STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage: Protocol for a randomised controlled trial

Abstract

Background and aims Many patients with prior intracerebral haemorrhage have indications for antithrombotic treatment with antiplatelet or anticoagulant drugs for prevention of ischaemic events, but it is uncertain whether such treatment is beneficial after intracerebral haemorrhage. STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage will assess (i) the effects of long-term antithrombotic treatment on the risk of recurrent intracerebral haemorrhage and occlusive vascular events after intracerebral haemorrhage and (ii) whether imaging findings, like cerebral microbleeds, modify these effects. Methods STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage is a multicentre, randomised controlled, open trial of starting versus avoiding antithrombotic treatment after non-traumatic intracerebral haemorrhage, in patients with an indication for antithrombotic treatment. Participants with vascular disease as an indication for antiplatelet treatment are randomly allocated to antiplatelet treatment or no antithrombotic treatment. Participants with atrial fibrillation as an indication for anticoagulant treatment are randomly allocated to anticoagulant treatment or no anticoagulant treatment. Cerebral CT or MRI is performed before randomisation. Duration of follow-up is at least two years. The primary outcome is recurrent intracerebral haemorrhage. Secondary outcomes include occlusive vascular events and death. Assessment of clinical outcomes is performed blinded to treatment allocation. Target recruitment is 500 participants. Trial status: Recruitment to STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage is on-going. On 30 April 2020, 44 participants had been enrolled in 31 participating hospitals. An individual patient–data meta-analysis is planned with similar randomised trials.

Antithrombotic treatment after intracerebral hemorrhage: Surveys among stroke physicians in Scandinavia and the United Kingdom

“… 27 Several such randomized trials are ongoing. STATICH and RESTART‐France are currently investigating starting versus avoiding antiplatelet treatment after ICH, STATICH, 22 ENRICH‐AF, 34 ASPIRE, 35 PRESTIGE‐AF, 36 and A3ICH 37 are investigating starting versus avoiding anticoagulant treatment for atrial fibrillation after ICH. In addition, STROKECLOSE 38 is comparing left atrial appendage occlusion to the best medical treatment in ICH survivors with atrial fibrillation.…”

“…In the United Kingdom, we conducted two surveys, one in 2011 for antiplatelet treatment and one in 2015 for anticoagulant treatment. The three surveys were customized as preparation for randomized trials (STATICH in Scandinavia, RESTART and SoSTART in the United Kingdom), 13 , 15 , 22 which was the reason for the different approaches. The wording of the questions in the three surveys were different, but we were generally interested to measure the level of uncertainty among stroke physicians regarding this treatment dilemma.…”

Apixaban versus no anticoagulation after anticoagulation-associated intracerebral haemorrhage in patients with atrial fibrillation in the Netherlands (APACHE-AF): a randomised, open-label, phase 2 trial

“…In another small feasibility and safety trial (NASPAFICH, NCT02998905), patients with atrial fibrillation and intracerebral haemorrhage on or off anticoagulants were randomly allocated to a DOAC or aspirin; this study was stopped early after the inclusion of 30 patients. Five other studies are ongoing: ENRICH AF (NCT03950076), a study of edoxaban versus no anticoagulation in 1200 patients with intracranial haem orrhage and atrial fibrillation; ASPIRE (NCT03907046), which is assessing apixaban versus aspirin in 700 patients with intracerebral haemorrhage and atrial fibrillation; PRESTIGEAF (NCT03996772), assessing DOAC versus no antico agulation in 654 patients with intracerebral haemorrhage and atrial fibrillation; A3ICH (NCT03243175), assessing apixaban versus left atrial appendage occlusion versus no anticoagulation and no left atrial appendage occlusion in 300 patients with intracerebral haemorrhage and atrial fibrillation; and STATICH (NCT03186729), 29 assessing antithrombotic medication versus no antithrombotic medication in 500 patients with intracranial haemorrhage and an indication for antithrombotic drugs (including but not restricted to atrial fibrillation).…”

Risk of Cerebrovascular Events in Intracerebral Hemorrhage Survivors With Atrial Fibrillation: A Nationwide Cohort Study

“…Several randomized controlled trials are currently investigating the optimal antithrombotic treatment strategy for stroke prevention in ICH survivors with concomitant AF, 9–14 and 2 of these trials have now been concluded and reported. 22,23 Both trials were inconclusive and likely underpowered to detect a signal of benefit or harm from OAC treatment, and the trial investigators call for additional trial data to provide more robust evidence.…”

“…7,8 Several randomized controlled trials are currently investigating antithrombotic treatment options for stroke prevention in ICH survivors with concomitant AF. [9][10][11][12][13][14] An ongoing European multinational randomized controlled trial, the PRESTIGE-AF (Prevention of Stroke in Intracerebral Haemorrhage Survivors With Atrial Fibrillation) trial is investigating stroke prevention strategies in patients with AF surviving an ICH. 13 Patients are randomized to either a nonvitamin K antagonist oral anticoagulant (NOAC) or no anticoagulation.…”