title: A prospective, randomized trial comparing combination half-dose tissue-type plasminogen activator and streptokinase with full-dose tissue-type plasminogen activator. Kentucky Acute Myocardial Infarction Trial (KAMIT) Group.
abstract: BACKGROUND
  The potential benefits of combination thrombolytic agents in the treatment of myocardial infarction remain uncertain. In a small pilot study, we demonstrated that combining half-dose tissue-type plasminogen activator (t-PA) with streptokinase (SK) achieved a high rate of infarct vessel patency and a low rate of reocclusion at half the cost of full-dose t-PA.
  
  
  RESULTS
  We designed a prospective trial in which 216 patients were randomized within 6 hours of myocardial infarction to receive either the combination of half-dose (50 mg) t-PA with streptokinase (1.5 MU) during 1 hour or to the conventional dose of t-PA (100 mg) during 3 hours. Acute patency was determined by angiography at 90 minutes, and angioplasty was reserved for failed thrombolysis. Heparin and aspirin regimens were maintained until follow-up catheterization at day 7. Acute patency was significantly greater after t-PA/SK (79%) than with t-PA alone (64%, p less than 0.05). After angioplasty for failed thrombolysis, acute patency increased to 96% in both groups. Marked depletion of serum fibrinogen levels occurred after t-PA/SK compared with t-PA alone at 4 hours (37 +/- 36 versus 199 +/- 66 mg/dl, p less than 0.0001) and persisted 24 hours after therapy (153 +/- 66 versus 252 +/- 75 mg/dl, p less than 0.0001). Reocclusion (3% versus 10%, p = 0.06), reinfarction (0% versus 4%, p less than 0.05), and need for emergency bypass surgery (1% versus 6%, p = 0.05) tended to be less in the t-PA/SK group. Greater myocardial salvage was apparent in the t-PA/SK group as assessed by infarct zone function at day 7 (-1.9 SD/chord versus -2.3 SD/chord after t-PA alone, p less than 0.05). In-hospital mortality (6% versus 4%) and serious bleeding (12% versus 11%) were similar between the two groups.
  
  
  CONCLUSIONS
  These results suggest that a less expensive regimen of half-dose t-PA with SK yields superior 90-minute patency and left ventricular function and a trend toward reduced reocclusion compared with the conventional dose of t-PA.
authors.affiliation: Department of Medicine, University of Kentucky, Lexington.
authors.forename: C L
authors.initials: CL
authors.lastname: Grines
authors.forename: S E
authors.initials: SE
authors.lastname: Nissen
authors.forename: D C
authors.initials: DC
authors.lastname: Booth
authors.forename: J C
authors.initials: JC
authors.lastname: Gurley
authors.forename: N
authors.initials: N
authors.lastname: Chelliah
authors.forename: R
authors.initials: R
authors.lastname: Wolf
authors.forename: J
authors.initials: J
authors.lastname: Blankenship
authors.forename: M C
authors.initials: MC
authors.lastname: Branco
authors.forename: K
authors.initials: K
authors.lastname: Bennett
authors.forename: A N
authors.initials: AN
authors.lastname: DeMaria
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003327:Coronary Disease / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D011446:Prospective Studies; D012008:Recurrence; D013300:Streptokinase / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D014654:Vascular Patency
chemical_list: D004338:Drug Combinations; D013300:Streptokinase; D010959:Tissue Plasminogen Activator