Risk of severe intracerebral haemorrhage lower with DOACs vs VKAs
Intracerebral haemorrhage (ICH) with direct oral anticoagulants (DOACs) appears to be related to smaller baseline haematoma volumes and less neurological deficit than that with vitamin K antagonists (VKAs), reveals a recent study.
“The results of this cross-sectional study suggest that DOAC-related ICH has a more favourable neuroimaging and clinical profile on hospital admission compared to VKA-related ICH,” said researchers.
“After our results were pooled with the available literature, our pairwise meta-analysis documented a lower in-hospital mortality rate in patients with DOAC-related ICHs,” they added.
In the study sample of 161 consecutive ICH patients (mean age 75.6±9.8 years; 57.8 percent male), 114 had VKA-related ICH while the remaining 47 had DOAC-related ICH. Baseline median ICH volumes (12.8 vs 24.3 cm3; p=0.007) and median admission National Institutes of Health Stroke Scale (NIHSS) scores (8 vs 15; p=0.003) were significantly lower in patients with DOAC-related ICH. [Neurology 2017;89:1142-1151]
Patients with DOAC-related ICH also had significantly lower prevalence of ICH volume >30 cm3 (25.5 vs 45.7 percent; p=0.018), median ICH score (1 vs 2 points; p=0.049) and prevalence of severe ICH (17 vs 36.8 percent; p=0.013).
On the other hand, those with VKA-related ICH were administered significantly more pharmacologic interventions during hospitalization than those with DOAC-related ICH (p<0.01).
DOAC-related ICH patients also showed significantly less prevalent cerebral oedema at 24 hours (53.2 vs 71.0 percent; p=0.03) and midline shift (26.1 vs 45.6 percent; p=0.022) compared with VKA-related ICH patients, according to neuroimaging data.
Multivariable regression analysis showed that DOAC-related ICH was significantly independently associated with lower baseline haematoma volume (linear regression coefficient, -0.596; 95 percent CI, -0.97 to -0.163; p=0.006) and lower risk of severe ICH on admission (odds ratio [OR], 0.34; 0.13 to 0.87; p=0.025).
Investigators also performed a meta-analysis of observational studies from the databases of Medline and Scopus. Pooled data from three eligible studies showed that DOAC-related ICH was significantly associated with lower haematoma volumes at baseline (standardized mean difference, -0.57; -1.02 to -0.12; p=0.01) and in-hospital mortality rate (OR, 0.44; 0.21 to 0.91; p=0.03).
Compared with VKAs, DOACs have a shorter half-life and exert no effect on various mechanisms involved in coagulation, platelet aggregation and prothrombin formation. According to the researchers, this may account for the differential effect of the medications on baseline haematoma volume. [J Clin Pharmacol 2006;46:981-990]
“Another potential explanation for the larger hematoma volume observed in VKA-related ICHs could be the higher risk of both cerebral microbleed (CMB) presence and CMB progression in stroke patients on VKA treatment,” they added. [Neurology 2009;72:171-176; Clin Neurol Neurosurg 2013;115:1682-1685]
Although needing further validation in studies with larger sample sizes, “[t]hese findings underscore DOACs as an attractive therapeutic option in terms of risk of severe ICH in patients with nonvalvular atrial fibrillation and high risk of intracranial bleeding,” noted researchers.