Abstract | BACKGROUND: METHODS: TIMING (Timing of Oral Anticoagulant Therapy in Acute Ischemic Stroke With Atrial Fibrillation) was a registry-based, randomized, noninferiority, open-label, blinded end-point study at 34 stroke units using the Swedish Stroke Register for enrollment and follow-up. Within 72 hours from stroke onset, patients were randomized to early (≤4 days) or delayed (5-10 days) NOAC initiation, with choice of NOAC at the investigators' discretion. The primary outcome was the composite of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or all-cause mortality at 90 days. The prespecified noninferiority margin was 3%. Secondary outcomes included the individual components of the primary outcome. RESULTS: Between April 2, 2017, and December 30, 2020, 888 patients were randomized to either early (n=450) or delayed (n=438) initiation of NOAC. No patient was lost to 90-day follow-up. Mean age was 78.3 years (SD, 9.9 years); 46.2% were women; 49.1% had previously known atrial fibrillation; and 17.5% prior stroke. The primary outcome occurred in 31 patients (6.89%) assigned to early initiation and in 38 patients (8.68%) assigned to delayed NOAC initiation (absolute risk difference, -1.79% [95% CI, -5.31% to 1.74%]; Pnoninferiority=0.004). Ischemic stroke rates were 3.11% and 4.57% (risk difference, -1.46% [95% CI, -3.98% to 1.07%]) and all-cause mortality rates were 4.67% and 5.71% (risk difference, -1.04% [95% CI, -3.96% to 1.88%]) in the early and delayed groups, respectively. No patient in either group experienced symptomatic intracerebral hemorrhage. CONCLUSIONS: REGISTRATION: URL: http://www. CLINICALTRIALS: gov; Unique identifier: NCT02961348.
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Authors | Jonas Oldgren, Signild Åsberg, Ziad Hijazi, Per Wester, Maria Bertilsson, Bo Norrving, National TIMING Collaborators |
Journal | Circulation
(Circulation)
Vol. 146
Issue 14
Pg. 1056-1066
(10 04 2022)
ISSN: 1524-4539 [Electronic] United States |
PMID | 36065821
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Administration, Oral
- Aged
- Anticoagulants
(adverse effects)
- Atrial Fibrillation
(complications, diagnosis, drug therapy)
- Cerebral Hemorrhage
- Female
- Humans
- Ischemic Stroke
- Male
- Registries
- Stroke
(diagnosis, drug therapy, epidemiology)
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