The RESTART trial, published in JAMA Neurology, investigated the long-term effects of resuming antiplatelet therapy in patients who previously experienced intracerebral hemorrhage (ICH) while on antithrombotic medications. This multicenter, randomized clinical trial followed 537 participants over a median of three years to assess whether restarting antiplatelet therapy would lead to increased risks of recurrent hemorrhage or other vascular events. The trial included patients who had discontinued their antithrombotic therapy post-ICH and were then randomized to either resume or avoid antiplatelet therapy. The study's goal was to provide clarity on whether the benefits of restarting antiplatelet therapy in preventing major vascular events would outweigh potential risks associated with recurrent ICH.

The findings from the RESTART trial indicated no statistically significant difference in recurrent ICH between those who restarted antiplatelet therapy and those who did not. Specifically, the rate of recurrent ICH was 8.2% in the antiplatelet therapy group compared to 9.3% in the non-antiplatelet group, which was not a significant difference. Additionally, the trial observed fewer major vascular events in the group taking antiplatelet therapy compared to the group avoiding it, suggesting a potential protective effect against such events. However, these differences were also not statistically significant, indicating that resuming antiplatelet therapy did not result in a major increase in either recurrent bleeding or vascular complications.

A key element of the trial was its design, which ensured minimized selection bias through centralized randomization and incorporated blinded adjudication of outcomes. The trial was conducted across 122 hospitals in the UK, which allowed for a diverse patient population reflective of real-world clinical scenarios. Extended follow-up was achieved for up to seven years for some patients, providing a robust dataset for evaluating the long-term safety of antiplatelet therapy post-ICH. This extended follow-up phase reinforced the trial's initial findings, as adherence remained high, and no notable increase in adverse events or significant changes in patient outcomes were observed over time.

The RESTART trial is noteworthy as it remains the only randomized clinical trial focusing on the effects of antiplatelet therapy in patients with a history of ICH. Its findings offer valuable insights for clinicians considering antiplatelet therapy in similar patient populations, especially those with cardiovascular risks requiring secondary prevention strategies. While the results provide reassurance about the relative safety of resuming antiplatelet therapy, they also underscore the need for further research, particularly in larger patient populations, to fully understand the risks and benefits in specific subgroups and across diverse healthcare settings.