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New antithrombotic and antiplatelet treatment
  1. K L Neuhaus
  1. CA der Medizinsche Klinik II, Städt Kliniken, Mönchebergstrasse 41–43, 34125 Kassel, Germany
  1. Dr Neuhaus

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Thrombosis is the key pathological process in both unstable angina and acute myocardial infarction (MI). Treatment directed against the thrombus may consist of thrombolysis by plasminogen activators, thrombin inhibition, or platelet inhibition. Data from the TIMI IIIA and IIIB trials have shown conclusively that in contrast to their proven benefits in acute MI, plasminogen activators make the prognosis worse in unstable angina.1-3 Thrombolytic treatment is therefore contraindicated in unstable angina, but new types of antithrombotic and antiplatelet agents now offer alternatives to heparin and aspirin.

Thrombin inhibitors

Specific thrombin inhibitors directly inhibit thrombin without the need for cofactors such as antithrombin III, and unlike heparin they inhibit both free and clot bound thrombin. In theory, this should result in superior efficacy, but clinical trials to date have failed to show that the theoretical advantages provide better results in practice. A major problem with all direct thrombin inhibitors is that they have a narrow therapeutic window, and at present they do not offer an alternative for unfractionated heparin (UFH) as the standard treatment for unstable angina.

The prototype direct thrombin inhibitor is hirudin, a naturally occurring polypeptide with a plasma half life of about one hour. The majority of clinical trials in this area have compared hirudin with UFH, but early trials in acute MI using hirudin (bolus of 0.4–0.6 mg/kg and infusions of 0.15–0.2 mg/kg/h for 48–96 hours) in conjunction with thrombolytics found that the rate of intracranial haemorrhage was unacceptably high.4-6 In response to these results, the first trial in unstable angina, GUSTO-IIb, used much lower doses of hirudin (bolus of 0.1 mg/kg followed by infusion of 0.1 mg/kg/h).7 However, the results were not very impressive with only a moderate reduction in the rate of death or MI at 30 days.


It is thought that the disappointing results of GUSTO-IIb may have …

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