Hirudin (desirudin) and Hirulog (bivalirudin) in acute ischaemic syndromes and the rationale for the Hirulog/Early Reperfusion Occlusion (HERO-2) Study.
Unlike unfractionated heparin, direct thrombin inhibitors such as hirudin and Hirulog inhibit clot-bound as well as fluid-phase thrombin, escape neutralisation by platelet secretion products, do not require monitoring, and are unassociated with immune thrombocytopenia. They have been shown to have modest advantages over heparin when given after thrombolytic therapy, reducing reinfarction by 14%. In the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO 2b) trial, patients treated with streptokinase and adjunctive hirudin had a reduction in death or myocardial infarction of 40% at 30 days (8.6% with hirudin versus 14.4% with heparin, p = 0.004). In the Hirulog Early Reperfusion/Occlusion (HERO 1) trial, 48% of patients who received Hirulog as adjunctive therapy with streptokinase had Thrombolysis in Myocardial Infarction (TIMI) trial grade 3 flow in the infarct-related artery, compared with 35% of patients who received heparin with streptokinase (p < 0.05). The HERO 2 study, involving 17,000 patients, will test the hypothesis that Hirulog and aspirin given before streptokinase will reduce mortality compared with aspirin plus heparin. Early administration of direct thrombin inhibitors may potentially improve the outcome of patients treated with thrombolytic therapy.
Green Lane Hospital, Auckland, New Zealand.
H D
HD
White
C J
CJ
Ellis
J K
JK
French
P
P
Aylward
D000368:Aged; D000991:Antithrombins / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use; D024764:Hirudin Therapy; D006629:Hirudins / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D010446:Peptide Fragments / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013300:Streptokinase / Q000627:therapeutic use; D015912:Thrombolytic Therapy
D000991:Antithrombins; D005343:Fibrinolytic Agents; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D006493:Heparin; D013300:Streptokinase; D001241:Aspirin; C074619:bivalirudin