Effects of Antiplatelet Therapy After Stroke Caused by Intracerebral Hemorrhage
Authors: Rustam Al-Shahi Salman, Martin S. Dennis, Peter A. G. Sandercock, Cathie L. M. Sudlow, Joanna M. Wardlaw, William N. Whiteley, Gordon D. Murray, Jacqueline Stephen, Aryelly Rodriguez, Steff Lewis, David J. Werring, Phil M. White, Colin Baigent, Daniel Lasserson, Frank Sullivan, Johanna Carrie, David Newby, Nikola Sprigg, Javier Rojas, Bernadette Gallagher, Elizabeth Brownsell, Paul Dearie, Alice Graves, Louisa Wilson, Gelnna Hamer, Elizabeth Craig, Priscilla Sauramba, Nicola Lyttle, Shannon Amoils, John Bamford, Jane Armitage, Gabriel Rinkel, Gordon Lowe, Jonathan Emberson, Karen Innes, Lynn Dinsmore, Jonathan Drever, Carol Williams, David Perry, Connor McGill, David Buchanan, Allan Walker, Aidan Hutchison, Christopher Matthews, Ruth Fraser, Aileen McGrath, Ann Deary, Rosemary Anderson, Pauli Walker, Kasia Adamczuk, Christian Hansen, Richard Parker, Robert Lee, Malcolm Macleod, Thomas Moullaali, Jeb Palmer, Eleni Sakka, Jennifer Adil-Smith, David Minks, Dipayan Mitra, Priya Bhatnagar, Johannes du Plessis, Yogish Joshi, Kelly Stewart, Kate Covil, Mark Rodrigues, Christine Lerpiniere, Richard O’Brien, Seona Burgess, Gillian Mead, Ruth Paulton, Fergus Doubal, Katrina McCormick, Neil Hunter, Pat Taylor, Ruwan Parakramawansha, Jack Perry, Gordon Blair, Allan MacRaild, Adrian Parry-Jones, Mary Johnes, Stephanie Lee, Kelly Marie Shaw, Ilse Burger, Martin Punter, Andrea Ingham, Jane Perez, Zin Naing, Jordi Morell, Tracy Marsden, Andrea Hall, Sally Marshall, Louise Harrison, Rowilson Jarapa, Edith Wood, Victoria O’Loughlin, David Cohen, Silvie Davies, Kelechi Njoku, Mushiya Mpelembue, Laura Burgess, Radim Licenik, Mmua Ngwako, Nabeela Nisar, Rangah Niranchanan, Tatjana Roganova, Rajaram Bathula, Joseph Devine, Anette David, Anne Oshodi, Fenglin Guo, Emmanuelle Owoyele, Varthi Sukdeo, Robert Ballantine, Mudhar Abbdul-Saheb, Angela Chamberlain, Aberami Chandrakumar, Philip Poku, Kirsty Harkness, Emma Richards, Ali Ali, Catrin Blank, Faith Kibutu, Olesia Balitska, Kathryn Birchall, Pauline Bayliss, Kathy Stocks, Arshad Majis, Clare Doyle, Jo Howe, Christine Kamara, Luke Barron, Ahmad Maatouk, Ralf Lindert, Katy Dakin, Jessica Redgrave, John France, Dawn Tomlin, Helen Bearne, Isam Salih, Debs Kelly, Susan Szabo, Biju Bhaskaran, Jean Buxton, Pauline Fitzell, Georgina Ayres, Afaq Saulat, Kathleen Horan, Joanne Garfield-Smith, Harbens Bhakri, Stacey Atkins, Joan Redome, Paul Guyler, Thayalini Loganathan, Amber Siddiqui, Anwer Siddiqui, Lucy Coward, Devesh Sinha, Swapna Kunhunny, Sharon Tysoe, Rajalakshmi Orath Prabakaran, Shyam Kelavkar, Sindhu Rashmi, David Ngo, Kheng Xiong Ng, Nisha Menon, Sweni Shah, Mark Barber, Derek Esson, Fiona Brodie, Talat Anjum, Manju Krishnan, Leanne Quinn, Jayne Spencer, Terry Jones, Helen Thompson Jones, Srikanth Chenna, Sharon Storton, Lynne Dacey, Sarah Thomas, Teresa Beaty, Mushtaq Wani, Shelley Treadwell, Caroline Davies, Susan Tucker, Lynda Connor, Glyn Gainard, Peter Slade, Girish Muddegowda, Nenette Abano, Alda Remegoso, Racquel Carpio, Chelsea Causley, Stephanie Stevens, Adrian Butler, Resti Varquez, Andrew Moores, Francis Alipio, Hayley Denic, Ranjan Sanyal, Adrian Barry, Holly Maguire, Jeanette Grocott, Kay Finney, Sue Lyjko, Christine Roffe, Joanne Hiden, Phillip Ferdinand, Vera Cvoro, Khalil Ullah, Nicola Chapman, Mandy Couser, Susan Pound, Sean Mcauley, Senthil Raghunathan, Faye Shelton, Amanda Hedstrom, Margi Godfrey, Diane Havard, Amanda Buck, Kailash Krishnan, Nicola Gilzeane, Jack Roffe, Judith Clarke, Saima Sheikh, Katherine Whittamore, Rekha Keshvara, Carla Jordan, Gwendoline Wilkes, Benjamin Jackson, Jason Appleton, Zhe Law, Oliver Matias, Evangelos Vasileiadis, Cathy Mason, Anthea Parry, Geraldine Landers, Melinda Holden, Basaam Aweid, Khalid Rashed, Linda Balian, Carinna Vickers, Elizabeth Keeling, Sarah Board, Joanna Allison, Clare Buckley, Barbara Williams-Yesson, Joanne Board, Tressy Pitt-Kerby, Alfonso Tanate, Diane Wood, Dinesh Chadha, Manohar Kini, Deborah Walstow, Rosanna Fong, Robert Luder, Tolu Adesina, Jill Gallagher, Hayley Bridger, Elodie Murali, Larissa Cuenoud, Maneesh Bhargava, Chloe Van Someren, Katja Adie, Gillian Courtauld, Christine Schofield, Abhijit Mate, Ali James, Frances Harrington, Linda Lucas, Kirsty Bond, Bev Maund, Sam Ellis, Emilie Williams, Sue Webber, Terri Chant, Elizabeth Swanson, Eleanor King, Abbie Coutts, Nicola Yeo, Paul Mudd, Martin James, Hayley Kingwell, Caroline Roughan, Anthony Hemsley, Jane Sword, Samantha Keenan, Angela Bowring, Julie Cageao, David Strain, Keniesha Miller, Anita Goff, Karin Gupwell, Kevin Thorpe, Hedley Emsley, Alison McLoughlin, Sulaiman Sultan, Shuja Punekar, Bindu Gregory, Sonia Raj, Donna Doyle, Keith Muir, Wilma Smith, Fiona Moreton, Bharath Kumar Cheripelli, Salwa El Tawil, Dheeraj Kalladka, Angela Welch, Xuya Huang, Nicola Day, Sankaranarayanan Ramachandran, Caroline Crosbie, Jennifer Elliot, Peter Sommerville, Meegan Gibbons, Rowshanara Ahmed, Sagal Kullane, Katherine Marks, Ajay Bhalla, Jonathan Birns, Tony Rudd, Nic Weir, Christopher Allen, Vanessa Pressly, Pam Crawford, Emma Battersby-Wood, Alex Blades, Shuna Egerton, Ashleigh Walters, James Richard Marigold, Sue Evans, Fiona Smith, Gabriella Howard, Imogen Gartrell, Simon Smith, Chloe Cox, Robyn Creeden, Cherish Boxall, Jonathan Hewitt, Claire Nott, Procter Sarah, Jessica Whiteman, Steve Buckle, Rina Mardania, Jane Gray, Rebecca Wallace, Claire Triscott, Anand Nair, Jill Greig, Pratap Rana, Matthew Robinson, Mohammad Irfan Alam, Ridha Ramiz, David Werring, Duncan Wilson, Caroline Watchurst, Maria Brezitski, Ifan Jones, Luci Crook, Azra Banaras, Krishna Patel, Renuka Erande, Caroline Hogan, Talal Al-Mayhani, Isabel Hostettler, Amy Ashton, Shez Feerick, Nina Francia, Nnebuife Oji, Emma Elliott, Martin Dennis, William Whiteley, Cathie Sudlow, Dipankar Dutta, Pauline Brown, Deborah Ward, Fiona Davis, Jennifer Turfrey, Chloe Hughes, Kayleigh Collins, Rehana Bakawala, Susan O'Connell, Jon Glass, David Broughton, Lynn Dixon, Kath Chapman, Andrew Young, Adrian Bergin, Dinesh Tryambake, Andrew Sigsworth, Aravind Manoj, Paula Lopez, Penelope Cox, Glyn Fletcher, Mark Wilkinson, Paul Fitzsimmons, Nikhil Sharma, James Choulerton, Denise Button, Lindsey Dow, Lukuman Gbadamoshi, Joanne Avis, Barbara Madigan, Mccann Stephanie, Louise Shaw, Deborah Howcroft, Suzanne Lucas, Andrew Stone, Gillian Cluckie, Brian Clarke, Natasha Clarke, Neha Chopra, Bhavini Patel, Kate Kennedy, Rebecca Williams, Adrian Blight, Joanna Oreilly, Chukwuka Orefo, Nilofer Dayal, Rita Ghatala, Temi Adedoyin, Caroline Lovelock, Fran Watson, Sarah Trippier, Lillian Choy, Barry Moynihan, Usman Khan, Val Jones, Naomi Jeyaraj, Lourda Kerin, Kamy Thavanesan, Chantel Cox, Arshi Iqbal, Caroline Bagnall, Anja Ljubez, Marketa Keltos, Josh Roberts, Becky Jupp, Laura Tucker, Tanith Changuion, Catherine Ovington, Emily Rogers, Owen David, Jo Bell, Barbara Longland, Gail Hann, Divya Tiwari, Martin Cooper, Mohammad Nasar, Anoja Rajapakse, Inez Wynter, Ijaz Anwar, Helen Skinner, Tarn Nozedar, Damian Mcardle, Balakrishna Kumar, Susan Crawford, Arunkumar Annamalai, Alex Ramshaw, Clare Holmes, Mairead Osborn, Emily Dodd, Peter Murphy, Nicola Devitt, Pauline Baker, Amy Steele, Lucy Belle Guthrie, Sarah Caine, Samantha Clarke, Ahamad Hassan, Dean Waugh, Emelda Veraque, Linetty Makawa, Mary Kambafwile, Marc Randall, Vasileios Papavasileiou, Claire Cullen, Jenny Peters, Hlaing Thant, Tanya Ingram, Mellor Zoe, Ramesh Durairaj, Melanie Harrison, Daniela Shackcloth, Jordan Ewing, Sarah Stevenson, Victoria Sutton, Mark McCarron, Jacqueline McKee, Mandy Doherty, Ferghal McVerry, Caroline Blair, Donal Concannon, Mary Macleod, Janice Irvine, Heather Gow, Jacqueline Furnace, Anu Joyson, Baljit Jagpal, Sarah Ross, Katrina Klaasen, Beverly Maclennan, Sandra Nelson, Rebecca Clarke, Nichola Crouch, Vicky Taylor, Daniel Epstein, Avani Shukla, Vinodh Krishnamurthy, Paul Nicholas, Sammie Qureshi, Adam Webber, Justin Penge, Hawraman Ramadan, Stuart Maguire, Chris Patterson, Ruth Bellfield, Brigid Hairsine, Kelvin Stewart, Michaela Hooley, Outi Quinn, Bella Richard, Sally Moseley, Mandy Edwards, Heidi Lawson, Michelle Tayler, Yogish Pai, Gemma Marie Smith, Mark Garside, Mahesh Dhakal, Muhammad Naeem, Vidya Baliga, Gill Rogers, Ellen Brown, David Bruce, Susan Clayton, Rachel Hayman, Sofia Dima, Ed Gamble, Rebecca Grue, Bethan Charles, Adam Hague, Sujata Blane, Caroline Lambert, Afnan Chaudhry, Thomas Harrison, Laura Howaniec, Dionne Hove, Gemma Grimwood, Kari Saastamoinen, Ozlem Redjep, Fiona Humphries, Lucia Argandona, Esther Erumere, Sageet Amlani, Grace Auld, Afraim Salek-Haddadi, Ursula Schulz, Philip Mathieson, Ian Reckless, James Kennedy, Gary Ford, Rachel Teal, Giulia Lenti, George Harston, Eoin Obrien, Sarah Finlay, Helen Hayhoe, Sarah Crisp, Juliana Sesay, George Zachariah, Jobbin Francis, Dominic Handley, Siobhan Kelly, Joanne Mcgee, Jennifer Mitchell, Elaine Amis, Niamh Hannon, Tom Hughes, Bethan Morse, Henry De Berker, Susan White, Emma Tallantyre, Ahmed Osman, Lucy Knibbs, Stefan Schwarz, Benjamin Jelley, Rajendra Yadava, Julie Reddan, Mirriam Sangombe, Khalid Azhar, Samantha Stafford, Nasar Ahmad, Ken Fotherby, Debbie Morgan, Farrukh Baig, Karla Jennings-Preece, Donna Butler, Baljinder Rai, Angela Willberry, Angela Stevens, Prasad Siddegowda, Lisa Hyatt, Peter Howard, David Jarrett, Suheil Ponnambath, Tracey Dobson, Jane Tandy, Claire James, Stacey Valentine, Yasmin Harrington-Davies, Rebecca Butler, Anne Suttling, Fiona Wright, Gillian Kerr, Ruth Graham, Christine McAlpine, Peter Langhorne, Mohammad Shahzad Iqbal, Louise Humphreys, Kath Pasco, Olga Balazikova, Ashraf Nasim, Cassilda Peixoto, Louise Gallagher, Shahrzad Shahmehri, Sandip Ghosh, Elizabeth Barrie, Danielle Gilmour, Margo Henry, Tom Webb, Linda Cowie, Hannah Rudenko, Natasha Schumacher, Shanni Mcdonald, Susannah Walker, Tracey Cosier, Anna Verrion, Eva Beranova, Audrey Thomson, Marius Venter, Sheila Mashate, Kirsten Harvey, Léjeune Gardener, Vinh Nguyen, Omid Halse, Olivia Geraghty, Beth Hazel, Peter Wilding, Victoria Tilley, Arindam Kar, Louise Southern, Tim Cassidy, Bernard Esisi, Beverley McClelland, Maria Bokhari, Timothy England, Mohana Maddula, Richard Donnelly, Paul Findlay, Ian Shread, Ashish Macaden, Charlotte Barr, Azlisham Mohd Nor, Nicola Persad, Charlotte Eglinton, Marie Weinling, Claire Brown, Benjamin Hyams, Alex Shah, John Baker, Anthony Byrne, Caroline Mcghee, Amanda Smart, Claire Copeland, Michael Carpenter, Marion Walker, Richard Davey, Ann Needle, Razik Fathima, Gavin Bateman, Andrew Stanners, Prabal Datta, Linda Jackson, Julie Ball, Michelle Davis, Natalie Atkinson, Michelle Fawcett, Teresa Thompson, Helen Guy, Valerie Hogg, Carole Hays, Stephen Woodward, Mohammad Haque, Stuart Symonds, Mehran Maanoosi, Jane Herman, Toby Black, Caroline Clarke, Skelton Miriam, Alpha Anthony, Michele Tribbeck, Julie Cronin, Denise Mead, Ruth Fennelly, James McIlmoyle, Christina Dickinson, Carol Jeffs, Joanne Howard, Sajjad Anwar, Kirsty Jones, Saikat Dhar, Muhammad Siddiq, Caroline Clay, Simone Ivatts, Yolanda Baird, Moore Sally, Lisa Clayton- Evans, Sophie Newton, Isobel Amey, Indra Chadbourn, Rayessa Rayessa, Lisa Wilson, Alicia Rodgers, Charde Naylor, Sarah Wilson, Emma Clarkson, Ruth Davies, Paula Owings, Graeme Sangster, Valerie Gott, Victoria Little, Pauline Weir, Suja Cherian, Deepa Jose, Helen Moroney, Susan Downham, Angela Dodd, Venetia Vettimootal Johnson, Laura Codd, Naomi Robinson, Ashraf Ahmed, Sharon Johnson, Carol Denniss, Mo Albazzaz, Mishell Cunningham, Tajammal Zahoor, Timothy Webster, Sandra Leason, Syed Haider, Kausic Chatterjee, Arumugam Nallasivan, Charlotte Perkins, Samantha Seagrave, Colin Jenkins, Fiona Price, Claire Hughes, Lily Mercer, Malik Hussain, Sarah Brown, Miriam Harvey, Robert Whiting, Mohammad Khan, Jane Homan, Leanne Foote, Nicholas Hunt, Helen Durman, Lucy Brotherton, Jayne Foot, Corinne Pawley, Eliza Foster, Alison Whitcher, Kneale Metcalf, Jenny Jagger, Susan McDonald, Kelly Waterfield, Patrick Sutton, Naval Shinh, Ajmal Anversha, Garth Ravenhill, Richard Greenwood, Janak Saada, Alison Wiltshire, Rebekah Perfitt, Magdalini Krommyda, Evelyne Burssens, Naveen Gadapa, Karen Dunne, Sreeman Andole, Sam King, Catherine Plewa, Nigel Smyth, Jenny Wilson, Elio Giallombardo, Lucy Sykes, Pradeep Kumar, James Barker, Linda Dunn, Isabel Huggett, Charlotte Culmsee, Philip Thomas, Min Myint, Helen Brew, Nikhil Majmudar, Janice Oconnell, George Bunea, Charlotte Fox, Diane Gulliver, Andrew Smith, Betty Mokoena, Naweed Sattar, Ramesh Krishnamurthy, Emily Osborne, David Wilson, Belinda Wroath, Kevin Dynan, Michael Power, Susan Thompson, Victoria Adell, Enoch Orugun, Una Poultney, Rachel Glover, Hannah Crowther, Sarah Thornthwaite, Ivan Wiggam, Aine Wallace, Enda Kerr, Ailsa Fulton, Annemarie Hunter, Suzanne Tauro, Sarah Cuddy, David Mangion, Skarlet Markova, Anne Hardwick, Tara Lawrence, Carmen Constantin, Jo Fletecher, Isobel Thomas, Kerry Pettitt, Lakshmanan Sekaran, Frances Justin, Margaret Tate, Kiranjit Bharaj, Rohan Simon, Niaz Mohammed, Sakthivel Sethuraman, Duke Phiri, Meena Chauhan, Khaled Elfandi, Uzma Khan, David Eveson, Amit Mistri, Lisa Manning, Shagufta Khan, Champa Patel, Mohammed Moqsith, Saira Sattar, Man Yee Lam, Kashif Musarrat, Claire Stephens, Latheef Kalathil, Richard Miller, Maqsud Salehin, Nikki Gautam, Duncan Bailey, Amor Kelly, Julie Meir, Javed Imam, Lisa Wood, Anne Nicolson, Julie White, Mahmud Sajid, George Ghaly, Margaret Ball, Rachel Gascoyne, Harald Proeschel, Simon Sharpe, Sarah Horton, Emily Beaves, Stephanie Jones, Brigitte Yip, Murdina Bell, Linda MacLiver, Brian MacInnes, Don Sims, Jennifer Hurley, Mark Willmot, Claire Sutton, Edward Littleton, Susan Maiden, Rachael Jones, James Cunningham, Carole Green, Michelle Bates, Raj Shekhar, Ellie Gilham, Iman Ahmed, Rachel Crown, Tracy Fuller, Neetish Goorah, Angela Bell, Christine Kelly, Arun Singh, Jamie Walford, Benjamin Tomlinson, Farzana Patel, Stephen Duberley, Ingrid Kane, Nicola Gainsborough, Chakravarthi Rajkumar, Jane Gaylard, Joanna Breeds, Alexandra Pitt-Ford, Emma Barbon, Laura Latter, Philip Thompson, Simon Hervey, Joseph Vassallo, Shrivakumar Krishnamoorthy, Deborah Walter, Helen Cochrane, Meena Srinivasan, Robert Campbell, Denise Donaldson, Nichola Motherwell, Frances Hurford, Indranil Mukherjee, Antony Kenton, Sheila Nyabadza, Irene Martin, Benjamin Hunt, Hardi Hassan, Bander Dallol, Sarah O'toole, Janet Putterill, Ratneshwari Jha, Rachel Gallifent, Puneet Kakar, Aparna Pusalkar, Kelly Chan, Puneet Dangri, Hannah Beadle, Angela Cook, Karen Crabtree, Santhosh Subramonian, Natalie Temple, Peter Owusu-Agyei, Nicola Butterworth-Cowin, Suzanne Ragab, Kerstin Knops, Emma Jinks, Judith Dube, Christine Dickson, Laura Gleave, Jacqui Leggett, Tatiana Garcia, Sissy Ispoglou, Rachel Evans, Sandeep Ankolekar, Anne Hayes, Hlaing Ni, Josette Milligan, Bithi Rahman, Carol Graham, Josin Jose, Breffni Keegan, Jim Kelly, James White, Kelly Thomas, Lisa Mellish, Richard Dewar
Journal: JAMA Neurology (2021)

<h3>Importance</h3> The Restart or Stop Antithrombotics Randomized Trial (RESTART) found that antiplatelet therapy appeared to be safe up to 5 years after intracerebral hemorrhage (ICH) that had occurred during antithrombotic (antiplatelet or anticoagulant) therapy. <h3>Objectives</h3> To monitor adherence, increase duration of follow-up, and improve precision of estimates of the effects of antiplatelet therapy on recurrent ICH and major vascular events. <h3>Design, Setting and Participants</h3> From May 22, 2013, through May 31, 2018, this prospective, open, blinded end point, parallel-group randomized clinical trial studied 537 participants at 122 hospitals in the UK. Participants were individuals 18 years or older who had taken antithrombotic therapy for the prevention of occlusive vascular disease when they developed ICH, discontinued antithrombotic therapy, and survived for 24 hours. After initial follow-up ended on November 30, 2018, annual follow-up was extended until November 30, 2020, for a median of 3.0 years (interquartile range [IQR], 2.0-5.0 years) for the trial cohort. <h3>Interventions</h3> Computerized randomization that incorporated minimization allocated participants (1:1) to start or avoid antiplatelet therapy. <h3>Main Outcomes and Measures</h3> Participants were followed up for the primary outcome (recurrent symptomatic ICH) and secondary outcomes (all major vascular events) for up to 7 years. Data from all randomized participants were analyzed using Cox proportional hazards regression, adjusted for minimization covariates. <h3>Results</h3> A total of 537 patients (median age, 76.0 years; IQR, 69.0-82.0 years; 360 [67.0%] male; median time after ICH onset, 76.0 days; IQR, 29.0-146.0 days) were randomly allocated to start (n = 268) or avoid (n = 269 [1 withdrew]) antiplatelet therapy. The primary outcome of recurrent ICH affected 22 of 268 participants (8.2%) allocated to antiplatelet therapy compared with 25 of 268 participants (9.3%) allocated to avoid antiplatelet therapy (adjusted hazard ratio, 0.87; 95% CI, 0.49-1.55;<i>P</i> = .64). A major vascular event affected 72 participants (26.8%) allocated to antiplatelet therapy compared with 87 participants (32.5%) allocated to avoid antiplatelet therapy (hazard ratio, 0.79; 95% CI, 0.58-1.08;<i>P</i> = .14). <h3>Conclusions and Relevance</h3> Among patients with ICH who had previously taken antithrombotic therapy, this study found no statistically significant effect of antiplatelet therapy on recurrent ICH or all major vascular events. These findings provide physicians with some reassurance about the use of antiplatelet therapy after ICH if indicated for secondary prevention of major vascular events. <h3>Trial Registration</h3> isrctn.org Identifier:ISRCTN71907627