The effectiveness of direct oral anticoagulant therapy on stroke severity and functional prognosis for very elderly cardioembolic stroke patients at high bleeding risk
Authors: Saito K , Hagii J , Soma T , Washima S , Yamada N , Shiroto H , Saito S , Kamada T , Takanashi S , Tomita H 
Published: November 2023

Abstract

Background
The All Nippon AF In the Elderly (ANAFIE) Registry showed that taking any DOACs was associated with reduced stroke/systemic embolisms and was not associated with increased major bleeding in very elderly (≥80 years) patients with nonvalvular atrial fibrillation (NVAF) at high bleeding risk (1). However, the relationship between very elderly (≥80 years) cardioembolic stroke (CES) patients with NVAF at high bleeding risk and direct oral anticoagulant (DOAC) therapy before stroke onset remains unknown.

Methods
During a 10-year period from April 2011 to March 2021, 364 CES patients (≥80 years) with NVAF admitted to our hospital within 48 hours after stroke onset and with a modified Rankin Scale (mRS) score of 0 or 1 before onset were studied. High bleeding risk was defined as having any following factors; a bleeding history, renal dysfunction (creatinine clearance &lt;30 ml/min), low body weight (≤45 kg), use of antiplatelet or nonsteroidal anti-inflammatory drugs. They were divided into two groups: high bleeding risk group (H group) (n=214; median 85 years [82-88]; 144 women [67%]) and non-high bleeding risk group (Non-H group) (n=150; median 84 years [82-87]; 69 women [46%]). We compared stroke severity between the two groups and evaluated effect of DOAC treatment on stroke severity and functional outcome.

Results
CHADS₂ score was significantly higher in the H group than in the Non-H group (median 4 [3-4] versus 3 [2-4], p=0.002). NIHSS (National Institutes of Health Stroke Scale) score on admission and proportion of mortality (mRS:6) were relatively higher in H group than in Non-H group, but there were no significant differences among the two groups. However, mRS score at discharge was worse in the H group than in the Non-H group (median 4 [2-5] versus 3 [1-4], p=0.002). The patients in the H group were further divided into three groups based on the treatment with OAC before stroke onset: DOAC therapy (n=20), no-OAC (n=148) and warfarin therapy (n=46). The number of patients with NIHSS (≥8) on admission and mRS (≥5) at discharge were 8 (40%), 104 (70%), and 30 (65%) (p=0.03) and 3 (15%), 60 (41%) and 23 (50%) (p=0.03), respectively. Multivariate analysis confirmed that DOAC therapy had a lower odds ratio (OR) for severe stroke (NIHSS ≥8) on admission (OR to no-OAC=0.22; 95% confidence interval [CI]=0.08-0.62; p=0.005) and poor functional outcome (mRS ≥5) at discharge (OR=0.20; 95% CI=0.05-0.80; p=0.02), when no-OAC was used as a reference after adjusting for confounders.

Conclusion
Very elderly (≥80 years) CES patients with NVAF at high bleeding risk have severe CES than those at non-high bleeding risk. However, DOAC therapy before stroke onset may be associated with reduced stroke severity on admission and poor functional outcome at discharge in very elderly (≥80 years) CES patients with NVAF at high bleeding risk.