Platelet IIb/IIIa Antagonist for the Reduction of Acute coronary syndrome events in a Global Organization Network - PARAGON B
This randomized, double blind, placebo controlled trial compared 30 day outcomes between patients treated with the GP IIb/IIIa inhibitor lamifiban plus standard therapy compared to standard therapy alone in the setting of ACS without persistent ST elevation.
Patients treated with lamifiban would have a 25% reduction in the 30 day primary composite endpoint compared with placebo patients.
Patients Enrolled: 5225
Mean Follow Up: 30 day for composite; 1 year for death
Mean Patient Age: >=21 years
Hospitalized for ACS; Age >=21 years; >=1 episode of cardiac ischemic pain at rest lasting >=10 minutes <12 hours before randomization; and one of the following (1) tansient or persisent ST segment depression >0.5 mm, transient ST segment elevation >0.5mm, or definite T wave inverion or (2) CK-MB, troponin T or troponin I >ULN
active bleeding; impaired hemostatsis; increased bleeding risk; contraindication to aspirin or heparin; planned fibrinolysis or GP IIb/IIIa inhibition; GP IIb/IIIa inhibition within 1 week; LBBB or pacemaker use; estimated creatinine clearance <30 mL/min; serious comorbid disease likely to limit survival; current enrollment in trials of other investigational drugs or devices
30 day composite of death, MI, or severe recurrent ischemia
30 day composite of death or MI 30 day individual endpoints of death, MI, and severe recurrent ischemia 7 day triple composite 7 day composite of death or MI 6 month composite of death or MI 1 year death
Lamifiban IV (500 ug bolus + <=72 hour infusion) plus standard heparin and aspirin therapy vs placebo plus standard therapy of heparin and aspirin. Lamifiban infusion dose was titrated to achieve a target plasma lamifiban concentration between 18 and 42 ng/mL and was adjusted for renal function. IV unfractionated heparin dosing was 5000 U bolus + 1000 U/h infusion for pts weighing >80 kg and 60 U/kg bolus + 12 U/kg/h infusion for pts weighing <=80 kg. Asprin dosing was 150-325 mg at enrollment and daily thereafter.
The primary end point of death, MI or severe recurrent ischemia occurred in 11.8% of lamifiban-treated patients and in 12.8% of placebo-treated patients by 30 days (OR, 0.914; 95% CI, 0.769 to 1.087; P=0.329). Kaplan Meier curves showed no difference in death or MI rates by 6 months (14% in lamifiban-treated patients vs 15% in placebo-treated patients, p=0.28). Treatment effect did not differ significantly by the performance or timing of PCI. Intermediate bleeding was more common in lamifiban-treated patients (14.0% vs 11.5%, p=0.002), but intracranial hemorrhage and thrombocytopenia were not increased. In a prosepective subgroup analysis among patients troponin positive at baseline, lamifiban was associated with a significant reduction in the primary endpoint (from 19.4% to 11.0%, p=0.01). No treatment effect was seen in troponin negative patients (11.2% vs 10.8%, p=0.86).
Lamifiban did not significantly effect clinical outcomes in patients with non–ST-elevation acute coronary syndromes treated with concomitant heparin and aspirin, despite titration to targeted plasma concentrations. This was unlike PARAGON-A, where a significant relation was seen between plasma concentrations and outcomes. Treatment benefit with lamifiban was observed in patients who were troponin-positive at enrollment, indicating its effect may differ in higher risk populations.
Circulation 2002;105:316-321. (main results) Circulation 2001;103:2891-2896. (Troponin substudy)
Keywords: Acute Coronary Syndrome, Intracranial Hemorrhages, Platelet Aggregation Inhibitors, Troponin I, Heparin, Troponin T, Tyrosine, Thrombocytopenia, Platelet Glycoprotein GPIIb-IIIa Complex
< Back to Listings