To RESTART or Not to RESTART- That is The Question

During the European Stroke Organization conference, clinical trial results were presented, including investigation of treatments and outcomes of both ischemic and hemorrhagic stroke.

One of the most remarkable and surprising results were from the RESTART trial1 presented by Professor Rustam Al-Shahi Salman (Twitter @BleedingStroke) from the University of Edinburgh. This randomized open label trial was designed to answer the question whether antiplatelet medications can be safely restarted in patients who survive a recent intracerebral hemorrhage. The study participants were enrolled from 122 hospitals in the UK and included adults who had developed an intracerebral hemorrhage while on an antithrombotic medication for prevention of ischemic vascular disease.1 A total of 537 patients were randomly assigned to either restart or continue to avoid antiplatelet medication and followed for a median of 2 years for a primary outcome of recurrent symptomatic intracerebral hemorrhage.  In the group assigned to restarting antiplatelet medications, 12 of 268 subjects experienced recurrent intracerebral hemorrhage as compared to 23 of 268 in the group assigned to avoid antiplatelets (p=0.06).1 The rates of all major hemorrhage events in the two groups were similar: 7% in the treatment group and 9% in the avoiding group (p=0.27). There was no difference in the rates of occlusive vascular events which were seen at 15% in the treatment group and 14% in the avoiding group (p=0.92).1

Prior evidence suggests that aspirin is beneficial for secondary prevention of ischemic vascular events, notwithstanding a small increase in the risk of intracerebral hemorrhage2. RESTART is the first RCT studying the effects of restarting aspirin in patients with a prior history of ischemic vascular disease and a recent intracerebral hemorrhage. While not statistically significant, the results demonstrate a lower rate of recurrent hemorrhage if antiplatelet medications are resumed for prevention of occlusive vascular disease despite a recent intracerebral hemorrhage. The composite secondary outcome of non-fatal MI, non-fatal stroke or death from a vascular cause was seen at a significantly lower rate in the treatment group (p=0.025) as compared to the antiplatelet avoiding group.2

The reduced risk of recurrent hemorrhage risk is a surprising finding and needs further confirmation. The authors postulate that this can be potentially explained by shared mechanistic pathways between ischemic stroke and intracerebral hemorrhage.

The results from this trial provide reassurance that antiplatelet medications can be safely restarted for secondary ischemic event prophylaxis in patients with a recent intracerebral hemorrhage. There are ongoing clinical trials including RESTART-Fr3 and STAT ICH4 and the results from these would provide more insight into the effects of antiplatelet therapy resumption after an intracerebral hemorrhage.



  1. Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial. Lancet. 2019 May 21. RESTART Collaboration.
  2. Antithrombotic Trialists’ (ATT) Collaboration Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009; 373: 1849-1860. Baigent C, Blackwell L et al.