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

Al-Shahi Salman, R. et al. (2019) 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. Lancet Neurology, 18(7), pp. 643-652. (doi: 10.1016/S1474-4422(19)30184-X) (PMID:31129065)

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Abstract

Background: Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy. Methods: RESTART was a prospective, randomised, open-label, blinded-endpoint, parallel-group trial at 122 hospitals in the UK that assessed whether starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. For this prespecified subgroup analysis, consultant neuroradiologists masked to treatment allocation reviewed brain CT or MRI scans performed before randomisation to confirm participant eligibility and rate features of the intracerebral haemorrhage and surrounding brain. We followed participants for primary (recurrent symptomatic intracerebral haemorrhage) and secondary (ischaemic stroke) outcomes for up to 5 years (reported elsewhere). For this report, we analysed eligible participants with intracerebral haemorrhage according to their treatment allocation in primary subgroup analyses of cerebral microbleeds on MRI and in exploratory subgroup analyses of other features on CT or MRI. The trial is registered with the ISRCTN registry, number ISRCTN71907627. Findings: Between May 22, 2013, and May 31, 2018, 537 participants were enrolled, of whom 525 (98%) had intracerebral haemorrhage: 507 (97%) were diagnosed on CT (252 assigned to start antiplatelet therapy and 255 assigned to avoid antiplatelet therapy, of whom one withdrew and was not analysed) and 254 (48%) underwent the required brain MRI protocol (122 in the start antiplatelet therapy group and 132 in the avoid antiplatelet therapy group). There were no clinically or statistically significant hazards of antiplatelet therapy on recurrent intracerebral haemorrhage in primary subgroup analyses of cerebral microbleed presence (2 or more) versus absence (0 or 1) (adjusted hazard ratio [HR] 0·30 [95% CI 0·08–1·13] vs 0·77 [0·13–4·61]; pinteraction=0·41), cerebral microbleed number 0–1 versus 2–4 versus 5 or more (HR 0·77 [0·13–4·62] vs 0·32 [0·03–3·66] vs 0·33 [0·07–1·60]; pinteraction=0·75), or cerebral microbleed strictly lobar versus other location (HR 0·52 [0·004–6·79] vs 0·37 [0·09–1·28]; pinteraction=0·85). There was no evidence of heterogeneity in the effects of antiplatelet therapy in any exploratory subgroup analyses (all pinteraction>0·05). Interpretation: Our findings exclude all but a very modest harmful effect of antiplatelet therapy on recurrent intracerebral haemorrhage in the presence of cerebral microbleeds. Further randomised trials are needed to replicate these findings and investigate them with greater precision.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Huang, Dr Xuya and Langhorne, Professor Peter and Elliot, Dr Jennifer and Kerr, Dr Gillian and Moreton, Dr Fiona and Ramachandran, Dr Sankaranarayana and Cheripelli, Dr Bharath Kumar and El Tawil, Dr Salwa and Muir, Professor Keith and Smith, Mrs Wilma and Kalladka, Dr Dheeraj and McAlpine, Dr Christine
Authors: Al-Shahi Salman, R., Minks, D. P., Mitra, D., Rodrigues, M. A., Bhatnagar, P., du Plessis, J. C., Joshi, Y., Dennis, M. S., Murray, G. D., Newby, D. E., Sandercock, P. A. G., Sprigg, N., Stephen, J., Sudlow, C. L. M., Werring, D. J., Whiteley, W. N., Wardlaw, J. M., White, P. M., Baigent, C., Lasserson, D., Sullivan, F., Carrie, J., Rojas, J., Amoils, S., Bamford, J., Armitage, J., Rinkel, G., Lowe, G., Emberson, J., Innes, K., Dinsmore, L., Drever, J., Williams, C., Perry, D., McGill, C., Buchanan, D., Walker, A., Hutchison, A., Matthews, C., Fraser, R., McGrath, A., Deary, A., Anderson, R., Walker, P., Hansen, C., Parker, R., Rodriguez, A., Macleod, M., Gattringer, T., Palmer, J., Sakka, E., Adil-Smith, J., Minks, D., Mitra, D., Bhatnagar, P., du Plessis, J., Joshi, Y., Lerpiniere, C., O'Brien, R., Burgess, S., Mead, G., Paulton, R., Doubal, F., McCormick, K., Hunter, N., Taylor, P., Parakramawansha, R., Perry, J., Blair, G., MacRaild, A., Parry-Jones, A., Johnes, M., Lee, S., Shaw, K. M., Burger, I., Punter, M., Ingham, A., Perez, J., Naing, Z., Morell, J., Marsden, T., Hall, A., Marshall, S., Harrison, L., Jarapa, R., Wood, E., O'Loughlin, V., Cohen, D., Davies, S., Njoku, K., Mpelembue, M., Burgess, L., Licenik, R., Ngwako, M., Nisar, N., Niranchanan, R., Roganova, T., Bathula, R., Devine, J., David, A., Oshodi, A., Guo, F., Owoyele, E., Sukdeo, V., Ballantine, R., Abbdul-saheb, M., Chamberlain, A., Chandrakumar, A., Poku, P., Harkness, K., Blank, C., Richards, E., Ali, A., Kibutu, F., Balitska, O., Birchall, K., Bayliss, P., Doyle, C., Stocks, K., Majis, A., Howe, J., Kamara, C., Barron, L., Maatouk, A., Lindert, R., Dakin, K., Redgrave, J., Bhaskaran, B., Salih, I., Kelly, D., Szabo, S., Tomlin, D., Bearne, H., Buxton, J., Fitzell, P., Ayres, G., Saulat, A., Horan, K., Garfield-Smith, J., Bhakri, H., Guyler, P., Sinha, D., Loganathan, T., Siddiqui, A., Siddiqui, A., Coward, L., Kunhunny, S., Tysoe, S., Orath Prabakaran, R., Kelavkar, S., Rashmi, S., Ngo, D., Ng, K. X., Menon, N., Shah, S., Barber, M., Esson, D., Brodie, F., Anjum, T., Wani, M., Krishnan, M., Quinn, L., Spencer, J., Jones, T., Thompson-Jones, H., Dacey, L., Chenna, S., Storton, S., Thomas, S., Beaty, T., Treadwell, S., Davies, C., Tucker, S., Connor, L., Slade, P., Gainard, G., Muddegowda, G., Sanyal, R., Remegoso, A., Abano, N., Causley, C., Carpio, R., Stevens, S., Butler, A., Varquez, R., Denic, H., Alipio, F., Moores, A., Barry, A., Maguire, H., Grocott, J., Finney, K., Lyjko, S., Roffe, C., Hiden, J., Ferdinand, P., Cvoro, V., Ullah, K., Chapman, N., Couser, M., Pound, S., McCormick, K., Mcauley, S., Raghunathan, S., Shelton, F., Hedstrom, A., Godfrey, M., Havard, D., Buck, A., Krishnan, K., Gilzeane, N., Roffe, J., Clarke, J., Whittamore, K., Sheikh, S., Sprigg, N., Keshvara, R., Jordan, C., Jackson, B., Wilkes, G., Appleton, J., Law, Z., Matias, O., Vasileiadis, E., Mason, C., Parry, A., Landers, G., Holden, M., Aweid, B., Rashed, K., Balian, L., Vickers, C., Keeling, E., Board, S., Allison, J., Buckley, C., Williams-Yesson, B., Board, J., Pitt-Kerby, T., Tanate, A., Wood, D., Kini, M., Chadha, D., Walstow, D., Fong, R., Luder, R., Adesina, T., Gallagher, J., Bridger, H., Murali, E., Bhargava, M., van Someren, C., Harrington, F., Mate, A., James, A., Courtauld, G., Schofield, C., Adie, K., Lucas, L., Bond, K., Maund, B., Ellis, S., Mudd, P., James, M., Keenan, S., Bowring, A., Cageao, J., Kingwell, H., Roughan, C., Hemsley, A., Sword, J., Strain, D., Miller, K., Goff, A., Gupwell, K., Thorpe, K., Emsley, H., Punekar, S., McLoughlin, A., Sultan, S., Gregory, B., Raj, S., Doyle, D., Muir, K., Smith, W., Welch, A., Moreton, F., Cheripelli, B. 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College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Lancet Neurology
Publisher:Elsevier
ISSN:1474-4422
ISSN (Online):1474-4465
Published Online:22 May 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Lancet Neurology 18(7):643-652
Publisher Policy:Reproduced under a Creative Commons license

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