Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

RESTART Collaboration

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. Funding: British Heart Foundation.

Original languageEnglish
Pages (from-to)2613-2623
Number of pages11
JournalThe Lancet
Volume393
Issue number10191
DOIs
Publication statusPublished - 29 Jun 2019

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Cerebral Hemorrhage
Stroke
Therapeutics
Blood Vessels
Vascular Diseases
Intracranial Hemorrhages
Random Allocation
Secondary Prevention
Anticoagulants

ASJC Scopus subject areas

  • Medicine(all)

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Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART) : a randomised, open-label trial. / RESTART Collaboration.

In: The Lancet, Vol. 393, No. 10191, 29.06.2019, p. 2613-2623.

Research output: Contribution to journalArticle

@article{5dd9f615f7a64f6ca74f6d83a2bb0feb,
title = "Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial",
abstract = "Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3{\%}). 12 (4{\%}) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9{\%}) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95{\%} CI 0·25–1·03]; p=0·060). 18 (7{\%}) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9{\%}) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15{\%}] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14{\%}] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. Funding: British Heart Foundation.",
author = "{RESTART Collaboration} and {Al-Shahi Salman}, Rustam and Dennis, {M. S.} and Sandercock, {P. A.G.} and Sudlow, {C. L.M.} and Wardlaw, {J. M.} and Whiteley, {W. N.} and Murray, {G. D.} and J. Stephen and Newby, {D. E.} and N. Sprigg and Werring, {D. J.} and White, {P. M.} and Colin Baigent and Daniel Lasserson and Frank Sullivan and Johanna Carrie and Javier Rojas and Shannon Amoils and John Bamford and Jane Armitage and Gabriel Rinkel and Gordon Lowe and Jonathan Emberson and Karen Innes and Lynn Dinsmore and Jonathan Drever and Carol Williams and David Perry and Connor McGill and David Buchanan and Allan Walker and Aidan Hutchison and Christopher Matthews and Ruth Fraser and Aileen McGrath and Ann Deary and Rosemary Anderson and Pauli Walker and Christian Hansen and Richard Parker and Aryelly Rodriguez and Macleod, {M. R.} and Thomas Gattringer and Jeb Palmer and Eleni Sakka and Jennifer Adil-Smith and David Minks and Dipayan Mitra and Priya Bhatnagar and Zhe Law",
year = "2019",
month = "6",
day = "29",
doi = "10.1016/S0140-6736(19)30840-2",
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TY - JOUR

T1 - Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART)

T2 - a randomised, open-label trial

AU - RESTART Collaboration

AU - Al-Shahi Salman, Rustam

AU - Dennis, M. S.

AU - Sandercock, P. A.G.

AU - Sudlow, C. L.M.

AU - Wardlaw, J. M.

AU - Whiteley, W. N.

AU - Murray, G. D.

AU - Stephen, J.

AU - Newby, D. E.

AU - Sprigg, N.

AU - Werring, D. J.

AU - White, P. M.

AU - Baigent, Colin

AU - Lasserson, Daniel

AU - Sullivan, Frank

AU - Carrie, Johanna

AU - Rojas, Javier

AU - Amoils, Shannon

AU - Bamford, John

AU - Armitage, Jane

AU - Rinkel, Gabriel

AU - Lowe, Gordon

AU - Emberson, Jonathan

AU - Innes, Karen

AU - Dinsmore, Lynn

AU - Drever, Jonathan

AU - Williams, Carol

AU - Perry, David

AU - McGill, Connor

AU - Buchanan, David

AU - Walker, Allan

AU - Hutchison, Aidan

AU - Matthews, Christopher

AU - Fraser, Ruth

AU - McGrath, Aileen

AU - Deary, Ann

AU - Anderson, Rosemary

AU - Walker, Pauli

AU - Hansen, Christian

AU - Parker, Richard

AU - Rodriguez, Aryelly

AU - Macleod, M. R.

AU - Gattringer, Thomas

AU - Palmer, Jeb

AU - Sakka, Eleni

AU - Adil-Smith, Jennifer

AU - Minks, David

AU - Mitra, Dipayan

AU - Bhatnagar, Priya

AU - Law, Zhe

PY - 2019/6/29

Y1 - 2019/6/29

N2 - Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. Funding: British Heart Foundation.

AB - Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. Funding: British Heart Foundation.

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