Fatal intracranial haemorrhage occurring after oral anticoagulant treatment initiation for secondary stroke prevention in patients with atrial fibrillation

G Tsivgoulis; A H Katsanos; D J Seiffge; M Paciaroni; D Wilson; M Koga; K Macha; M Cappellari; B Kallmünzer; A A Polymeris; K Toyoda; V Caso; D J Werring; S T Engelter; G M De Marchis; RAF, RAF-DOAC, CROMIS-2, SAMURAI, NOACISP, Erlangen, Verona registry collaborators

doi:10.1111/ene.14280

Fatal intracranial haemorrhage occurring after oral anticoagulant treatment initiation for secondary stroke prevention in patients with atrial fibrillation

Eur J Neurol. 2020 Aug;27(8):1612-1617. doi: 10.1111/ene.14280. Epub 2020 May 17.

Authors

G Tsivgoulis^{1

2}, A H Katsanos³, D J Seiffge^{4

5

6}, M Paciaroni⁷, D Wilson⁵, M Koga⁸, K Macha⁹, M Cappellari¹⁰, B Kallmünzer⁹, A A Polymeris⁴, K Toyoda⁸, V Caso⁷, D J Werring⁵, S T Engelter^{4

11}, G M De Marchis⁴; RAF, RAF-DOAC, CROMIS-2, SAMURAI, NOACISP, Erlangen, Verona registry collaborators

Affiliations

¹ Second Department of Neurology, National and Kapodistrian University of Athens School of Medicine, Attikon' University Hospital, Athens, Greece.
² Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA.
³ Division of Neurology, McMaster University/Population Health Research Institute, Hamilton, ON, Canada.
⁴ Neurology and Stroke Center, University Hospital and University of Basel, Basel, Switzerland.
⁵ Stroke Research Center, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, UK.
⁶ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁷ Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Perugia, Italy.
⁸ Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
⁹ Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.
¹⁰ Stroke Unit, Department of Neuroscience, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
¹¹ Neurorehabilitation Unit, University Center for Medicine of Aging and Rehabilitation Basel, Felix Platter Hospital, University of Basel, Switzerland.

PMID: 32333493
DOI: 10.1111/ene.14280

Abstract

Background and purpose: In this pooled analysis of seven multicentre cohorts potential differences were investigated in the incidence, characteristics and outcomes between intracranial haemorrhages (ICHs) associated with the use of non-vitamin K antagonist oral anticoagulants (NOAC-ICH) or with vitamin K antagonists (VKA-ICH) in ischaemic stroke patients after oral anticoagulant treatment initiation for atrial fibrillation (AF).

Methods: Data from 4912 eligible AF patients who were admitted in a stroke unit with ischaemic stroke or transient ischaemic attack and who were treated with either VKAs or NOACs within 3 months post-stroke were included. Fatal ICH was defined as death occurring during the first 30 days after ICH onset. A meta-analysis of available observational studies reporting 30-day mortality rates from NOAC-ICH or VKA-ICH onset was additionally performed.

Results: During 5970 patient-years of follow-up 71 participants had an ICH, of whom 20 were NOAC-ICH and 51 VKA-ICH. Patients in the two groups had comparable baseline characteristics, except for the higher prevalence of kidney disease in VKA-ICH patients. There was a non-significant higher number of fatal ICH in patients with VKAs (11 events per 3385 patient-years) than in those with NOACs (three events per 2623 patient-years; hazard ratio 0.32, 95% confidence interval 0.09-1.14). Three-month functional outcomes were similar (P > 0.2) in the two groups. The meta-analysis showed a lower 30-day mortality risk for patients with NOAC-ICH compared to VKA-ICH (relative risk 0.70, 95% confidence interval 0.51-0.95).

Conclusions: Non-vitamin K oral anticoagulants for intracranial haemorrhages and VKA-ICH occurring during secondary stroke prevention of AF patients have comparable baseline characteristics and outcomes except for the risk of fatal ICH within 30 days, which might be greater in VKA-ICH.

Keywords: anticoagulation; cerebral haemorrhage; cerebral infarction; cerebrovascular diseases and cerebral circulation; neurological disorders.

Publication types

Meta-Analysis

MeSH terms

Administration, Oral
Anticoagulants / adverse effects
Atrial Fibrillation* / complications
Atrial Fibrillation* / drug therapy
Brain Ischemia* / drug therapy
Humans
Intracranial Hemorrhages / chemically induced
Intracranial Hemorrhages / epidemiology
Stroke* / complications
Stroke* / drug therapy
Stroke* / epidemiology
Vitamin K / therapeutic use

Substances

Anticoagulants
Vitamin K