title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA. jang.ik@mgh.harvard.edu
authors.forename: I K
authors.initials: IK
authors.lastname: Jang
authors.forename: D F
authors.initials: DF
authors.lastname: Brown
authors.forename: R P
authors.initials: RP
authors.lastname: Giugliano
authors.forename: H V
authors.initials: HV
authors.lastname: Anderson
authors.forename: D
authors.initials: D
authors.lastname: Losordo
authors.forename: J C
authors.initials: JC
authors.lastname: Nicolau
authors.forename: O P
authors.initials: OP
authors.lastname: Dutra
authors.forename: O
authors.initials: O
authors.lastname: Bazzino
authors.forename: V M
authors.initials: VM
authors.lastname: Viamonte
authors.forename: R
authors.initials: R
authors.lastname: Norbady
authors.forename: A S
authors.initials: AS
authors.lastname: Liprandi
authors.forename: T J
authors.initials: TJ
authors.lastname: Massey
authors.forename: R
authors.initials: R
authors.lastname: Dinsmore
authors.forename: R P
authors.initials: RP
authors.lastname: Schwarz
mesh_terms: D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives; D017024:Chemotherapy, Adjuvant; D017023:Coronary Angiography; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy*; D015425:Myocardial Reperfusion; D010875:Pipecolic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D012008:Recurrence; D016037:Single-Blind Method; D013449:Sulfonamides; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010875:Pipecolic Acids; D010975:Platelet Aggregation Inhibitors; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; D010959:Tissue Plasminogen Activator; C031942:argatroban