r-hirudin in unstable angina pectoris. Rationale and preliminary data from the APT pilot study.
Therapeutic strategies for patients with unstable angina have been hampered by the difficulty in defining a homogenous cohort of patients, and identifying their risk for subsequent cardiovascular events. Despite the similarities in pathophysiological mechanisms between unstable angina and acute myocardial infarction, an analysis of recent trials of thrombolytic therapy in unstable angina has failed to reveal evidence of improved clinical outcome. However, both aspirin and heparin have shown evidence of benefit and in order to test more specific and potent thrombin inhibitors (for example hirudin) it is necessary to identify a cohort of patients with a high risk of subsequent cardiac events. This small scale pilot study set out to identify patients with unstable angina or non-Q wave infarction with a high risk of subsequent cardiac events, and to undertake a feasibility study of two dose regimens of recombinant hirudin (HPW023). The impact on haemostatic parameters and the need for dose adjustment in order to achieve the target therapeutic range of activated partial thromboplastin time (aPTT) was also assessed. Firstly, the study revealed that it was possible to identify a high risk patient population (6/43, 14% had sustained infarction; 10/43, 23% required emergency or urgent revascularization and 11/43, 26% elective revascularization). Secondly, it was possible to achieve stable antithrombin regimens with the two selected doses of hirudin (at least 78% of patients were within the target range at any of the time points). Haemostatic parameters were compared, but larger scale studies are required to establish safety, with a reliable estimate of the impact of hirudin on clinical events.
Cardiovascular Research Unit, University of Edinburgh.
K A
KA
Fox
D000789:Angina, Unstable / Q000188:drug therapy*; D000991:Antithrombins / Q000627:therapeutic use*; D024764:Hirudin Therapy; D006801:Humans; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000627:therapeutic use
D000991:Antithrombins; D011994:Recombinant Proteins