Randomized comparison of direct thrombin inhibition versus heparin in conjunction with fibrinolytic therapy for acute myocardial infarction: results from the GUSTO-IIb Trial. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO-IIb) Investigators.
OBJECTIVE
We sought to show that hirudin might interact differently with streptokinase (SK) and tissue-type plasminogen activator (t-PA), which could reduce the incidence of death or reinfarction at 30 days.


BACKGROUND
In a large-scale trial of patients with acute coronary syndromes, hirudin provided modest benefit compared with heparin. However, the interaction with thrombolytic agents was not specifically assessed.


METHODS
Patients with symptoms of acute myocardial infarction and electrocardiographic ST segment elevation were treated with thrombolytic therapy and randomly assigned to receive hirudin or heparin.


RESULTS
A total of 2,274 patients received t-PA, and 1,015 received SK. Baseline characteristics were balanced by antithrombin assignment. Among SK-treated patients, death or reinfarction at 30 days occurred more often in those treated with adjunctive heparin (14.4%) rather than hirudin (8.6%, odds ratio [OR] 1.78, 95% confidence interval [CI] 1.20 to 2.66, p = 0.004). Among t-PA-treated patients, the rates were 10.9% with heparin and 10.3% with hirudin (OR 1.06, 95% CI 0.81 to 1.38, p = 0.68; for treatment heterogeneity: chi-square 4.20, degrees of freedom [df] 1, p = 0.04). After adjustment for baseline differences between thrombolytic groups, the rates were 9.1% for SK with hirudin, 10.3% for t-PA with hirudin, 10.5% for t-PA with heparin and 14.9% for SK with heparin (for treatment heterogeneity: chi-square 4.5, df 1, p = 0.03), suggesting that the beneficial treatment effect of hirudin was limited to the SK-treated patients.


CONCLUSIONS
Hirudin interacts favorably with SK but not t-PA, highlighting the importance of thrombin activity after SK therapy and the potential for simulating the effects of a more potent fibrinolytic agent through direct antithrombin therapy.
Metz
B K
BK
Cleveland Clinic Foundation, Ohio 44195, USA.
White
H D
HD
Granger
C B
CB
Simes
R J
RJ
Armstrong
P W
PW
Hirsh
J
J
Fuster
V
V
MacAulay
C M
CM
Califf
R M
RM
Topol
E J
EJ
D000368:Aged; D000991:Antithrombins / Q000008:administration & dosage / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use; D024764:Hirudin Therapy; D006629:Hirudins / Q000008:administration & dosage; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D010960:Plasminogen Activators / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D013300:Streptokinase / Q000008:administration & dosage / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome
D000991:Antithrombins; D005343:Fibrinolytic Agents; D006629:Hirudins; D006493:Heparin; D013300:Streptokinase; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator