Patient-specific dosing of IIb/IIIa antagonists during acute coronary syndromes: rationale and design of the PARAGON B study. The PARAGON B International Steering Committee.
BACKGROUND
Acute coronary syndromes, the leading cause of hospitalizations among adults, are frequently the sequelae of atherothrombotic events associated with coronary arterial plaque rupture. Beyond the usual antithrombotic therapies (aspirin and heparin), potent antiplatelet agents, glycoprotein IIb/IIIa receptor antagonists, have been shown to improve patient outcome. Lamifiban is a short-acting, renally excreted IIb/IIIa antagonist that was found in post hoc analyses of the Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON A) study to reduce the 30-day incidence of death or myocardial infarction by 40% when plasma concentrations of 18 to 42 ng/mL were achieved.


RESULTS
To determine if lamifiban, dosed according to creatinine clearance, could decrease the rates of death, myocardial infarction, or refractory ischemia, a randomized, double-blind, placebo-controlled trial was undertaken. In 26 countries, 5228 patients seen within 12 hours of symptom onset of a non-ST-elevation acute coronary syndrome were randomly assigned to placebo or lamifiban bolus and infusion.


CONCLUSIONS
The plasma concentration of small-molecule IIb/IIIa inhibitors is strongly influenced by renal function, and renal-specific dosing of these agents may improve outcome among patients with acute coronary syndromes. The PARAGON B trial is testing this hypothesis.
Moliterno
D J
DJ
Department of Cardiology and C (Cleveland Clinic Cardiovascular Coordinating Center), The Cleveland Clinic Foundation, Cleveland, OH 44195, USA. molited@ccf.org
D000085:Acetates / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D009204:Myocardial Revascularization; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D015996:Survival Rate; D014443:Tyrosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
D000085:Acetates; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; C084062:lamifiban