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Association Between Inappropriately Dosed Anticoagulation Therapy With Stroke Severity and Outcomes in Patients With Atrial Fibrillation

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@article{62417b95c90d4351a394c0381829a7de,
title = "Association Between Inappropriately Dosed Anticoagulation Therapy With Stroke Severity and Outcomes in Patients With Atrial Fibrillation",
abstract = "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.",
keywords = "anticoagulation, atrial fibrillation, epidemiology, inappropriate anticoagulation, ischemic stroke",
author = "Vinding, {Naja E} and Butt, {Jawad H} and Olesen, {Jonas B} and Ying Xian and Kristensen, {S{\o}ren Lund} and Rasmus R{\o}rth and Bonde, {Anders Nissen} and Anna Gundlund and Adelina Yafasova and Weeke, {Peter E} and Gislason, {Gunnar H} and Christian Torp-Pedersen and Lars K{\o}ber and Fosb{\o}l, {Emil L}",
year = "2022",
month = mar,
day = "15",
doi = "10.1161/JAHA.121.024402",
language = "English",
volume = "11",
pages = "e024402",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "Wiley-Blackwell",
number = "6",

}

RIS

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

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

UR - http://www.scopus.com/inward/record.url?scp=85126830690&partnerID=8YFLogxK

U2 - 10.1161/JAHA.121.024402

DO - 10.1161/JAHA.121.024402

M3 - Journal article

C2 - 35229642

VL - 11

SP - e024402

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

IS - 6

M1 - e024402

ER -

ID: 75503574