First RCT provides reassurance about the use of antiplatelet therapy after ICH


By Sunalie Silva

7 Sep 2021

Uncertainty about when – or if – to restart antithrombotic therapy in patients who have survived intracerebral haemorrhage (ICH) may be clearer after extended follow up data from the first RCT to investigate the dilemma, suggests its reintroduction is safe and has no statically significant effect on risk of recurrent ICH.

The UK trial of 537 adults, randomly assigned to restart antiplatelet therapy (oral aspirin, dipyridamole or clopidogrel) or to avoid it, is the first RCT to investigate the long-term effects of antiplatelet drug use among ICH survivors who were previously prescribed the therapy for secondary prevention of cardiovascular and/or cerebrovascular disease.

According to investigators recurrent ICH affected 22 of 268 participants (8.2%) allocated to antiplatelet therapy. That’s compared to 25 of 268 participants (9.3%) allocated to avoid antiplatelet therapy (adjusted hazard ratio, 0.87; 95% CI, 0.49-1.55; P = .64) over the seven year follow up period.

Meanwhile a major vascular event affected 72 participants (26.8%) in the antiplatelet therapy group compared to 87 participants (32.5%) allocated to avoid antiplatelet therapy (hazard ratio, 0.79; 95% CI, 0.58-1.08; P = .14).

At least a third of ICH cases involve patients who will have been taking antiplatelet or anticoagulant therapy to prevent a heart attack or ischaemic stroke note investigators who say questions about the risk versus benefit of re-starting the therapy in this group of patients have largely gone unanswered.

They say the findings from RESTART should provide clinicians with ‘some reassurance’ about the use of antiplatelet therapy after ICH if indicated for secondary prevention of major vascular events.

Commenting on the trial, neurologist Professor Bruce Campbell, Head of Stroke at the Royal Melbourne Hospital and a Director and Chair of Clinical Council at the Stroke Foundation told the limbic the updated results address questions the original trial raised and suggest ‘a reasonable’ safety profile.

“The original trial found a trend towards reduced bleeding patients re-started on antithrombotics which was counterintuitive and unexpected. With the longer term follow-up now reported, this trend disappeared which makes more sense. Nonetheless the results still suggest a reasonable safety profile for restarting antithrombotics – something that was often considered ill-advised previously”.

As for when to re-initiate patients on antiplatelet therapy, Professor Campbell said that time is not yet known but offered the following advice:

“In RESTART the actual median time to restart was 76 days (75% >30 days and only 4% were re-started in the first week).  The expert opinion in the Australian Guidelines Practical Information is ‘in general, intracerebral haemorrhage expansion occurs in the first 24h and it is suggested to delay restarting antiplatelet medication for one week or more’.

But he remains cautious about reinstating antiplatelet thearpy particularly for one subgroup of patients.

“Any decision to restart antiplatelets after intracerebral haemorrhage requires careful individualised consideration of the risk and benefit. Patients with a lobar pattern of bleeding that often indicates amyloid angiopathy remain a group likely to have a higher risk of recurrent intracerebral haemorrhage. Although a difference in antiplatelet-related bleeding risk was not evident in this group in the RESTART trial, the risk and benefit remains more finely balanced in my opinion, based on the broader literature.”

The study is published in JAMA Neurology.

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