title: Mechanism of benefit of combination thrombolytic therapy for acute myocardial infarction: a quantitative angiographic and hematologic study.
abstract: OBJECTIVE
  The goal of this study was to lend insight into the mechanisms responsible for the beneficial effects of combination thrombolytic therapy.
  
  
  BACKGROUND
  Combination thrombolytic therapy for acute myocardial infarction has been associated with less reocclusion and fewer in-hospital clinical events than has monotherapy.
  
  
  METHODS
  Infarct-related quantitative coronary dimensions and hemostatic protein levels were evaluated in 287 patients with acute myocardial infarction during the early (90-min) and convalescent (7-day) phases after administration of recombinant tissue-type plasminogen activator (rt-PA), urokinase or combination rt-PA and urokinase.
  
  
  RESULTS
  Minimal lumen diameter was similar in the 90-min and 7-day phases after treatment with rt-PA, urokinase and combination rt-PA and urokinase (0.72 +/- 0.45 mm, 0.62 +/- 0.53 mm and 0.75 +/- 0.58 mm, respectively, at 90 min, p = 0.16; and 1.05 +/- 0.56 mm, 1.12 +/- 0.72 mm and 0.94 +/- 0.54 mm, respectively, at 7 days, p = 0.22). In-hospital clinical event and reocclusion rates were less frequent in patients receiving combination therapy than in those receiving monotherapy (25% vs. 38% and 32% for rt-PA and urokinase, respectively, p = 0.084; and 3% vs. 13% and 9% for rt-PA and urokinase, respectively, p = 0.03), but these events were unrelated to early or late coronary dimensions. Patients receiving combination therapy or urokinase monotherapy had significantly higher peak fibrin degradation products (1,307 +/- 860 and 1,285 +/- 898 micrograms/ml vs. 435 +/- 717 micrograms/ml, respectively, p < 0.0001) and lower nadir fibrinogen levels (0.85 +/- 1.00 and 0.75 +/- 0.53 g/liter vs. 1.90 +/- 0.86 g/liter, respectively, p < 0.0001) than did those receiving rt-PA monotherapy. Peak fibrinogen degradation products indirectly correlated (p = 0.004) and baseline (p = 0.026) and nadir (p = 0.089) fibrinogen levels directly correlated with reocclusion.
  
  
  CONCLUSIONS
  Lower in-hospital clinical event and reocclusion rates observed with combination thrombolytic therapy may relate to systemic hematologic factors rather than to the residual lumen obstruction after thrombolysis.
authors.affiliation: Department of Internal Medicine (Cardiology Division), University of Michigan Medical Center, Ann Arbor.
authors.forename: J J
authors.initials: JJ
authors.lastname: Popma
authors.forename: R M
authors.initials: RM
authors.lastname: Califf
authors.forename: S G
authors.initials: SG
authors.lastname: Ellis
authors.forename: B S
authors.initials: BS
authors.lastname: George
authors.forename: D J
authors.initials: DJ
authors.lastname: Kereiakes
authors.forename: J K
authors.initials: JK
authors.lastname: Samaha
authors.forename: S J
authors.initials: SJ
authors.lastname: Worley
authors.forename: J L
authors.initials: JL
authors.lastname: Anderson
authors.forename: D
authors.initials: D
authors.lastname: Stump
authors.forename: L
authors.initials: L
authors.lastname: Woodlief
mesh_terms: D001798:Blood Proteins / Q000032:analysis; D006328:Cardiac Catheterization; D016009:Chi-Square Distribution; D002932:Cineangiography; D017023:Coronary Angiography; D004359:Drug Therapy, Combination; D006487:Hemostasis; D006801:Humans; D009203:Myocardial Infarction / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000453:epidemiology; D011994:Recombinant Proteins / Q000627:therapeutic use; D012044:Regression Analysis; D015912:Thrombolytic Therapy / Q000706:statistics & numerical data; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use*; D016277:Ventricular Function, Left
chemical_list: D001798:Blood Proteins; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator