A multicenter, randomized study of argatroban versus heparin as adjunct to tissue 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 thrombin inhibitor, argatroban, on reperfusion induced by tissue plasminogen activator (TPA) in patients with acute myocardial infarction (AMI). BACKGROUND Thrombin plays a crucial role in thrombosis and thrombolysis. In vitro and...

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Published in:	Journal of the American College of Cardiology Vol. 33; no. 7; pp. 1879 - 1885
Main Authors:	Jang, Ik-Kyung, Brown, David F.M, Giugliano, Robert P, Anderson, H.Vernon, Losordo, Douglas, Nicolau, Jose C, Dutra, Oscar P, Bazzino, Oscar, Viamonte, Victor Molina, Norbady, Roberto, Liprandi, Alvaro Sosa, Massey, Thomas J, Dinsmore, Robert, Schwarz, Richard P
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-06-1999
Subjects:	Adult Chemotherapy, Adjuvant Coronary Angiography Drug Therapy, Combination Female Fibrinolytic Agents - therapeutic use Follow-Up Studies Heparin - administration & dosage Heparin - therapeutic use Humans Male Middle Aged Myocardial Infarction - diagnostic imaging Myocardial Infarction - drug therapy Myocardial Reperfusion Pipecolic Acids - administration & dosage Pipecolic Acids - therapeutic use Platelet Aggregation Inhibitors - administration & dosage Platelet Aggregation Inhibitors - therapeutic use Recurrence Single-Blind Method Thrombolytic Therapy Tissue Plasminogen Activator - therapeutic use Treatment Outcome CHF cTFC aPTT TPA TIMI PTCA GUSTO Trial MINT Trial CABG MI AMI CPK
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Summary:	OBJECTIVES This study examined the effect of a small-molecule, direct thrombin inhibitor, argatroban, on reperfusion induced by tissue plasminogen activator (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 heparin 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 randomized to heparin, low-dose argatroban or high-dose argatroban in addition to TPA. The primary end point was the rate of thrombolysis in myocardial infarction (TIMI) grade 3 flow at 90 min. RESULTS TIMI grade 3 flow was achieved in 42.1% of heparin, 56.8% of low-dose argatroban (p = 0.20 vs. heparin) and 58.7% of high-dose argatroban patients (p = 0.13 vs. heparin). In patients presenting after 3 h, TIMI grade 3 flow was significantly more frequent in high-dose argatroban versus heparin patients: 57.1% versus 20.0% (p = 0.03 vs. heparin). Major bleeding was observed 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 myocardial infarction, cardiogenic shock or congestive heart failure, revascularization 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 reperfusion with TPA in patients with AMI, particularly in those patients with delayed presentation. The incidences of major bleeding and adverse clinical outcome were lower in the patients receiving argatroban.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 ObjectType-News-3 content type line 23
ISSN:	0735-1097 1558-3597
DOI:	10.1016/S0735-1097(99)00107-2