Table 1:
Summary of studies on early initiation of anticoagulant treatment in patients with recent atrial fibrillation-related ischaemic stroke
| Study population | Patients’ median age, median stroke severity, and infarctsize* | Median timing of anticoagulation administration initiation | Follow-up period | Recurrent ischaemic stroke† | Intracranial haemorrhage† | |
|---|---|---|---|---|---|---|
| Observational studies with clinical follow-up of ≥3 months | ||||||
| Seiffge et al44 (NOACISP) |
204 (155 DOAC treated) | 79 years; NIHSS score 4; no information on infarct size | 5 days (≤7 days for 65% [n=100] of DOAC-treated patients) | At least 3 months | 7·7% per year (5·1% per year for DOAC administration ≤7days vs 9·3% per year for DOAC administration >7days, p=0.53) | 1·3% per year |
| Arihiro et al45 (SAMURAI-NVAF) |
1192 (466 DOAC treated) | 78 years; NIHSS score 3; 24% small, 48% medium, and 28% large infarcts | 5 days for DOAC | 5 days for DOAC | 8·5% per year (VKA) and 10·1% per year (DOAC, p>0.05) | 1·2% per year (VKA) vs 0·8% per year (DOAC) |
| Paciaroni et al46 (RAF-NOAC) |
1127 (all DOAC treated) | 76 years;NIHSS score 8; 41% small, 33% medium, and 22% large infarcts | No overall median reported (8 days for dabigatran and rivaroxaban, 7 days for apixaban) | 3 months | 7·8% per year | 6·4% per year |
| Wilson et al51 | 1355 (475 DOAC) | 76 years; NIHSS score 4; 18% large infarcts | 11 days (≤4 days for 26% [n=358] of patients) | 90 days | 5·7% per year (combined DOAC and VKA) | 0.6% per year (combined DOAC and VKA) |
| Observational studies with clinical follow-up within 3 months or with surrogate outcome imaging markers | ||||||
| Macha et al47 | 243 (all DOAC treated) | 78 years; NIHSS score 5; 17% small infarct or TIA, 70% medium, and 13% large infarcts | From 1·7 days for small infarct or TlA to 6·7 days for large infarcts (≤7 days for 89·7% [n=218] of DOAC-treated patients) | In hospital | Not reported | 1 case of symptomatic and 2 cases of asymptomatic intracranial haemorrhage |
| Cappellari et al48 | 147 (all DOAC treated) | 79 years; NIHSS score 8; 54% small, 22% medium, and 24% large infarcts | 3·3 days (≤3 days for 66% [n=97] of patients; ≤7 days for all patients) | CT scan at 7 days | No case observed | 8 cases of asymptomatic intracranial haemorrhage (7 new, 1 before DOAC treatment) |
| Gioia et al49 | 60 (all rivaroxaban treated) | 74 years; NIHSS score 2; median DWI lesion volume 7·9 mL | 3 days | MRI scan at 7 days | 1 case | No cases of symptomatic intracranial haemorrhage, 8 cases of asymptomatic petechial haemorrhage |
| Deguchi et al50 | 300 (186 DOAC treated) | 77 years; NIHSS score 7; no information on infarct size | 3 days for DOAC, 7days for VKA | In hospital | No case observed | 2 cases of intracranial haemorrhage, 1 case of extracranial haemorrhage |
| Observational studies with a majority of patients receiving VKAs or heparins | ||||||
| Abdul-Rahim et al40 | 1300 (no DOAC-treated patients) | 73 years; NIHSS score 14; no information on infarct size | 2 days | 90 days | 8·2% of patients (107 events in 1300 patients) | 2·3% of patients had symptomatic intracranial haemorrhage (30 events in 1300 patients) |
| Paciaroni et al29 | 1029 (93 DOAC treated) | 77 years; NIHSS score 9; 37% small, 36% medium, and 27% large infarct | 8·5 days for DOAC, 12·1 days for VKA | 3 months | 77 events (including TIA and systemic embolism) | 37 events (including major extracranial haemorrhages) |
| Randomised controlled trials with patients receiving DOACs | ||||||
| Hong et al41 | 195 (95 rivaroxaban treated) | 70 years; NIHSS score 2; median DWI lesion volume 2·6 mL | 2 days | MRI scan at 4 weeks | 1 case | 30 new haemorrhagic lesions (all asymptomatic) |
DOAC=direct oral anticoagulant. NIHSS=National Institutes of Health Stroke Scale. VKA=vitamin K antagonist. TIA=transient ischaemic attack. DWI=diffusion weighted imaging.
Although definitions of infarct size might differ slightly between studies, small infarct size was commonly defined by lesions smaller than 1·5 cm in the anterior or posterior circulation; medium infarct size by lesions in a cortical superficial branch of middle cerebral artery (MCA), in the MCA deep branch, in the internal border zone territories, in a cortical superficial branch of posterior cerebral artery, or in a cortical superficial branch of the anterior cerebral artery; large infarct size by lesions that involve the complete territory of MCA, posterior cerebral artery, or anterior cerebral artery, in two cortical superficial branches of MCA, in a cortical superficial branch of MCA associated to the MCA deep branch, or in more than one artery territory.
Annualised event frequencies (% per year) were calculated whenever possible using published data (number of observed events divided by follow-up period).