First chronic platelet glycoprotein IIb/IIIa integrin blockade. A randomized, placebo-controlled pilot study of xemilofiban in unstable angina with percutaneous coronary interventions.
BACKGROUND
Clinical studies have demonstrated the efficacy of intravenous administration of agents that block platelet glycoprotein IIb/IIIa receptors in the setting of percutaneous coronary revascularization. Although the optimal duration of treatment has not been determined, more prolonged receptor blockade has been associated with increased efficacy. Orally active glycoprotein IIb/IIIa receptor antagonists may be advantageous and required for chronic therapy.


RESULTS
Thirty patients with unstable angina who were undergoing percutaneous coronary interventions were randomized to placebo or Xemilofiban 35 mg orally before and 20 to 25 mg TID for 30 days after angioplasty. Bleeding events, platelet aggregation, and pharmacokinetic and hematologic parameters were assessed during hospitalization and at 2 and 4 weeks after drug initiation. Xemilofiban produced a rapid, sustained, marked inhibition of platelet aggregation. ADP-induced platelet aggregation at 2 hours after the initial dose at 2 and 4 weeks was 15%, 8%, and 11% in the Xemilofiban group compared with 80%, 68%, and 69% in the placebo group. Among 20 patients randomized to Xemilofiban there was 1 death after emergency coronary bypass surgery complicated by severe bleeding diathesis, and 3 patients had major bleeding events. Patients on Xemilofiban for 30 days reported episodes of mild mucocutaneous bleeding.


CONCLUSIONS
Xemilofiban, an orally active glycoprotein IIb/ IIIa receptor inhibitor, produced rapid, sustained, extensive inhibition of platelet aggregation for a period of up to 30 days. At the dose initially tested, however, acute major bleeding and mucocutaneous bleeding during chronic administration were encountered.
Simpfendorfer
C
C
Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195, USA.
Kottke-Marchant
K
K
Lowrie
M
M
Anders
R J
RJ
Burns
D M
DM
Miller
D P
DP
Cove
C S
CS
DeFranco
A C
AC
Ellis
S G
SG
Moliterno
D J
DJ
Raymond
R E
RE
Sutton
J M
JM
Topol
E J
EJ
D000328:Adult; D000368:Aged; D000789:Angina, Unstable / Q000150:complications / Q000188:drug therapy*; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage; D001550:Benzamidines; D001026:Coronary Artery Bypass / Q000009:adverse effects; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D010979:Platelet Function Tests; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*
D001550:Benzamidines; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C091295:xemilofiban; D001241:Aspirin