‘Early’ and ‘Immediate’ Aspirin

Clearly there is a need for further trials of Aspirin in Primary Prevention, but there are two special situations which represent an extrapolation from the present available evidence, both of which merit consideration.

The first is what has become known as ‘early’ aspirin: that is, aspirin given by a doctor or para-medic on first contact with a patient who has chest pain and is judged to possibly have an MI.

No randomised trial has adequately tested ‘early’ aspirin, yet there is limited encouragement for the measure. ISIS-2 separately randomised aspirin and thrombolytic treatment after infarction in over 17,000 MI patients. (43) The Chinese acute stroke trial (CAST) 38 was based on 21,000 stroke patients. Both these gave evidence suggestive of an increased reduction in mortality by aspirin when given early after the onset of symptoms.

On the other hand, in neither Cardiff aspirin III (44) nor the International Stroke Trial (IST) (39) was there evidence of additional benefit from ‘early’ aspirin.
Despite the lack of direct evidence it has become common practice in the UK for doctors and para-medics to carry aspirin for this use (45) and some Health Authorities and other bodies encourage it.

An extension of this measure is what might be called ‘immediate’ aspirin: that is, aspirin taken by subjects themselves as soon as they experience chest pain. This would necessitate the instruction of older subjects, and those judged for any reason to be at high-risk of a thrombotic event, to carry their own aspirin and chew and swallow a tablet immediately they experience chest pain.

If either ‘early’ or ‘immediate’ aspirin is recommended, then it would seem reasonable to use a soluble form of aspirin (see discussion of Formulations of Aspirin in section 9 below). While aspirin is absorbed quite rapidly from both plain and mouth-dispersible tablets, high levels of plasma aspirin are achieved within minutes of chewing or swallowing a tablet of soluble aspirin. (46) Each of these formulations can be obtained foil-wrapped, ideal for carrying in a coat pocket or a bag.

Further questions arise as to the subjects to whom ‘immediate’ aspirin might be recommended. In particular, should patients who are already on long-term low-dose prophylaxis be so advised? In the absence of evidence from appropriate trials, this has also to be decided on clinical grounds. It would seem not to be unreasonable however to argue that if a thrombus develops despite daily exposure to aspirin, then some sensitive palatelets have come into the circulation and an extra ‘flush’ of aspirin could well be beneficial. In any case, a single dose of 300, or even 600 mg of soluble aspirin, in addition to a daily dose of perhaps 100 mg. is unlikely to do any harm. (47)

A further question about self-administered ‘immediate’ aspirin arises with patients with angina as it would not be advisable for an aspirin tablet to be taken every time a patient experiences anginal pain. A careful explanation to a patient should however avoid this, and in any case most patients seem to be able to distinguish the pain of infarction from exercise induced angina.

There is one further reason why ‘early’ or ‘immediate’ aspirin may be advisable. A high proportion of patients in whom an infarct is proven are likely to go on to receive thrombolytic therapy. A number of studies have given evidence of a ‘marked’ or ’considerable’ heightening of platelet activity after thrombolysis. 48-9 Prior treatment with aspirin is therefore recommended. (50)

It must be stressed however that both these measures, ‘Early’ and ‘Immediate’ Aspirin are untested and they represent an extrapolation from the established benefits of aspirin. Both however seem to be most reasonable expectations. Furthermore, an attraction of the measures is that if chest pain which leads a subject to take a tablet turns out to be only muscular, aspirin will not have been inappropriate, while if the pain does arise from an infarct, ‘immediate’ or ‘early’ aspirin might save life and or disability.