 5.9%, 0, and 10.6% of the patients in the bivalirudin phase A, bivalirudin phase B, bivalirudin phase C, and heparin plus planned abciximab arms, respectively (P = .018 for the pooled bivalirudin groups versus the heparin group).
Conclusion: Bivalirudin with planned or provisional abciximab may be at least as safe and effective as low-dose heparin plus abciximab during percutaneous coronary intervention.

Aspirin and heparin are routinely used during percutaneous coronary revascularization procedures to reduce the incidence rate of thrombotic complications. Considerable additional clinical benefit is achieved with platelet glycoprotein IIb/IIIa receptor antagonists, but these agents are not used in many eligible patients, in part because of cost considerations and the perception that bleeding risk may be increased. Moreover, glycoprotein IIb/IIIa inhibitors are often used in an unplanned fashion, as "rescue" for suboptimal results or procedural ischemic complications. Although such provisional use of glycoprotein IIb/IIIa blockade may be effective, this approach has never been tested in a prospective controlled trial and may be associated with higher bleeding rates.

The direct thrombin inhibitor bivalirudin (hirulog, Angiomax, The Medicines Company, Cambridge, Mass) has recently been approved for clinical use as an alternative to heparin during percutaneous coronary revascularization, primarily on the basis of the results of the Bivalirudin Angioplasty Trial carried out between 1993 and 1994. In that study, ischemic events were reduced by 22% and hemorrhagic complications by 62% with bivalirudin compared with heparin among 4312 patients with unstable angina who underwent balloon angioplasty. These findings suggest that bivalirudin may be particularly well suited to the current practice of planned or provisional glycoprotein IIb/IIIa blockade during coronary intervention, with the potential to better suppress ischemic events when used alone rather than heparin and to limit the risk of bleeding should a glycoprotein IIb/IIIa inhibitor be necessary. No clinical data exist, however, regarding the feasibility of combining glycoprotein IIb/IIIa blockade with a direct thrombin inhibitor, nor has bivalirudin been evaluated in the contemporary era of elective coronary stenting.

This randomized pilot study therefore was performed to assess in a preliminary manner the safety and effectiveness of bivalirudin with planned or provisional administration of abciximab (ReoPro, Centocor, Malvern, Pa), compared with the current efficacy standard regimen of abciximab with low-dose weight-adjusted heparin during percutaneous coronary revascularization. Sequential phases were planned, first focusing on safety (bleeding risk) of bivalirudin combined with abciximab and subsequently assessing the efficacy of bivalirudin alone, with abciximab given only as needed, in suppressing ischemic complications.