International, randomized, controlled trial of lamifiban (a platelet glycoprotein IIb/IIIa inhibitor), heparin, or both in unstable angina. The PARAGON Investigators. Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network.
BACKGROUND
Unstable angina and non-Q-wave myocardial infarction involve coronary arterial plaque rupture, platelet activation, and thrombus formation. This study tested the benefit of different doses of lamifiban (a platelet IIb/IIIa antagonist) alone and in combination with heparin in patients with these conditions to select the most promising lamifiban regimen for subsequent evaluation.


RESULTS
At 273 hospitals in 20 countries, 2282 patients were randomly assigned to lamifiban (2x2 factorial design: low-dose [1 microg/min] with and without heparin versus high-dose [5 microg/min] with and without heparin) or to standard therapy (placebo and heparin). All patients received aspirin. The composite primary end point of death or nonfatal myocardial infarction at 30 days occurred in 11.7% of those receiving standard therapy, 10.6% receiving low-dose lamifiban, and 12.0% receiving high-dose lamifiban (P=0.668). By 6 months, this composite was lowest for those assigned to low-dose lamifiban (P=0.027) and intermediate for those assigned to high-dose lamifiban (P=0.450) compared with control (13.7%, 16.4%, and 17.9%, respectively). Compared with control, the combination of high-dose lamifiban and heparin resulted in more intermediate or major bleeding (12.1% versus 5.5%; P=0.002) and a similar rate of ischemic events. Conversely, low-dose lamifiban and heparin yielded similar bleeding rates as in the control group but fewer ischemic events at 6 months (12.6% versus 17.9%; P=0.025).


CONCLUSIONS
In unstable angina and non-Q-wave infarction, platelet IIb/IIIa antagonism with lamifiban reduces adverse ischemic events at 6 months beyond that of aspirin and heparin therapy. The role of conjunctive heparin remains uncertain but appears more favorable with low-dose IIb/IIIa antagonism. Larger-scale study is needed to more reliably estimate these effects.
D000085:Acetates / Q000627:therapeutic use*; D000368:Aged; D000789:Angina, Unstable / Q000188:drug therapy* / Q000401:mortality; D000925:Anticoagulants / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D016019:Survival Analysis; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000085:Acetates; D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D006493:Heparin; C084062:lamifiban; D001241:Aspirin