Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study
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Wilson, Duncan
Ambler, Gareth
Shakeshaft, Clare
Brown, Martin M
Charidimou, Andreas
Al-Shahi Salman, Rustam
Lip, Gregory Y H
Cohen, Hannah
Banerjee, Gargi
Houlden, Henry
White, Mark J
Yousry, Tarek A
Harkness, Kirsty
Flossmann, Enrico
Smyth, Nigel
Shaw, Louise J
Warburton, Elizabeth
Muir, Keith W
Jäger, Hans Rolf
Werring, David J
Aeron-Thomas, John
Aghoram, Prasanna
Amis, Elaine
Anderton, Peter
Andole, Sreeman
Anwar, Ijaz
Bamford, John
Banaras, Azra
Barry, Aian
Bellfied, Ruth
Benford, Aienne
Bhalla, Ajay
Bhargava, Maneesh
Bhaskaran, Biju
Bhupathiraju, Neelima
Birns, Jonathan
Blight, Aian
Bowring, Angie
Brown, Ellen
Bruce, David
Buck, Amanda
Bunworth, Kerry
Burger, Ilse
Burgess, Laura
Burn, Mathew
Burssens, Evelyn
Burton, Mauian
Butler, Nicola
Button, Denise
Carpenter, Michael
Chadha, Dinesh
Chatterjee, Kausik
Choy, Lillian
Cohen, David
Connell, Lynne
Cooper, Martin
Corrigan, John
Cotterill, Donna
Courtauld, Gillian
Crawford, Susan
Cullen, Claire
Dani, Krishna
Daniel, Amelia
Datta, Prabel
Davis, Michelle
Day, Nicola
Doherty, Mandy
Douglas, Catherine
Dunne, Karen
Edwards, Collette
Eglinton, Charlotte
Elmarimi, Abduelbaset
Emsley, Hedley
England, Timothy
Epstein, Daniel
Erande, Renuka
Esisi, Bernard
Evans, Rachel
Farren, Pamela
Fitzell, Pauline
Fletcher, Glyn
Gallifent, Rachel
Gascoyne, Rachel
Giallombardo, Elio
Gregary, Bindu
Gunathilagan, Gunaratam
Guyler, Paul
Hairsine, Brigid
Haley, Michael
Hardwick, Anne
Hargroves, David
Harrington, Frances
Hedstrom, Amanda
Holmes, Clare
Hussein, Senussi
Ingram, Tanya
Ispoglou, Sissi
Iveson, Liz
Johnson, Venetia
Justin, Frances
Kausar, Shahid
Kee, Karen
Keeling, Michael
Khan, Shagufta
Kieliszkowska, Agnieszka
Kingwell, Hayley
Krishnamurthy, Vinodh
Kullane, Sagal
Kumar, Balakrishna
Leach, Simon
Leason, Sana
Lopez, Paula
Luder, Robert
Madigan, Barbara
Maguire, Stuart
Maguire, Holly
Mahawish, Karim
Makawa, Linetty
Mamun, Maam
Manawadu, Dulka
Mangion, David
Manoj, Aravindakshan
Mansoor, Syed
Marsden, Tracy
Marsh, Rachel
Mashate, Sheila
McCormick, Michael
McGolick, Clare
McKee, Madeleine
Mckenzie, Emma
Meenakishundaram, Sanjeevikumar
Mellor, Zoe
Misra, Amulya
Mistri, Amit
Mohd Nor, Azlisham
Mpelembue, Mushiya
Murphy, Peter
Nallasivam, Arumug
Needle, Ann
Nguyen, Vinh
O'Connell, Janice
O'Mahony, Paul
Okwera, James
Orefo, Chukwuka
Owusu-Agyei, Peter
Parry, Anthea
Parry-Jones, Adrian
Pasco, Kath
Patterson, Chris
Peixoto, Cassilda
Perez, Jane
Persad, Nicola
Porteous, Mia
Power, Michael
Price, Christopher
Proschel, Harald
Punekar, Shuja
Putterill, Janet
Randall, Marc
Redjep, Ozlem
Rehman, Habib
Richards, Emma
Riddell, Victoria
Roffe, Christine
Rogers, Gill
Rudd, Anthony
Saastamoinen, Kari
Sajid, Mahmud
Sandhu, Banher
Schofield, Christine
Scott, Jon
Sekaran, Lakshmanan
Sharma, Pankaj
Sharma, Jagdish
Sharpe, Simon
Smith, Matthew
Smith, Anew
Sprigg, Nikola
Staals, Julie
Steele, Amy
Storey, Gail
Storey, Kelley
Subramonian, Santhosh
Sword, Jane
Tallon, Grainne
Tan, Garryck
Tate, Margaret
Teke, Jennifer
Temple, Natalie
Thompson, Teresa
Tysoe, Sharon
Vahidassr, Djamil
van der Kwaak, Anouk
Veltkamp, Roland
Walstow, Deborah
Watchurst, Caroline
Watson, Fran
Waugh, Dean
Wilkinson, Peter
Wilson, David
Wilson-Owen, Sarah
Wroath, Belinda
Wynter, Inez
Young, Emma
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1016/S1474-4422(18)30145-5Metadata
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Wilson, D., G. Ambler, C. Shakeshaft, M. M. Brown, A. Charidimou, R. Al-Shahi Salman, G. Y. H. Lip, et al. 2018. “Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study.” The Lancet. Neurology 17 (6): 539-547. doi:10.1016/S1474-4422(18)30145-5. http://dx.doi.org/10.1016/S1474-4422(18)30145-5.Abstract
Summary Background: Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Methods: Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Findings: Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively). Interpretation In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation. Funding The Stroke Association and the British Heart Foundation.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956310/pdf/Terms of Use
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