A multicenter, randomized study of argatroban versus heparin as adjunct totissue plasminogen activator (TPA) in acute myocardial infarction: Myocardial infarction with novastan and TPA (MINT) study

OBJECTIVES This study examined the effect of a small-molecule, direct throm bin inhibitor, argatroban, on reperfusion induced by tissue plasminogen act ivator (TPA) in patients with acute myocardial infarction (AMI). BACKGROUND Thrombin plays a crucial role in thrombosis and thrombolysis. In vitro and in vivo studies have shown that argatroban has advantages over h eparin for the inhibition of clot-bound thrombin and for the enhancement of thrombolysis with TPA. METHODS One hundred and twenty-five patients with AMI within 6 h were rando mized to heparin, low-dose argatroban or high-dose argatroban in addition t o TPA. The primary end point was the rate of thrombolysis in myocardial inf arction (TIMI) grade 3 flow at 90 min. RESULTS TIMI grade 3 flow was achieved in 42.1% of heparin, 56.8% of low-do se argatroban (p = 0.20 vs. heparin) and 58.7% of high-dose argatroban pati ents (p = 0.13 vs. heparin). In patients presenting after 3 h, TIMI grade 3 flow was significantly more frequent in high-dose argatroban versus hepari n patients: 57.1% versus 20.0% (p = 0.03 vs, heparin). Major bleeding was o bserved in 10.0% of heparin, and in 2.6% and 4.3% of low-dose and high-dose argatroban patients, respectively. The composite of death, recurrent myoca rdial infarction, cardiogenic shock or congestive heart failure, revascular ization and recurrent ischemia at 30 days occurred in 37.5% of heparin, 32. 0% of low-dose argatroban and 25.5% of high-dose argatroban patients (p = 0 .23). CONCLUSIONS Argatroban, as compared with heparin, appears to enhance reperf usion with TPA in patients with AMI, particularly in those patients with de layed presentation. The incidences of major bleeding and adverse clinical o utcome were lower in the patients receiving argatroban. (C) 1999 by the Ame rican College of Cardiology.