TY - JOUR
T1 - Association Between Inappropriately Dosed Anticoagulation Therapy With Stroke Severity and Outcomes in Patients With Atrial Fibrillation
AU - Vinding, Naja E.
AU - Butt, Jawad H.
AU - Olesen, Jonas B.
AU - Xian, Ying
AU - Kristensen, Søren Lund
AU - Rørth, Rasmus
AU - Bonde, Anders Nissen
AU - Gundlund, Anna
AU - Yafasova, Adelina
AU - Weeke, Peter E.
AU - Gislason, Gunnar H.
AU - Torp-Pedersen, Christian
AU - Køber, Lars
AU - Fosbøl, Emil L.
N1 - Funding Information:
This work was supported by an internal grant from the Department of Cardiology, Copenhagen University Hospital, Copenhagen, Denmark. The funding source did not have influence on any part of the submitted work including the study design; in the collection, analysis, and interpretation of data; in the writing of the report, and in the decision to submit the article for publication.
Publisher Copyright:
© 2022 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
PY - 2022/3/15
Y1 - 2022/3/15
N2 - BACKGROUND: Oral anticoagulation (OAC) is effective for stroke prevention in patients with atrial fibrillation. However, some patients experience stroke despite OAC therapy, and knowledge about the impact of prior treatment quality is lacking. METHODS AND RESULTS: Patients with atrial fibrillation on OAC therapy who had a first-time ischemic stroke were identified in the Danish Stroke Registry (2005–2018). Patients treated with vitamin K antagonist (VKA) therapy were compared according to the international normalized ratio just before stroke (international normalized ratio <2 [subtherapeutic], international normalized ratio 2–3 [therapeutic], international normalized ratio >3 [supratherapeutic]), and patients on underdosed, appropriately dosed, and overdosed direct OAC (DOAC) therapy were compared. Stroke severity was determined using the Scandinavia Stroke Scale (0–58 points), and the risk of very severe stroke (0–14 points) was analyzed by multivariable logistic regression. One-year mortality was determined using multivariable Cox regression. A total of 2319 patients with atrial fibrillation and stroke were included; 1196 were taking a VKA (subtherapeutic [46%], therapeutic [43%], supratherapeutic [11%]), and 1123 were taking DOAC (underdosed [23%], appropriately dosed [60%], and overdosed [17%]). Subtherapeutic and supratherapeutic VKA therapy (compared with therapeutic) and underdosed DOAC therapy (compared with appropriate and underdosed DOAC) patients were older, more often women, and more comorbid. Subtherapeutic VKA therapy was associated with very severe stroke (odds ratio [OR], 2.06 [95% CI, 1.28–3.31]), whereas supratherapeutic VKA therapy was not (OR, 1.24 [95% CI, 0.60– 2.57]) compared with therapeutic VKA therapy. Patients on subtherapeutic and supratherapeutic VKA therapy had a higher 1-year mortality (hazard ratio [HR], 1.66 [95% CI, 1.29–2.13]); HR, 1.55 [95% CI, 1.08–2.22], respectively) than those on therapeutic VKA therapy. Treatment with underdosed or overdosed DOAC therapy was not associated with very severe stroke (OR, 1.27 [95% CI, 0.76–2.15]; OR, 0.73 [95% CI, 0.37–1.43], respectively) and was not associated with 1-year mortality (HR, 1.09 [95% CI, 0.83–1.44]; HR, 0.82 [95% CI, 0.57–1.18], respectively) than appropriate DOAC. CONCLUSIONS: Half of the patients with atrial fibrillation with stroke were on inappropriate OAC therapy. Subtherapeutic VKA was associated with worse stroke severity and higher mortality rate than therapeutic VKA therapy. Neither underdosed nor overdosed DOAC was associated with worse outcomes in adjusted models compared with appropriately dosed DOAC. This study supports DOAC as a first-line therapy over VKA.
AB - BACKGROUND: Oral anticoagulation (OAC) is effective for stroke prevention in patients with atrial fibrillation. However, some patients experience stroke despite OAC therapy, and knowledge about the impact of prior treatment quality is lacking. METHODS AND RESULTS: Patients with atrial fibrillation on OAC therapy who had a first-time ischemic stroke were identified in the Danish Stroke Registry (2005–2018). Patients treated with vitamin K antagonist (VKA) therapy were compared according to the international normalized ratio just before stroke (international normalized ratio <2 [subtherapeutic], international normalized ratio 2–3 [therapeutic], international normalized ratio >3 [supratherapeutic]), and patients on underdosed, appropriately dosed, and overdosed direct OAC (DOAC) therapy were compared. Stroke severity was determined using the Scandinavia Stroke Scale (0–58 points), and the risk of very severe stroke (0–14 points) was analyzed by multivariable logistic regression. One-year mortality was determined using multivariable Cox regression. A total of 2319 patients with atrial fibrillation and stroke were included; 1196 were taking a VKA (subtherapeutic [46%], therapeutic [43%], supratherapeutic [11%]), and 1123 were taking DOAC (underdosed [23%], appropriately dosed [60%], and overdosed [17%]). Subtherapeutic and supratherapeutic VKA therapy (compared with therapeutic) and underdosed DOAC therapy (compared with appropriate and underdosed DOAC) patients were older, more often women, and more comorbid. Subtherapeutic VKA therapy was associated with very severe stroke (odds ratio [OR], 2.06 [95% CI, 1.28–3.31]), whereas supratherapeutic VKA therapy was not (OR, 1.24 [95% CI, 0.60– 2.57]) compared with therapeutic VKA therapy. Patients on subtherapeutic and supratherapeutic VKA therapy had a higher 1-year mortality (hazard ratio [HR], 1.66 [95% CI, 1.29–2.13]); HR, 1.55 [95% CI, 1.08–2.22], respectively) than those on therapeutic VKA therapy. Treatment with underdosed or overdosed DOAC therapy was not associated with very severe stroke (OR, 1.27 [95% CI, 0.76–2.15]; OR, 0.73 [95% CI, 0.37–1.43], respectively) and was not associated with 1-year mortality (HR, 1.09 [95% CI, 0.83–1.44]; HR, 0.82 [95% CI, 0.57–1.18], respectively) than appropriate DOAC. CONCLUSIONS: Half of the patients with atrial fibrillation with stroke were on inappropriate OAC therapy. Subtherapeutic VKA was associated with worse stroke severity and higher mortality rate than therapeutic VKA therapy. Neither underdosed nor overdosed DOAC was associated with worse outcomes in adjusted models compared with appropriately dosed DOAC. This study supports DOAC as a first-line therapy over VKA.
KW - anticoagulation
KW - atrial fibrillation
KW - epidemiology
KW - inappropriate anticoagulation
KW - ischemic stroke
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U2 - 10.1161/JAHA.121.024402
DO - 10.1161/JAHA.121.024402
M3 - Article
C2 - 35229642
AN - SCOPUS:85126830690
SN - 2047-9980
VL - 11
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 6
M1 - e024402
ER -