Prevention of stroke: risk stratification and targeted and novel therapies

Stroke is a common disorder with dire consequences for the patient and for society and will increase in prevalence over the coming years. Following stroke, many patients unfortunately suffer a further stroke, and recurrent strokes account for approximately 25% of the total. Considerable scope therefore exists to improve both primary and secondary stroke prevention. This thesis has addressed several areas at key stages in the prevention of stroke by developing strategies to better identify those at highest risk, attempting to better target pre-existing anti-platelet therapy and by beginning the evaluation of xanthine oxidase reduction and uric acid lowering therapy in the prevention of stroke. A clinical scoring system to aid diagnostic recognition in those with suspected transient ischaemic attack (TIA) was successfully developed and has the ability to reduce the referral of those without cerebrovascular disease to busy TIA clinics. The score was developed on data from 3216 patients and included 9 clinically useful predictive variables. After adjustment to reflect the greater seriousness of missing true TIA patients, 97% of TIA and 22% of non-TIA patients were accurately identified. The results were confirmed during prospective validation. Use of the score could have a substantial effect on waiting times for assessment; there is potential double the numbers seen within the timeframe recommended by guidelines with no other change to services. This would be an important advance given the recent evidence that rapid assessment and treatment of those with TIA greatly reduces stroke risk. Aspirin resistance was found to be higher in those with cerebrovascular microembolic signals (MES) and carotid disease compared to those with equivalent carotid disease and no MES. This study included sixty-two patients who mostly had symptomatic carotid disease. Approximately a quarter had MES. The rate of aspirin resistance on at least one test was 25.8% (16 patients), with 13 (21%) re