Effects of oral anticoagulation for atrial fibrillation after spontaneous intracranial haemorrhage in the UK: a randomised, open-label, assessor-masked, pilot-phase, non-inferiority trial,The Lancet Neurology

当前位置： X-MOL 学术 › Lancet Neurol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Effects of oral anticoagulation for atrial fibrillation after spontaneous intracranial haemorrhage in the UK: a randomised, open-label, assessor-masked, pilot-phase, non-inferiority trial
The Lancet Neurology ( IF 46.5 ) Pub Date : 2021-09-03 , DOI: 10.1016/s1474-4422(21)00264-7
Rustam Al-Shahi Salman , Catriona Keerie , Jacqueline Stephen , Steff Lewis , John Norrie , Martin S. Dennis , David E. Newby , Joanna M. Wardlaw , Gregory Y.H. Lip , Adrian Parry-Jones , Philip M. White , Colin Baigent , Dan Lasserson , Colin Oliver , Fiach O'Mahony , Shannon Amoils , John Bamford , Jane Armitage , Jonathan Emberson , Gabriël J.R. Rinkel , Gordon Lowe , Karen Innes , Kasia Adamczuk , Lynn Dinsmore , Jonathan Drever , Garry Milne , Allan Walker , Aidan Hutchison , Carol Williams , Ruth Fraser , Rosemary Anderson , Kate Covil , Kelly Stewart , Jessica Rees , Peter Hall , Alistair Bullen , Andrew Stoddart , Tom J. Moullaali , Jeb Palmer , Eleni Sakka , Joanne Perthen , Nicola Lyttle , Neshika Samarasekera , Allan MacRaild , Seona Burgess , Jessica Teasdale , Michelle Coakley , Pat Taylor , Gordon Blair , William Whiteley , Susan Shenkin , Una Clancy , Malcolm Macleod , Rachel Sutherland , Tom Moullaali , Amanda Barugh , Christine Lerpiniere , Fiona Moreton , Nicholas Fethers , Tal Anjum , Manju Krishnan , Peter Slade , Sharon Storton , Marie Williams , Caroline Davies , Lynda Connor , Glyn Gainard , Carl Murphy , Mark Barber , Derek Esson , James Choulerton , Louise Shaw , Suzanne Lucas , Sarah Hierons , Joanne Avis , Andrew Stone , Lukuman Gbadamoshi , Telma Costa , Lauren Pearce , Kirsty Harkness , Emma Richards , Jo Howe , Christine Kamara , Ralf Lindert , Ali Ali , Jahanzeb Rehan , Sarah Chapman , Maria Edwards , Raj Bathula , David Cohen , Joseph Devine , Mushiya Mpelembue , Priya Yesupatham , Swati Chhabra , Gbadebo Adewetan , Robert Ballantine , Daniel Brooks , Gemma Smith , Gill Rogers , Stuart Marsden , Sarah Clark , Ami Wilkinson , Ellen Brown , Lynsey Stephenson , Khin Nyo , Annie Abraham , Yogish Pai , Gek Shim , Vidya Baliga , Anand Nair , Matthew Robinson , Catherine Hawksworth , Jill Greig , Irfan Alam , Tonicha Nortcliffe , Ridha Ramiz , Ryan Shaw , Adrian Parry-Jones , Stephanie Lee , Tracy Marsden , Jane Perez , Emily Birleson , Rajendra Yadava , Mirriam Sangombe , Sam Stafford , Tom Hughes , Lucy Knibbs , Bethan Morse , Stefan Schwarz , Benjamin Jelley , Susan White , Bella Richard , Heidi Lawson , Sally Moseley , Michelle Tayler , Mandy Edwards , Claire Triscott , Rebecca Wallace , Angela Hall , Amanda Dell , Khalid Rashed , Sarah Board , Clare Buckley , Alfonso Tanate , Tressy Pitt-Kerby , Kate Beesley , Jess Perry , Christine Hellyer , Paul Guyler , Nisha Menon , Sharon Tysoe , Raji Prabakaran , Martin Cooper , Anoja Rajapakse , Inez Wynter , Susan Smith , Nic Weir , Cherish Boxall , Hannah Yates , Simon Smith , Pamela Crawford , James Marigold , Fiona Smith , Jake Harvey , Sue Evans , Laura Baldwin , Sarah Hammond , Paul Mudd , Angela Bowring , Samantha Keenan , Kevin Thorpe , Mohammad Haque , Joanne Taaffe , Natalie Temple , Tracey Peachey , Kim Wells , Fiona Haines , Nicola Butterworth-Cowin , Zoey Horne , Radim Licenik , Hayley Boughton , Timothy England , Amanda Hedstrom , Brian Menezes , Ruth Davies , Venetia Johnson , Simon Whittingham-Jones , David Werring , Sabaa Obarey , Caroline Watchurst , Amy Ashton , Shez Feerick , Nina Francia , Azra Banaras , Daniel Epstein , Marilena Marinescu , Annick Williams , Anna Robinson , Fiona Humphries , Ijaz Anwar , Arunkumar Annamalai , Susan Crawford , Vicky Collins , Lorna Shepherd , Elaine Siddle , Justin Penge , Daniel Epstein , Sam Qureshi , Vinodh Krishnamurthy , Vasileios Papavasileiou , Dean Waugh , Emelda Veraque , Nathan Douglas , Numan Khan , Sankaranarayanan Ramachandran , Peter Sommerville , Anthony Rudd , Sagal Kullane , Ajay Bhalla , Jonathan Birns , Rowshanara Ahmed , Meegan Gibbons , Eva Klamerus , Benjie Cendreda , Keith Muir , Nicola Day , Angela Welch , Wilma Smith , Jennifer Elliot , Salwa Eltawil , Ammad Mahmood , Kim Hatherley , Shirley Mitchell , Harjit Bains , Lauren Quinn , Rachel Teal , Ivie Gbinigie , George Harston , Phil Mathieson , Gary Ford , Ursula Schulz , James Kennedy , Kirubananthan Nagaratnam , Kiran Bangalore , Neelima Bhupathiraju , Chris Wharton , Ken Fotherby , Ahmad Nasar , Angie Stevens , Angela Willberry , Rachel Evans , Baljinder Rai , Chloe Blake , Kamy Thavanesan , Gail Hann , Tanith Changuion , Sara Nix , Amanda Whiting , Michelle Dharmasiri , Louise Mallon , Marketa Keltos , Nigel Smyth , Charlotte Eglinton , John Duffy , Ela Tone , Lucy Sykes , Emily Porter , Carolyn Fitton , Nikolaos Kirkineziadis , Gillian Cluckie , Kate Kennedy , Sarah Trippier , Rebecca Williams , Elizabeth Hayter , James Rackie , Bhavini Patel , Ghatala Rita , Adrian Blight , Val Jones , Liqun Zhang , Lillian Choy , Anthony Pereira , Brian Clarke , Samer Al-Hussayni , Lynn Dixon , Andrew Young , Adrian Bergin , David Broughton , Senthil Raghunathan , Benjamin Jackson , Jason Appleton , Gwendoline Wilkes , Amanda Buck , Carla Richardson , Judith Clarke , Lucy Fleming , Gemma Squires , Zhe Law , Camille Hutchinson , Vera Cvoro , Mandy Couser , Amanda McGregor , Sean McAuley , Susan Pound , Patricia Cochrane , Clare Holmes , Peter Murphy , Nicola Devitt , Mairead Osborn , Amy Steele , Lucy Belle Guthrie , Elizabeth Smith , Jonathan Hewitt , Natalie Chaston , Min Myint , Andrew Smith , Louise Fairlie , Michelle Davis , Beth Atkinson , Stephen Woodward , Valerie Hogg , Michelle Fawcett , Louise Finlay , Anand Dixit , Eleanor Cameron , Breffni Keegan , Jim Kelly , Dónal Concannon , Dipankar Dutta , Deborah Ward , Jon Glass , Susan O'Connell , Joseph Ngeh , Alison O'Kelly , Emma Williams , Suzanne Ragab , Damian Jenkinson , Judith Dube , Laura Gleave , Jacqui Leggett , Nisha Kissoon , Louise Southern , Utpal Naghotra , Maria Bokhari , Beverley McClelland , Katja Adie , Abhijit Mate , Frances Harrington , Ali James , Elizabeth Swanson , Terri Chant , Miriam Naccache , Abbie Coutts , Gillian Courtauld , Sarah Whurr , Sue Webber , Emily Shead , Robert Luder , Maneesh Bhargava , Elodie Murali , Larissa Cuenoud , Kath Pasco , O Speirs , Lianne Chapman , Linda Inskip , Lisa Kavanagh , Meena Srinivasan , Nichola Motherwell , Indranil Mukherjee , Louise Tonks , Denise Donaldson , Heather Button , Rebecca Wilcox , Fran Hurford , Rachel Logan , Andy Taylor , Tracie Arden , Michael Carpenter , Prabal Datta , Tajammal Zahoor , Linda Jackson , Ann Needle , Andrew Stanners , Imran Ghouri , Donna Exley , Salman Akhtar , Hollie Brooke , Shannen Beadle , Eoin O'Brien , Jobbin Francis , Joanne McGee , Elaine Amis , Jennifer Mitchell , Sarah Finlay , Devesh Sinha , Csilla Manoczki , Sam King , James Tarka , Sumita Choudhary , Jegamalini Premaruban , Dorothy Sutton , Pradeep Kumar , Charlotte Culmsee , Caroline Winckley , Holly Davies , Hilary Thatcher , Evangelos Vasileiadis , Basaam Aweid , Melinda Holden , Cathy Mason , Thant Hlaing , Gladys Madzamba , Tanya Ingram , Michelle Linforth , Claire Cullen , Nibu Thomas , John France , Afaq Saulat , Biju Bhaskaran , Pauline Fitzell , Kathleen Horan , Catherine Manyoni , Josie Garfield-Smith , Hannah Griffin , Stacey Atkins , Joan Redome , Girish Muddegowda , Holly Maguire , Adrian Barry , Nenette Abano , Resti Varquez , Joanne Hiden , Susan Lyjko , Alda Remegoso , Kay Finney , Adrian Butler , Martin Strecker , Mary Joan MaCleod , Janice Irvine , Sandra Nelson , German Guzmangutierrez , Jacqueline Furnace , Vicky Taylor , Hawraman Ramadan , Kim Storton , Sohail Hassan , Eman Abdus Sami , Ruth Bellfield , Kelvin Stewart , Outi Quinn , Chris Patterson , Hedley Emsley , Bindu Gregary , Shakeel Ahmed , Shakeelah Patel , Sonia Raj , Sulaiman Sultan , Fiona Wright , Peter Langhorne , Ruth Graham , Terry Quinn , Kate McArthur

Background

Oral anticoagulation reduces the rate of systemic embolism for patients with atrial fibrillation by two-thirds, but its benefits for patients with previous intracranial haemorrhage are uncertain. In the Start or STop Anticoagulants Randomised Trial (SoSTART), we aimed to establish whether starting is non-inferior to avoiding oral anticoagulation for survivors of intracranial haemorrhage who have atrial fibrillation.

Methods

SoSTART was a prospective, randomised, open-label, assessor-masked, parallel-group, pilot phase trial done at 67 hospitals in the UK. We recruited adults (aged ≥18 years) who had survived at least 24 h after symptomatic spontaneous intracranial haemorrhage, had atrial fibrillation, and had a CHA₂DS₂-VASc score of at least 2. Web-based computerised randomisation incorporating a minimisation algorithm allocated participants (1:1) to start or avoid long-term (≥1 year) full treatment dose open-label oral anticoagulation. The participants assigned to start oral anticoagulation received either a direct oral anticoagulant or vitamin K antagonist, and the group assigned to avoid oral anticoagulation received standard clinical practice (antiplatelet agent or no antithrombotic agent). The primary outcome was recurrent symptomatic spontaneous intracranial haemorrhage, and was adjudicated by an individual masked to treatment allocation. All outcomes were ascertained for at least 1 year after randomisation and assessed in the intention-to-treat population of all randomly assigned participants, using Cox proportional hazards regression adjusted for minimisation covariates. We planned a sample size of 190 participants (one-sided p=0·025, power 90%, allowing for non-adherence) based on a non-inferiority margin of 12% (or adjusted hazard ratio [HR] of 3·2). This trial is registered with ClinicalTrials.gov (NCT03153150) and is complete.

Findings

Between March 29, 2018, and Feb 27, 2020, consent was obtained at 61 sites for 218 participants, of whom 203 were randomly assigned at a median of 115 days (IQR 49–265) after intracranial haemorrhage onset. 101 were assigned to start and 102 to avoid oral anticoagulation. Participants were followed up for median of 1·2 years (IQR 0·97–1·95; completeness 97·2%). Starting oral anticoagulation was not non-inferior to avoiding oral anticoagulation: eight (8%) of 101 in the start group versus four (4%) of 102 in the avoid group had intracranial haemorrhage recurrences (adjusted HR 2·42 [95% CI 0·72–8·09]; p=0·152). Serious adverse events occurred in 17 (17%) participants in the start group and 15 (15%) in the avoid group. 22 (22%) patients in the start group and 11 (11%) patients in the avoid group died during the study.

Interpretation

Whether starting oral anticoagulation was non-inferior to avoiding it for people with atrial fibrillation after intracranial haemorrhage was inconclusive, although rates of recurrent intracranial haemorrhage were lower than expected. In view of weak evidence from analyses of three composite secondary outcomes, the possibility that oral anticoagulation might be superior for preventing symptomatic major vascular events should be investigated in adequately powered randomised trials.

Funding

British Heart Foundation, Medical Research Council, Chest Heart & Stroke Scotland.

中文翻译：

英国口服抗凝药对自发性颅内出血后心房颤动的影响：一项随机、开放标签、评估者不知情、试验阶段、非劣效性试验

背景

口服抗凝药可将心房颤动患者的全身栓塞率降低三分之二，但其对既往颅内出血患者的益处尚不确定。在开始或停止抗凝剂随机试验（SoSTART）中，我们的目的是确定对于患有房颤的颅内出血幸存者，开始服用抗凝剂是否不劣于避免口服抗凝剂。

方法

SoSTART 是一项在英国 67 家医院进行的前瞻性、随机、开放标签、评估者不参与、平行组、试点阶段试验。我们招募了在有症状的自发性颅内出血后存活至少 24 小时、患有心房颤动且 CHA ₂ DS ₂ -VASc 评分至少为 2 的成年人（年龄≥18 岁）。基于网络的计算机随机化结合了最小化算法分配参与者（1:1）开始或避免长期（≥1年）全治疗剂量开放标签口服抗凝药。被分配开始口服抗凝剂的参与者接受直接口服抗凝剂或维生素 K 拮抗剂，而被分配避免口服抗凝剂的组接受标准临床实践（抗血小板剂或不抗血栓剂）。主要结局是复发性症状性自发性颅内出血，并由不了解治疗分配的个体进行判定。所有结果均在随机分组后至少 1 年内确定，并使用针对最小化协变量调整的 Cox 比例风险回归在所有随机分配的参与者的意向治疗人群中进行评估。我们计划样本量为 190 名参与者（单边 p=0·025，功效 90%，允许非依从性），基于 12% 的非劣效性边际（或调整后的风险比 [HR] 为 3·2））。该试验已在 ClinicalTrials.gov (NCT03153150) 注册并已完成。

发现

2018年3月29日至2020年2月27日期间，在61个地点获得了218名参与者的同意，其中203名参与者在颅内出血发病后平均115天（IQR 49-265）被随机分配。 101 名患者被分配开始治疗，102 名患者被分配避免口服抗凝治疗。参与者的随访时间中位数为 1·2 年（IQR 0·97–1·95；完整性 97·2%）。开始口服抗凝治疗并不劣于避免口服抗凝治疗：开始组 101 人中有 8 人 (8%) 相对于避免组 102 人中有 4 人 (4%) 出现颅内出血复发（调整后 HR 2·42 [95% CI] 0·72–8·09]；p=0·152）。开始组有 17 名 (17%) 参与者发生严重不良事件，避免组有 15 名 (15%) 参与者发生严重不良事件。开始组中有 22 名患者 (22%) 和避免组有 11 名患者 (11%) 在研究期间死亡。