16 THERAPY

Thrombolyti~ in the light of day

Alteplase seems to have a clear, statistically significant circadian pattern of efficacy, reports Dr Peter Kurnik from the US. 1

Thrombolytic therapy with alteplase showed higher efficacy when administered from noon to midnight, as measured by the presence of TIMI 3 patency or grade 4 ordinal variable patency, in a retrospective analysis of data from 692 patients who received alteplase for treatment of acute MI. The magnitude of the observed circadian pattern indicates clinical significance, says Dr Kurnik.

Notably, a subset of 127 patients who received alteplase within 2 hours of onset of symptoms achieved the greatest patency and showed the greatest difference between morning and afternoon efficacy in this study.

Practical impHcations Dr Kurnik's observations add to the evidence that

supports the hypothesis of a hypercoagulable state in the morning, says Dr Eugene Braunwald from Harvard Medical School in Boston, US, in a commentary that accompanies the alteplase study findings.2

In view of these observations, it may be appropriate to adjust the dose of thrombolytic agents according to the time of the day at which patients with acute MI present, as well as to the risk of cerebral haemorrhage. For example, one may consider administering a lower than usual dose to patients at high risk of cerebral haemorrhage (e.g. due to advanced age or hypertension), who present in the afternoon or evening, when thrombi appear to be more responsive to thrombolytic therapy, comments Dr Braunwald.

He points out that a recently developed plasminogen activator (TNK), which is currently being evaluated by the TIMI Study Group, will be of special interest in this context.

1. Kumik PB. Circadian variation in the efficacy of tissue·type plasminogen

activator. Circulation 91: 1341·1346,1 Mar 1995 2. Braunwald E. Morning resistance to thrombolytic therapy. Circulation 91: 1604-1606, 1 Mar 1995

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1 Apr 1995INPHARMA'" 0156-270319510980-000161$01.00° Adlslnternatlonal Limited 1995. All rights reserved