BLEEDING COMPLICATIONS WITH NEW ANTITHROMBOTICS USED IN ISCHEMIC-HEART-DISEASE

Despite adjunctive therapy with heparin and aspirin, patients undergoi ng percutaneous transluminal coronary angioplasty (PTCA) continue to b e at risk of abrupt vessel closure and acute ischaemic events. In an a ttempt to overcome the limitations of traditional antithrombotics, mor e potent agents have been developed, including direct thrombin inhibit ors (e.g., hirudin and hirulog) and new antiplatelet agents [e.g., the glycoprotein IIb/IIIa receptor inhibitor c7E3 Fab (ReoPro(TM)]. Initi al phase-III trials of hirudin in patients with acute coronary syndrom es identified an excess incidence of major bleeding complications. Som e of these trials have been recommenced using lower doses. Reports on phase-III trials of hirulog should be forthcoming soon. Of the new age nts, the chimeric monoclonal antibody fragment c7E3 Fab has the most e xtensive available data. In the phase-III evaluation of 7E3 for the Pr evention of Ischemic Complications trial, the administration of a c7E3 Fab bolus plus c7E3 Fab infusion reduced the rate of major ischaemic events by 35% at 30 days (p=0.008) in patients undergoing high-risk PT CA. Major bleeding episodes occurred more frequently with this regimen than with placebo, although rates of intracranial haemorrhage or surg ery for bleeding did not differ between groups. The findings suggest t hat the risk of bleeding complications might be reduced, without compr omising efficacy, by administering heparin on a weight-adjusted basis in patients treated with c7E3 Fab.