Non-vitamin K-dependent Oral Anticoagulants Have a Positive Impact on Ischaemic Stroke Severity in Patients With Atrial Fibrillation

Simon Hellwig; Ulrike Grittner; Heinrich Audebert; Matthias Endres; Karl Georg Haeusler


Europace. 2018;20(4):569-574. 

In This Article

Abstract and Introduction


Aims Several studies showed reduced stroke severity in patients with atrial fibrillation (AF) if the international normalized ratio (INR) was ≥ 2 at stroke onset. There are no respective data for non-vitamin K-dependent oral anticoagulants (NOACs). The aim of this study was to compare the impact of NOAC or phenprocoumon intake on stroke severity.

Methods and results In this single-centre observational study, 3669 patients with acute ischaemic stroke were retrospectively analysed regarding AF status and medication immediately before admission. Using multivariable regression, we analysed the association of pre-admission anticoagulation with severe stroke (National Institutes of Health Stroke Scale score ≥ 11) on admission and poor outcome at discharge (modified Rankin scale score > 2). Before the index stroke, 655 patients had known AF and a CHA2DS2-VASc score ≥ 2. While 325 (49.6%) patients were anticoagulated, 159 (24.3%) were prescribed a NOAC and 75 (11.5%) phenprocoumon patients had an INR ≥ 2 on admission. Compared with AF patients without medical stroke prevention, an INR ≥ 2 [OR 0.23 (95% CI 0.10–0.53)] or NOAC intake [OR 0.48 (95% CI 0.27–0.86)] were associated with a lower probability of severe stroke after adjustment for confounders, while an INR < 2 [OR 0.62 (95% CI 0.33–1.16)] was not. Adjusted odds ratios for poor functional outcome at hospital discharge were 0.47 (95% CI 0.27–0.84) for NOAC patients, 0.33 (95% CI 0.17–0.65) for INR ≥ 2 and 0.61 (95% CI 0.32–1.16) for INR < 2.

Conclusion NOAC intake before stroke did reduce the probability of severe stroke on hospital admission and poor functional outcome at hospital discharge as similarly demonstrated for phenprocoumon patients with an INR ≥ 2 on admission.


Non-valvular atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. AF increases the individual stroke risk about four- to five-fold, and at least 15% of all ischaemic strokes are caused by AF. Oral anticoagulation significantly reduces the risk of (recurrent) stroke in patients with AF, and relevant guidelines strongly recommend oral anticoagulation in AF patients with at least one additional risk factor for stroke.[1–3] Four phase III studies have demonstrated that non-vitamin K-dependent oral anticoagulants (NOACs) are at least equally effective to the vitamin K antagonist (VKA) warfarin with a median time in therapeutic range between 58 and 68% in these trials.[4] However, the use of oral anticoagulants is restricted by contraindications such as renal failure or previous bleeds. In addition, the feared risk of bleeding leads to non-compliance with guideline recommendations.[5,6] Consecutively, only a subset of all acute ischaemic stroke patients with known AF before stroke is (sufficiently) anticoagulated when stroke occurs, as demonstrated in multiple observational studies.[7,8] Insufficient long-term persistence to VKAs or NOACs is another major problem in stroke patients.[9,10] While platelet inhibitors are a cornerstone of secondary stroke prevention in non-AF patients, they are no longer recommended by current guidelines for stroke prevention in AF patients.[1–3]

Stroke in patients with AF is more often disabling and associated with increased morbidity and mortality compared with stroke in patients without AF.[11] In addition to the reduction of stroke risk, the intake of VKA reduces stroke severity and improves long-term outcome if the international normalized ratio (INR) is within therapeutic range at stroke onset.[8,12] One could argue that there might be a similar effect of pre-admission NOAC intake on stroke-related morbidity and mortality but there is—besides a retrospective analysis including nine patients with NOAC intake before ischaemic stroke—no published analysis so far.[13,14] Interestingly, recently published experimental data showed a beneficial effect of rivaroxaban pre-treatment on stroke severity in rats.[15] Consequently, we analysed this assumption in a cohort of stroke patients consecutively admitted at our department within 3 years.