Bleeding complications with new antithrombotics used in ischaemic heart disease

Despite adjunctive therapy with heparin and aspirin, patients undergoing percutaneous transluminal coronary angioplasty (PTCA) continue to be at risk of abrupt vessel closure and acute ischaemic events. In an attempt to overcome the limitations of traditional antithrombotics, more potent agents have been developed, including direct thrombin inhibitors (e.g., hirudin and hirulog) and new antiplatelet agents [e.g., the glycoprotein IIb/IIIa receptor inhibitor c7E3 Fab (ReoProTM)]. Initial phase-III trials of hirudin in patients with acute coronary syndromes identified an excess incidence of major bleeding complications. Some of these trials have been recommenced using lower doses. Reports on phase-III trials of hirulog should be forthcoming soon. Of the new agents, the chimeric monoclonal antibody fragment c7E3 Fab has the most extensive available data. In the phase-III evaluation of 7E3 for the Prevention 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 PTCA. Major bleeding episodes occurred more frequently with this regimen than with placebo, although rates of intracranial haemorrhage or surgery for bleeding did not differ between groups. The findings suggest that the risk of bleeding complications might be reduced, without compromising efficacy, by administering heparin on a weight-adjusted basis in patients treated with c7E3 Fab.