Direct oral anticoagulants compared to vitamin K antagonist in atrial fibrillation -related cerebral ischemia

There is still only limited real-world evidence on comparative effectiveness and safety of direct oral anticoagulants (DOACs) – also referred to as non-vitamin K antagonist oral anticoagulants (NOACs) – versus a vitamin K antagonist in atrial fibrillation. In two studies to fill this gap, DOACs were found to result in a lower risk of intracranial haemorrhage [1,2].

In a retrospective subgroup analysis of the ARISTOPHANES study, stroke/systemic embolism, major bleeding, and their respective components were compared among non-valvular atrial fibrillation patients on DOACs or warfarin [1]. DOACs prescribed were apixaban, dabigatran, or rivaroxaban. Pooled results for two doses were presented: standard NOAC doses and warfarin (5 mg twice-daily apixaban-warfarin, 150 mg twice-daily dabigatran-warfarin, and 20 mg once-daily rivaroxaban-warfarin), and lower NOAC doses and warfarin (2.5 mg twice-daily apixaban-warfarin, 75 mg twice-daily dabigatran-warfarin, and 10 or 15 mg once-daily rivaroxaban-warfarin). All doses of NOACs were associated with lower intracranial haemorrhage rates compared to warfarin. The other main results were as follows:

• Only apixaban was associated with lower rates of stroke/systemic embolism and major bleeding, for both doses compared to warfarin.
• Lower-dose dabigatran patients had similar rates of stroke/systemic embolism and major bleeding compared to warfarin. The standard dose gave similar rates of stroke/systemic embolism, but a lower rate of major bleeding.
• Lower-dose rivaroxaban patients had a similar rate of stroke/systemic embolism compared to warfarin, but the standard-dose was associated with a lower stroke/systemic embolism rate. Lower- as well as standard dose rivaroxaban gave higher major bleeding rates compared to warfarin.

An individual patient data analysis of 7 prospective cohort studies compared clinical outcomes of treatment with DOACs and vitamin K antagonists, among atrial fibrillation patients with a recent ischemic stroke or transient ischemic attack [2]. In this study, DOAC treatment was associated with a reduced risk of poor clinical outcomes, mainly due to a lower risk of intracranial haemorrhage.
The composite primary endpoint was recurrent acute ischemic stroke, intracranial haemorrhage, or mortality.

Of the 4,912 patients included, 2,256 (45.9%) received a vitamin K antagonist and 2,656 (54.1%) a DOAC. The median time from index event (acute ischemic stroke in 97% of cases) to starting vitamin K antagonist as well as DOAC was 5 days (P=0.53). During follow-up of 5,970 patient years, there were 262 acute ischemic stroke (4.4%/year), 71 intracranial haemorrhages (1.2%/year), and 439 deaths (7.4%/year). DOAC use was associated with a reduced risk of the composite endpoint (HR 0.81, P=0.03) and of intracranial haemorrhage (HR 0.42, P<0.01). The risks of recurrent acute ischemic stroke (HR 0.92, P=0.53) and mortality (HR 0.84, P=0.11) were not significantly different.

1. Deitelzweig S, et al. AAN 2019, S35.004.
2. Seiffge D, et al. AAN 2019, S35.007.



Posted on 30 July, 201915 March, 2021