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Summary Background Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. Funding British Heart Foundation.

Objective To determine the effects of low dose aspirin on cognitive function in middle aged to elderly men and women at moderately increased cardiovascular risk. Design Randomised double blind placebo controlled trial. Setting Central Scotland. Participants 3350 men and women aged over 50 participating in the aspirin for asymptomatic atherosclerosis trial. Intervention Low dose aspirin (100 mg daily) or placebo for five years. Main outcome measures Tests of memory, executive function, non-verbal reasoning, mental flexibility, and information processing five years after randomisation, with scores used to create a summary cognitive score (general factor). Results At baseline, mean vocabulary scores (an indicator of previous cognitive ability) were similar in the aspirin (30.9, SD 4.7) and placebo (31.1, SD 4.7) groups. In the primary intention to treat analysis, there was no significant difference at follow-up between the groups in the proportion achieving over the median general factor cognitive score (32.7% and 34.8% respectively, odds ratio 0.91, 95% confidence interval 0.79 to 1.05, P=0.20) or in mean scores on the individual cognitive tests. There were also no significant differences in change in cognitive ability over the five years in a subset of 504 who underwent detailed cognitive testing at baseline. Conclusion Low dose aspirin does not affect cognitive function in middle aged to elderly people at increased cardiovascular risk. Trial registration ISRCTN 66587262.

Forty-seven patients presenting with symptoms of large middle cerebral artery territory infarcts were studied prospectively using serial CT brain scanning to assess infarct extent and swelling, and transcranial Doppler ultrasound to assess middle cerebral artery patency. The single most important determinant of cerebral infarct swelling was the extent of the infarct: the larger the infarct, the greater the amount of swelling (Spearman Rank correlation coefficient 0.74, p < 0.0001). In addition, if the blood velocity in the symptomatic middle cerebral artery did not increase in the first 5 days after symptom onset (implying no early reperfusion) the odds of severe infarct swelling were increased 7.6-fold (95% confidence interval 1.2- to 46.4-fold, 2p = 0.03), and the odds of a poor clinical outcome (dead or dependent in activities of daily living at 3 months) were increased 10-fold (95% confidence interval 2.7- to 41.6-fold, 2p = 0.0007). The only patients who recovered sufficiently to be able to return home by 3 months after stroke were amongst those whose symptomatic middle cerebral artery blood velocity increased (either spontaneously or associated with fibrinolytic or antithrombotic therapy) in the first 5 days after stroke. We conclude that early reperfusion is not associated with a worsening of acute cerebral infarct swelling, and may lead to a better clinical outcome.