Aspirin and Stroke – a neurologist's viewpoint

Dr Delanty explained that stroke is the third leading cause of death in the developed world. It is the commonest neurological disorder causing permanent disability in adults. He classified them as ischaemic, haemorrhagic, or due to subarachnoid haemorrhage and venous infarction. However, they are not always easily demarcated. Ischaemic strokes can undergo haemorrhagic transformation.

About 90% of strokes are ischaemic. They can be embolic or thrombotic, due to arterial thrombo-occlusive disease. Cardiac embolic stroke is linked to significant atheroma in the aortic arch and carotid arteries. Patients with atrial fibrillation at risk of stroke should have warfarin as their treatment of choice.

The aim of aspirin in avoiding stroke is to prevent platelet aggregation. Arterial thrombotic or embolic mechanisms are secondary to endothelial failure: aspirin inhibits platelet aggregation and should help prevent stroke.

The many secondary prevention trials of aspirin in stroke have had many designs and many doses, and meta-analysis has confirmed the benefit of aspirin 75mg to 325mg per day.

Two studies, TASS (ticlopidine-aspirin,) and CAPRIE (clopidogrel-aspirin) have shown a true treatment effect of aspirin. aspirin reduced myocardial infarctions, strokes, and vascular deaths by approximately 25% in all the high risk patients. TASS showed significant falls in cumulative death and non-fatal strokes in patients with prior transient ischaemic attacks or minor strokes taking either drug. However, ticlopidine is no longer recommended because of its significant risk of neutropenia needing monitoring, and of diarrhoea. It is also, of course, much more expensive.

In CAPRIE, with nearly 20,000 patients, there was a very marginal benefit of clopidogrel over aspirin. Among 1000 patients taking aspirin for a year 19 cardiovascular events would be avoided. The figure for clopidrogel was 24. However, clopidrogel is much more expensive than aspirin, and it has been since linked with platelet problems. There is some controversy about the result of the combined aspirin-dipyridamole study: the relative risk reduction of stroke is better on the two together.

The big concern now, said Dr Delanty was not whether aspirin works – that has been proved. It was that it is greatly under-used. In the Scandinavian 4S trial, only 37% of the patients who should have been taking aspirin actually were being prescribed it. He pleaded with doctors to give aspirin to those at high risk of cardiovascular events – those with hypertension, hyperlipidaemia, smokers, with diabetes, etc.

He also recommended its use in acute non-haemorrhagic stroke. The CAST/IST/MAST-I trials enrolled >40,000 patients to 160mg or 300mg aspirin. One death or stroke was prevented by giving aspirin to each 100 patients with acute stroke. It is recognised as part of the standard care of acute stroke. If given to every acute stroke patient in Ireland, with about 3,000 strokes per year, aspirin would prevent 30 deaths annually. In the United States, with an estimated 750,000 to 1 million strokes per year, the numbers saved would be huge. However, it is important that the aspirin used is not enteric coated, as absorption is too slow and may even be incomplete.