The effectiveness of direct oral anticoagulant therapy on stroke severity and functional prognosis for very elderly cardioembolic stroke patients at high bleeding risk

Abstract

Listen

Translate article

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 <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.