Background
Methods
Design
Inclusion and exclusion criteria
Inclusion criteria
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• Adult patients (aged ≥ 18 years) with acute ischemic stroke and atrial fibrillation | |
• Eligible and willing to start (or restart) NOAC | |
• Signed informed consent | |
Exclusion criteria
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• Contraindication to NOAC (e.g. ongoing bleeding, mechanical heart valve prosthesis) | |
• Ongoing therapy with NOAC (without ≥ 2 days interruption at index stroke) | |
• INR > 1.7 | |
• No second brain imaging (CT/MRI) after thrombolysis/thrombectomy | |
• Previous randomisation in the TIMING study |
Randomisation
Outcomes
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Recurrent ischemic stroke within 90 days, defined as a new focal neurological deficit of sudden onset lasting at least 24 h (or < 24 h if following therapeutic intervention, i.e. thrombolysis or thrombectomy, or if the deficit results in death < 24 h), occurring > 24 h after the index ischemic stroke, irrespective of vascular territory and that is not attributable to oedema, brain shift, haemorrhagic transformation, intercurrent illness, hypoxia or drug toxicity [22]; and/or
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Symptomatic ICH within 90 days, defined as a new focal neurological deficit of sudden onset lasting at least 24 h with documented ICH on imaging (CT or MRI). Any intraparenchymal hematoma (≥ 10 mm) will be considered, including haemorrhagic transformation of the index ischemic stroke. However, microhaemorrhages (< 10 mm) do not fulfil the study definition of ICH. ICH will be classified as symptomatic if it is associated with ≥ 4 points increase in total National Institutes of Health stroke scale (NIHSS) or ≥ 2 points increase in 1 of the NIHSS categories [23]; and/or
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Death considered as all-cause mortality within 90 days.
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The individual components of the primary outcome at 90 days and up to 365 days;
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Functional outcome at 90 days as defined by the modified Rankin Scale (mRS);
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Major haemorrhages at 90 days are those that result in death or are life-threatening as defined by the International Society on Thrombosis and Haemostasis (ISTH) [24] or consume major healthcare resources, which include:
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fatal bleeding; and/or
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symptomatic bleeding in a critical area or organ, such as intracranial (including asymptomatic ICH), intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome; and/or
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bleeding causing a fall in haemoglobin level of ≥ 20 g/L, or leading to transfusion of two or more units of whole blood or red cells; and/or
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bleeding events leading to hospitalisation (in addition to the original ISTH definition [24]).
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Adherence/persistence to NOAC therapy at 90 days;
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Days at Acute or Comprehensive Stroke Unit;
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Length of hospital stay within 90 days;
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Re-admission to hospital within 90 days;
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Health economy analysis.