Recent antiplatelet drug trials in the acute coronary syndromes. Clinical interpretation of PRISM, PRISM-PLUS, PARAGON A and PURSUIT.
This paper reviews the results of 4 recent clinical trials, Platelet Receptor inhibition for Ischaemic Syndrome Management (PRISM), Platelet Receptor inhibition for Ischaemic Syndrome Management in Patients Limited to very Unstable Signs and symptoms (PRISM-PLUS), Platelet IIb/IIIa Antagonist for the Reduction of Acute coronary syndrome events in a Global Organisation Network (PARAGON A), and Platelet IIb/IIIa in Unstable angina Receptor Suppression Using Integrilin Therapy (PURSUIT), that have investigated the use of glycoprotein (GP) IIb/IIIa inhibitors in with non-ST-segment elevation acute coronary syndromes. The PRISM trial randomised 3232 patients with non-ST-elevation acute coronary syndromes to either tirofiban or heparin. Patients receiving tirofiban had a 32% reduction in the likelihood of death, myocardial infarction (MI) or refractory ischaemia at 48 hours and a 36% reduction in death at 30 days (2.3 vs 3.6%, p = 0.02). The PRISM-PLUS trial randomised 1915 patients with severe non-ST-elevation acute coronary syndromes to either tirofiban alone, heparin alone or the combination of tirofiban and heparin. Patients treated with the combination of tirofiban and heparin had a 27% reduction in death or nonfatal MI at 30 days (8.7 vs 11.9%, p = 0.027). The PARAGON A trial randomised 2282 patients with non-ST-elevation acute coronary syndromes to either high or low dose lamifiban, with or without heparin, or heparin alone. There was no reduction in the rate of death at day 30 or nonfatal MI in patients who received lamifiban; however, at 6 months a significant treatment effect was seen in patients who received low dose lamifiban (13.7%, p = 0.02) but not high dose lamifiban (16.4%, p = 0.38) compared with those who received heparin alone (18.1%). The PURSUIT trial randomised 10,948 patients with non-ST-elevation acute coronary syndromes to either eptifibatide or placebo. Patients receiving eptifibatide had a 9.6% relative, and 1.5% absolute, reduction in death or MI at 30 days (15.7 vs 14.2%, p = 0.04). GP IIb/IIIa inhibitors are revolutionising the way we treat patients with atherosclerotic coronary artery disease. The results of these trials demonstrate that the GP IIb/IIIa inhibitors tirofiban, lamifiban, and eptifibatide are beneficial in the non-ST-elevation acute coronary syndrome population. In the future, acute therapy with an intravenous GP IIb/IIIa inhibitor followed by long term administration of an oral GP IIb/IIIa inhibitor may be the cornerstone of the management of patients with acute coronary syndromes.
Alexander
J H
JH
Duke Clinical Research Institute, Durham, North Carolina, USA.
Harrington
R A
RA
D000085:Acetates / Q000627:therapeutic use; D000208:Acute Disease; D000925:Anticoagulants / Q000627:therapeutic use; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D000077542:Eptifibatide; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D010455:Peptides / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D016032:Randomized Controlled Trials as Topic; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000085:Acetates; D000925:Anticoagulants; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D006493:Heparin; C084062:lamifiban; D000077466:Tirofiban; D000077542:Eptifibatide