The TIMING Investigators
Guidelines do not provide evidence-based recommendations on the optimal time-point to start non-vitamin K antagonist oral anticoagulants (NOAC) after acute ischemic stroke in patients with atrial fibrillation (AF). We investigated the efficacy and safety of early vs. delayed initiation of NOAC.
The TIMING study was a registry-based, randomised, non-inferiority, open-label, blinded endpoint study at 34 out of 72 stroke units in Sweden. The Swedish Stroke Register, with an integrated computerised randomisation module, was used for enrolment and follow-up. Patients were within 72 hours from stroke onset randomised (1:1) to early (≤4 days) or delayed (5-10 days) initiation of NOAC. Primary outcome was the composite of recurrent ischemic stroke, symptomatic intracerebral haemorrhage, or all-cause mortality within 90 days. In parallel, a control cohort of patients with acute ischemic stroke and AF receiving early or delayed NOAC within 10 days (without randomisation) was registered.
From April 2017 to December 2020, 888 patients, 78 years (mean), 46% females, were randomized in TIMING, and 9,321 control patients 79 years (mean), 46% females, were registered. Follow-up was at least 90 days for all patients.
This study addresses the important clinical dilemma of NOAC initiation after ischemic stroke in patients with AF. The integration of a randomisation module in the Swedish Stroke Register combines the advantages of a prospective randomised study design with the strengths of a comprehensive clinical register, with the addition of a large control cohort. Study results will be presented at the European Stroke Organisation Conference.
ClinicalTrials.gov Identifier: NCT02961348.