RESTARTing antiplatelet after ICH halves recurrence risk
Restarting antiplatelet therapy in survivors of intracranial haemorrhage (ICH)-related stroke is safe without raising their risk of a recurrent ICH, contrary to the commonly perceived risk of a recurrence with an antithrombotic drug, the RESTART* trial has shown.
While patients who survived an ICH are at risk of haemorrhagic and occlusive vascular events, there has been no direct evidence on whether antiplatelet therapy — which is known to be associated with bleeding risk — can be used safely in this patient population for secondary prevention of vascular disease.
“The results are reassuring for survivors of brain haemorrhage who need to take antiplatelet medicines to prevent heart attacks and strokes,” said principal investigator Professor Rustam Salman from the Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
After a median follow-up of 2 years, the primary outcome of recurrent ICH was seen in 4 percent of patients who restarted antiplatelet therapy compared with 9 percent of those who discontinued the therapy (adjusted hazard ratio [HR], 0.51, 95 percent confidence interval, 0.25–1.03; p=0.06). [Lancet 2019;393:2613-2623]
In addition, the secondary composite outcome of all major haemorrhagic events** also occurred in fewer patients who restarted antiplatelet therapy than those who discontinued (7 percent vs 9 percent, HR, 0.71; p=0.27). The other secondary composite outcome of all major occlusive vascular events*** occurred at a similar rate between the two groups (15 percent vs 14 percent, HR, 1.02; p=0.92).
“Our finding that antiplatelet therapy might have reduced the risk of recurrent ICH was unexpected,” said Salman and co-authors, who suggested that this may be attributed to the reduction of arterial thrombosis and inflammation with antiplatelet therapy, both processes of which can trigger haemorrhage.
“Therefore, starting antiplatelet therapy seems to be safe and might be beneficial in patients who survived a median of 76 days after ICH, most of whom had good functional ability at baseline and a higher probability of good functional outcome at 6-month follow-up,” they added.
Paving way for a robust stroke community effort
The prospective, open-label, multicentre trial randomized 537 patients who had survived an ICH (for a median of 76 days) in a 1:1 ratio to either restart or avoid antiplatelet therapy (choice of antiplatelet therapy was adjudicated by patient’s physician). The participants were already on antiplatelet therapy when they developed ICH, and were followed for up to 5 years.
“Few serious adverse events occurred, which were neither outcomes nor expected complications of stroke,” the investigators reported.
Although the study only enrolled 75 percent (n=537) of the intended population of 720 participants, the results paved the way for future research, according to Drs Wendy Ziai and Alexander Tsiskaridze from The Johns Hopkins University in Baltimore, Maryland and Ivane Javakhishvili Tbilisi State University in Tbilisi, Georgia, US, respectively in an accompanying commentary. [Lancet 2019;393:2567-2569]
“Future studies would benefit from earlier onset of antiplatelet on the basis of the results from RESTART because they suggest that the risk of ICH recurrence with antiplatelet therapy is potentially low,” they commented.
“Although similar treatment effect estimates for the primary outcome in the premedian and postmedian periods after ICH symptom onset do not suggest that the risk is higher in the first 2 months, optimal timing of starting antiplatelet therapy after ICH remains unclear,” Ziai and Tsiskaridze noted.
They also pointed out that antiplatelet therapy is only one out of the many factors that can affect the risk of recurrent ICH, and thus, ongoing studies on the potential interactions between antiplatelet therapy and other factors such as age, hypertension, cerebral microbleeds, cerebral amyloid angiopathy, ethnicity, and apolipoprotein E alleles are warranted.
“We hope that RESTART has started a bigger, more inclusive, and more robust stroke community effort,” they added.
Already, two randomized trials — RESTART-Fr and STATICH — are currently ongoing, and the RESTART investigators have plans to continue follow-up of patients for another 2 years as well as perform a meta-analysis of individual patient data of these trials, which may provide more evidence on the role of antiplatelet therapy on preventing ICH recurrence.