BACKGROUND: Excessive platelet deposition at the site of arterial damage due to coronary angioplasty plays an important role in the pathophysiology of both abrupt closure and restenosis after that procedure. Even aspirin, a relatively weak platelet antagonist, decreases the complications of coronary angioplasty. This study was designed to provide preliminary safety and efficacy data on the use of a much more powerful antiplatelet agent, m7E3 Fab, a prototype murine monoclonal antibody fragment that binds directly to the platelet glycoprotein IIb/IIIa receptor mediating aggregation in patients undergoing coronary angioplasty. METHODS:Twenty-three patients referred for elective coronary angioplasty who met prespecified criteria designed tominimize risk of bleeding received, in groups of four to six patients, escalating bolus doses of 0.15 to 0.35 mg/kg of this agent immediately before coronary angioplasty. Heparin was administered in the usual manner, but aspirin was withheld for 24 hours before coronary angioplasty and until bleeding times and platelet aggregation had returned to normal after angioplasty. Glycoprotein IIb/IIIa binding site occupation, platelet aggregation response to 20 microM of adenosine diphosphate, and data on bleeding times were acquired at baseline and at 2, 6, 24, 48 and 72 hours after m7E3 Fab administration. Clinical safety and efficacy were also monitored throughout the time of hospitalization, and delayed antimurine immune responses were assayed. Five similar patients received aspirin (325 mg orally per day) but otherwise received the same treatment, thus serving as controls. RESULTS: Treatment with m7E3 Fab resulted in a dose-dependent occupation of binding sites to a maximum of 93% at 2 hours in the highest-dose groups, with an associated graded inhibition of platelet aggregation and increase in bleeding time significantly exceeding that seen in control patients, with a gradual recovery over 6 to 48 hours. Percutaneous transluminal coronary angioplasty was successfully performed in 18 of 21 patients (86%) in whom it was attempted. Arterial and venous sheath removal 24 hours after m7E3 Fab dosing was largely uneventful. No thrombotic complications were seen, and only one patient (excluding a patient who underwent uneventful urgent bypass surgery) had bleeding severe enough to require packed red cell transfusion. Eight patients (36%) developed late antibody titers against m7E3 Fab. CONCLUSIONS: This murine monoclonal antibody provides potent antiaggregatory action and thus may be useful in preventing thrombotic complications of coronary angioplasty, but studies of its safety and efficacy during longer infusions and with larger numbers of patients are needed. Less immunogenic forms of the antibody may be more clinically useful.
RCT Entities:
BACKGROUND: Excessive platelet deposition at the site of arterial damage due to coronary angioplasty plays an important role in the pathophysiology of both abrupt closure and restenosis after that procedure. Even aspirin, a relatively weak platelet antagonist, decreases the complications of coronary angioplasty. This study was designed to provide preliminary safety and efficacy data on the use of a much more powerful antiplatelet agent, m7E3 Fab, a prototype murine monoclonal antibody fragment that binds directly to the platelet glycoprotein IIb/IIIa receptor mediating aggregation in patients undergoing coronary angioplasty. METHODS: Twenty-three patients referred for elective coronary angioplasty who met prespecified criteria designed to minimize risk of bleeding received, in groups of four to six patients, escalating bolus doses of 0.15 to 0.35 mg/kg of this agent immediately before coronary angioplasty. Heparin was administered in the usual manner, but aspirin was withheld for 24 hours before coronary angioplasty and until bleeding times and platelet aggregation had returned to normal after angioplasty. Glycoprotein IIb/IIIa binding site occupation, platelet aggregation response to 20 microM of adenosine diphosphate, and data on bleeding times were acquired at baseline and at 2, 6, 24, 48 and 72 hours after m7E3 Fab administration. Clinical safety and efficacy were also monitored throughout the time of hospitalization, and delayed antimurine immune responses were assayed. Five similar patients received aspirin (325 mg orally per day) but otherwise received the same treatment, thus serving as controls. RESULTS: Treatment with m7E3 Fab resulted in a dose-dependent occupation of binding sites to a maximum of 93% at 2 hours in the highest-dose groups, with an associated graded inhibition of platelet aggregation and increase in bleeding time significantly exceeding that seen in control patients, with a gradual recovery over 6 to 48 hours. Percutaneous transluminal coronary angioplasty was successfully performed in 18 of 21 patients (86%) in whom it was attempted. Arterial and venous sheath removal 24 hours after m7E3 Fab dosing was largely uneventful. No thrombotic complications were seen, and only one patient (excluding a patient who underwent uneventful urgent bypass surgery) had bleeding severe enough to require packed red cell transfusion. Eight patients (36%) developed late antibody titers against m7E3 Fab. CONCLUSIONS: This murine monoclonal antibody provides potent antiaggregatory action and thus may be useful in preventing thrombotic complications of coronary angioplasty, but studies of its safety and efficacy during longer infusions and with larger numbers of patients are needed. Less immunogenic forms of the antibody may be more clinically useful.