Anticoagulant properties, clinical efficacy and safety of efegatran, a direct thrombin inhibitor, in patients with unstable angina

Aims Thrombin plays a key role in the clinical syndrome of unstable angina. We investigated the safety and efficacy of five dose levels of efegatran s ulphate, a direct thrombin inhibitor, compared to heparin in patients with unstable angina. Methods Four hundred and thirty-two patients with unstable angina were enro lled. Five dose levels of efegatran were studied sequentially, ranging from 0.105 mg. kg(-1).h(-1) to 1.2 mg. kg(-1). h(-1) over 48 h. Safety was asse ssed clinically, with reference to bleeding and by measuring clinical labor atory parameters. Efficacy was assessed by the number of patients experienc ing any episode of recurrent ischaemia as measured by computer-assisted con tinuous ECG ischaemia monitoring. Clinical end-points were: episodes of rec urrent angina, myocardial infarction, coronary intervention (PTCA or CABG), and death. Results Efegatran demonstrated dose dependent ex-vivo anticoagulant activit y with the highest dose level of 1.2 mg.kg(-1).h(-1) resulting in steady st ate mean activated partial thromboplastin time values of approximately thre e times baseline. Thrombin time was also increased. Neither of the efegatra n doses studied were able to suppress myocardial ischaemia during continuou s ECG ischaemia monitoring to a greater extent than that seen with heparin. There were no statistically significant differences in clinical outcome or major bleeding between the efegatran and heparin groups. Minor bleeding an d thrombophlebitis occurred more frequently in the efegatran treated patien ts. Conclusion Administration of efegatran sulphate at levels of at least 0.63 mg. kg(-1).h(-1) provided an antithrombotic effect which is at least compar able to an activated partial thromboplastin time adjusted heparin infusion. There was no excess of major bleeding. The level of thrombin inhibition by efegatran, as measured by activated partial thromboplastin time, appeared to be more stable than with heparin. Thus, like other thrombin inhibitors, efegatran sulphate is easier to administer than heparin. However, no clinic al benefits of efegatran over heparin were apparent.