Surprising findings from the 'RESTART' study suggest that resuming pre-existing platelet inhibitor therapy (compared to avoiding it) may reduce the risk of recurrent symptomatic intracerebral hemorrhages.
Physicians tend to underestimate the risks of medical intervention and overestimate the benefits (reference 1). However, one common exception appears to be the situation following intracerebral hemorrhage: According to observational data, the risk of relapse with platelet aggregation inhibitors in patients with intracerebral hemorrhage with microbleeding is significantly overestimated (reference 2). In about one in four patients with intracerebral hemorrhage, there is a premedication with platelet inhibitors - therefore, more certainty in the decision making for relaunching such therapy would be clinically highly relevant. This was the subject of a recent article in Lancet Neurology (reference 3).
In the 'RESTART'-study (reference 4) 537 survivors of intracerebral hemorrhage under therapy with thrombocyte aggregation inhibitors were randomized to a continuation or pause of intracerebral hemorrhage and followed up for 2 years. The risk of recurrence of intracerebral hemorrhage varied little between the groups (4.9% at re-start versus 9.1% at pause; p = 0.06) - however, patients who resumed platelet inhibitor therapy had a lower risk of ischemic and hemorrhagic apoplexy (although the difference did not reach statistical significance).
A subgroup analysis (reference 2) examined 254 patients who had received an MRI prior to randomization and came to the following conclusion: patients with cerebral microbleeding or superficial siderosis did not appear to have a higher risk of recurrence of bleeding from the restart of platelet inhibition. Also, the number of microbleedings did not seem to influence the risk.
RESTART' is the first randomized study on this problem and further (and above all: statistically better-powered) investigations are necessary - especially as the results contrast with data from previous observational studies. So far, an increased risk of recurrent intracerebral hemorrhage was assumed due to the resumption of thrombocyte aggregation inhibition. Previous studies estimated the highest risk for patients with cerebral microbleeding. Therefore, the data should be surprising for many stroke specialists and need to be further validated. Oral anticoagulants, for which a similar debate is underway, also require data from randomized clinical trials.
If, for example, the data from the ongoing randomized trials 'RESTART' and 'STATICH' are confirmed, this could mean that we may be less restrictive in prescribing thrombocyte aggregation inhibitors in patients with smaller intracerebral hemorrhages and that the MRI result is not necessarily the first decision support.
References:
1. Hoffmann, T. C. & Del Mar, C. Clinicians' Expectations of the Benefits and Harms of Treatments, Screening, and Tests: A Systematic Review. JAMA Intern Med 177, 407-419 (2017).
2. Salman, R. A.-S. et al. Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial. The Lancet Neurology 18, 643-652 (2019).
3. Christensen, H. Antiplatelets after intracerebral haemorrhage: treat the patient, not the brain imaging. The Lancet Neurology 18, 617-619 (2019).
4. Salman, R. A.-S. et al. Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial. The Lancet 393, 2613-2623 (2019).