TY - JOUR
T1 - Early versus Late initiation of direct oral Anticoagulants in post-ischaemic stroke patients with atrial fibrillatioN (ELAN)
T2 - Protocol for an international, multicentre, randomised-controlled, two-arm, open, assessor-blinded trial
AU - Fischer, Urs
AU - Trelle, Sven
AU - Branca, Mattia
AU - Salanti, Georgia
AU - Paciaroni, Maurizio
AU - Ferrari, Cecilia
AU - Abend, Stefanie
AU - Beyeler, Seraina
AU - Strbian, Daniel
AU - Thomalla, Götz
AU - Ntaios, George
AU - Bonati, Leo H.
AU - Michel, Patrik
AU - Nedeltchev, Krassen
AU - Gattringer, Thomas
AU - Sandset, Else Charlotte
AU - Kelly, Peter
AU - Lemmens, Robin
AU - Koga, Masatoshi
AU - Sylaja, Padmavathy N.
AU - de Sousa, Diana Aguiar
AU - Bornstein, Natan M.
AU - Gdovinova, Zuzana
AU - Seiffge, David J.
AU - Gralla, Jan
AU - Horvath, Thomas
AU - Dawson, Jesse
N1 - Publisher Copyright:
© European Stroke Organisation 2022.
PY - 2022/12
Y1 - 2022/12
N2 - Rationale: Direct oral anticoagulants (DOAC) are highly effective in preventing ischaemic strokes in people with atrial fibrillation (AF). However, it is unclear how soon they should be started after acute ischaemic stroke (AIS). Early initiation may reduce early risk of recurrence but might increase the risk of haemorrhagic complications. Aim: To estimate the safety and efficacy of early initiation of DOACs compared to late guideline-based initiation in people with AIS related to AF. Methods and design: An international, multicentre, randomised (1:1) controlled, two-arm, open, assessor-blinded trial is being conducted. Early treatment is defined as DOAC initiation within 48 h of a minor or moderate stroke, or at day 6–7 following major stroke. Late treatment is defined as DOAC initiation after day 3–4 following minor stroke, after day 6–7 following moderate stroke and after day 12–14 following major stroke. Severity of stroke is defined according to imaging assessment of infarct size. Sample size: ELAN will randomise 2000 participants 1:1 to early versus late initiation of DOACs. This assumes a risk difference of 0.5% favouring the early arm, allowing an upper limit of the 95% confidence interval up to 1.5% based on the Miettinen & Nurminen formula. Outcomes: The primary outcome is a composite of symptomatic intracranial haemorrhage, major extracranial bleeding, recurrent ischaemic stroke, systemic embolism or vascular death at 30 ± 3 days after randomisation. Secondary outcomes include the individual components of the primary outcome at 30 ± 3 and 90 ± 7 days and functional status at 90 ± 7 days. Discussion: ELAN will estimate whether there is a clinically important difference in safety and efficacy outcomes following early anticoagulation with a DOAC compared to late guideline-based treatment in neuroimaging-selected people with an AIS due to AF.
AB - Rationale: Direct oral anticoagulants (DOAC) are highly effective in preventing ischaemic strokes in people with atrial fibrillation (AF). However, it is unclear how soon they should be started after acute ischaemic stroke (AIS). Early initiation may reduce early risk of recurrence but might increase the risk of haemorrhagic complications. Aim: To estimate the safety and efficacy of early initiation of DOACs compared to late guideline-based initiation in people with AIS related to AF. Methods and design: An international, multicentre, randomised (1:1) controlled, two-arm, open, assessor-blinded trial is being conducted. Early treatment is defined as DOAC initiation within 48 h of a minor or moderate stroke, or at day 6–7 following major stroke. Late treatment is defined as DOAC initiation after day 3–4 following minor stroke, after day 6–7 following moderate stroke and after day 12–14 following major stroke. Severity of stroke is defined according to imaging assessment of infarct size. Sample size: ELAN will randomise 2000 participants 1:1 to early versus late initiation of DOACs. This assumes a risk difference of 0.5% favouring the early arm, allowing an upper limit of the 95% confidence interval up to 1.5% based on the Miettinen & Nurminen formula. Outcomes: The primary outcome is a composite of symptomatic intracranial haemorrhage, major extracranial bleeding, recurrent ischaemic stroke, systemic embolism or vascular death at 30 ± 3 days after randomisation. Secondary outcomes include the individual components of the primary outcome at 30 ± 3 and 90 ± 7 days and functional status at 90 ± 7 days. Discussion: ELAN will estimate whether there is a clinically important difference in safety and efficacy outcomes following early anticoagulation with a DOAC compared to late guideline-based treatment in neuroimaging-selected people with an AIS due to AF.
KW - Atrial fibrillation
KW - DOAC
KW - acute ischaemic stroke
KW - anticoagulation
KW - timing
UR - http://www.scopus.com/inward/record.url?scp=85132278262&partnerID=8YFLogxK
U2 - 10.1177/23969873221106043
DO - 10.1177/23969873221106043
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 36478762
AN - SCOPUS:85132278262
SN - 2396-9873
VL - 7
SP - 487
EP - 495
JO - European Stroke Journal
JF - European Stroke Journal
IS - 4
ER -
