International Journal of Cardiology 179 (2015) 288–291
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Antithrombotic therapy for atrial fibrillation in patients with acute ischemic stroke or transient ischemic attack Poh-Shiow Yeh a, Chun-Ming Yang a, Sheng-Hsiang Lin b, Wei-Ming Wang c, Po-Sheng Chen b,d, Huey-Juan Lin a, Kao-Chang Lin a, Chia-Yu Chang a, Tain-Junn Cheng a,e, Yi-Heng Li d,⁎ a
Department of Neurology, Chi-Mei Medical Center, Tainan, Taiwan Institute of Clinical Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan Biostatistics Consulting Center, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan d Department of Internal Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan e Department of Occupational Safety and Health, Institute of Industrial Safety and Disaster Prevention, College of Sustainable Environment, Chia Nan University of Pharmacy and Science, Tainan, Taiwan b c
a r t i c l e
i n f o
Article history: Received 28 October 2014 Accepted 4 November 2014 Available online 13 November 2014 Keywords: Atrial fibrillation Ischemic stroke Warfarin
Although warfarin is more effective than are antiplatelet drugs for preventing stroke in patients with atrial fibrillation (AF), it is usually underutilized after stroke for various reasons. A global AF registry study indicated that warfarin was prescribed even less frequently for stroke prevention in Asia than in the West [1]. The major problem of using warfarin in Asian populations is the increased risk of intracranial bleeding. The purpose of this study was to evaluate the use of antithrombotic therapy at discharge in a consecutive cohort of patients with acute ischemic stroke or transient ischemic attack (TIA) and AF. From August 2006 to December 2012, we prospectively recruited patients with acute ischemic stroke or TIA admitted to our hospital who met the following 3 criteria: (1) age 18 years or older, (2) had AF based on a 12-lead electrocardiogram obtained at admission, and (3) no rheumatic heart disease or prosthetic heart valve based on the patient's clinical history and echocardiographic examination. According to a predetermined protocol, the clinical data were collected from each patient. CHADS2, CHA2DS2-VASc, and ATRIA bleeding scores before stroke were calculated. Oral antithrombotic therapy and modified Rankin Scale (mRS) score were recorded at discharge. Antithrombotic therapy included antiplatelet and anticoagulation drugs. Aspirin, clopidogrel, dipyridamole, ticlopidine and cilostazol were defined as
⁎ Corresponding author at: Department of Internal Medicine, National Cheng Kung University Hospital, 138 Sheng Li Road, Tainan 704, Taiwan. E-mail address: [email protected] (Y.-H. Li).
http://dx.doi.org/10.1016/j.ijcard.2014.11.102 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
antiplatelet drugs. Warfarin was the only oral anticoagulant drug used in this study because non-vitamin K antagonist oral anticoagulants (NOACs) were not available in our hospital during the study period. Patients were followed up at our outpatient clinics. If patients did not attend the clinics, follow up information was obtained by research assistants who made telephone calls to patients or their families. The clinical outcome assessed in this study was a composite endpoint of all-cause death, recurrent ischemic stroke or TIA, or the occurrence of ischemic heart disease, whichever came first. Each patient was followed up until the day one of the components of the composite endpoint occurred or until December 31, 2012, whichever came first. The percentage of PT INR in therapeutic range was calculated as the number of PT INR results in therapeutic range (2–3) divided by the total number of PT INR examinations. This study protocol was approved by the human research committee of our hospital and written informed consent was obtained from each study participant. A total of 749 patients (mean age 73.7 years, 45% male) with acute ischemic stroke or TIA and AF were included. Before admission, 68% of the patients had not had any antithrombotic therapy at baseline, 25% had taken antiplatelet drugs, and 7% had taken warfarin (±antiplatelet drugs). At discharge, 22% of the patients still had not had any antithrombotic therapy, 38% were prescribed antiplatelet drugs and 40% were given warfarin (± antiplatelet drugs). The clinical characteristics of the patients were summarized in Table 1. Older patients were given less warfarin and more antiplatelet drugs (Fig. 1A). The higher the CHADS2 score (Fig. 1B), CHA2DS2-VASc score (Fig. 1C), mRS score (Fig. 1D) and ATRIA bleeding score (Fig. 1E), the lower was the likelihood that a patient would be given warfarin. The most important independent predictor that a patient will not be given any antithrombotic therapy at discharge was an mRS score ≥ 3 (Table 2A). The mean follow up period was 4.0 ± 9.7 months. For patients who took warfarin, the mean percentage of PT INR in therapeutic range was 24.3 ± 16.7%. PT INR in the therapeutic range N60% was 3%, 45–60% was 11%, and b45% was 86%. The Kaplan–Meier analysis showed a significantly worse clinical outcome in the patients without taking any antithrombotic therapy (Fig. 2). In multivariate Cox regression analysis, after adjusting for all clinical factors, an mRS score ≥ 3 at discharge was a significant independent risk factor of the composite endpoint (Table 2B). Patients treated with warfarin (HR, 0.27; 95% CI 0.19–0.39) or antiplatelet drugs
P.-S. Yeh et al. / International Journal of Cardiology 179 (2015) 288–291
289
Table 1 Demographic and clinical characteristics of patients with nonvalvular atrial fibrillation based on prescribed antithrombotic therapy at discharge. Variable
None (n = 163)
Antiplatelet (n = 282)
Anticoagulant (n = 204)
Anticoagulant and antiplatelet (n = 100)
p value
Age (years) Male Hypertension Diabetes mellitus Smoking Previous stroke Ischemic heart disease Congestive heart failure CHADS2 score 0–1 2 ≥3 CHA2DS2-VASc score 0–1 2–3 ≥4 mRS score b3 ≥3 ATRIA bleeding score b4 ≥4
75.1 ± 10.1 80 (49) 128 (79) 76 (47) 51 (31) 56 (34) 37 (23) 29 (18) 2.7 ± 1.5 34 (21) 41 (25) 88 (54) 4.3 ± 1.8 10 (6) 80 (49) 74 (45) 5 (4–6) 26 (16) 137 (84) 3 (1–6) 105 (64) 58 (36)
76.1 ± 10.7 132 (47) 227 (81) 100 (35)⁎⁎ 79 (28) 84 (30) 63 (23) 48 (17) 2.5 ± 1.4 74 (26) 78 (28) 130 (46) 4.1 ± 1.7⁎⁎ 14 (5) 160 (57) 108 (38) 4 (2–5)⁎⁎ 88 (31) 194 (69) 3 (1–4) 197 (70) 85 (30)
71.0 ± 11.2⁎⁎ 86 (42) 137 (67)⁎⁎ 61 (30)⁎⁎ 64 (31) 69 (34) 28 (14) 35 (17) 2.2 ± 1.4⁎⁎
70.3 ± 10.3⁎⁎ 36 (36) 76 (76) 25 (25)⁎⁎ 39 (39) 26 (26) 18 (18) 13 (13) 2.1 ± 1.3⁎⁎
b0.001⁎ 0.147 0.006⁎ 0.001⁎ 0.243 0.405 0.071 0.759 b0.001⁎
71 (35) 52 (25) 81 (40) 3.5 ± 1.8⁎⁎ 28 (14) 116 (57) 60 (29) 3 (1–4)⁎⁎ 99 (49) 105 (51) 2 (1–3)⁎⁎ 168 (82) 36 (18)
39 (39) 28 (28) 33 (33) 3.3 ± 1.8⁎⁎ 13 (13) 63 (63) 24 (24) 2 (1–3)⁎⁎ 75 (75) 25 (25) 1 (1–3)⁎⁎ 87 (87) 13 (13)
0.006
b0.001⁎ b0.001 b0.001⁎ b0.001⁎ b0.001⁎ b0.001⁎
Data are presented as mean ± standard deviation, median (interquartile range), and number (percentage). Categorical variables were compared using the chi-square test; continuous variables were analyzed using ANOVA. ATRIA indicates anticoagulation and risk factors in atrial fibrillation; CHADS2, congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus and prior stroke; CHA2DS2-VASc, congestive heart failure, hypertension, age, diabetes mellitus, prior stroke, vascular disease, age 65–74 years, and gender category; mRS, modified Rankin Scale. Anticoagulant, defined as warfarin use at discharge; antiplatelet, defined as aspirin, clopidogrel, dipyridamole, ticlopidine or cilostazol at discharge. The intergroup comparisons were performed using chi-square test for categorical variables and unpaired Student's t test or analysis of variance (ANOVA) for continuous variables. ⁎ Indicates significant p value in multiple group comparison. ⁎⁎ p b 0.05 compared with patients with none of anticoagulant and antiplatelet use at discharge.
(HR, 0.51; 95% CI 0.38–0.69) had a significantly lower risk of the composite endpoint (Table 2B). The most important factor in our study for not using any antithrombotic therapy at discharge was the patient's mRS score. Post-stroke severe disability and high risk of falls are common reasons for not using warfarin in patients with ischemic stroke and AF [2]. However, previous studies demonstrated that warfarin reduced post-stroke mortality in patients with AF, and this beneficial effect was independent of age and stroke severity [3,4]. The survival benefit of NOACs in patients with high mRS scores is still unsettled because patients with severe disabling stroke were excluded in NOAC clinical trials. Therefore, judicious warfarin use should still be considered for patients with a high post-stroke mRS score and AF. For those who are unable to take anticoagulants for any reason, at least antiplatelet drugs should be given regardless of their stroke severity. In conclusion, the prescription rate and time in therapeutic range of warfarin were low in our study cohort, which reflected the real world practice of treating stroke patients with AF in Taiwan. Increased bleeding risk was the major concern that prevented the use of warfarin. Post-stroke functional disability was the most important factor that predicted no antithrombotic therapy in patients
with ischemic stroke or TIA in AF and also the most important poor prognostic indicator. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] J. Oldgren, J.S. Healey, M. Ezekowitz, et al., Variations in cause and management of atrial fibrillation in a prospective registry of 15,400 emergency department patients in 46 countries: the RE-LY Atrial Fibrillation Registry, Circulation 129 (2014) 1568–1576. [2] J. Somerfield, P.A. Barber, N.E. Anderson, et al., Not all patients with atrial fibrillationassociated ischemic stroke can be started on anticoagulant therapy, Stroke 37 (2006) 1217–1220. [3] K.N. Vemmos, G. Tsivgoulis, K. Spengos, et al., Anticoagulation influences long-term outcome in patients with nonvalvular atrial fibrillation and severe ischemic stroke, Am. J. Geriatr. Pharmacother. 2 (2004) 265–273. [4] K.K. Andersen, T.S. Olsen, Reduced poststroke mortality in patients with stroke and atrial fibrillation treated with anticoagulants: results from a Danish quality-control registry of 22,179 patients with ischemic stroke, Stroke 38 (2007) 259–263.
290
P.-S. Yeh et al. / International Journal of Cardiology 179 (2015) 288–291
Fig. 1. Distribution of antithrombotic therapy in patients with ischemic stroke or transient ischemic attack in atrial fibrillation at discharge based on (A) age, (B) CHADS2 score, (C) CHA2DS2-VASc score, (D) mRS score, and (E) ATRIA bleeding score.
P.-S. Yeh et al. / International Journal of Cardiology 179 (2015) 288–291
291
Table 2A Multivariate logistic regression analyses for predictors that patients will not be given any antithrombotic therapy at discharge. Univariate OR (95% CI) Age (years) Male (vs. female) Hypertension Diabetes mellitus Smoking Previous stroke Ischemic heart disease Congestive heart failure CHADS2 score 2 (vs. 0–1) ≥3 (vs. 0–1) CHA2DS2-VASc score 2–4 (vs. 0–1) ≥4 (vs. 0–1) mRS score ≥3 (vs. b3) ATRIA bleeding score ≥4 (vs. b4)
Multivariate model 1 p value
OR (95% CI)
1.02 (1.00, 1.03) 1.26 (0.89, 1.78) 1.21 (0.80, 1.84) 1.88 (1.32, 2.68) 1.01 (0.70, 1.47) 1.19 (0.82, 1.72) 0.30 (0.04, 2.29) 1.11 (0.70, 1.75)
0.065 0.193 0.364 0.001 0.955 0.354 0.243 0.670
1.40 (0.85, 2.32) 1.95 (1.26, 3.03)
0.185 0.003
1.30 (0.63, 2.66) 2.09 (1.01, 4.32)
0.476 0.046
4.26 (2.72, 6.68)
b0.001
3.86 (2.43, 6.12)
1.86 (1.28, 2.71)
0.001
1.47 (0.99, 2.19)
Multivariate model 2 p value
1.58 (1.06, 2.36)
0.024⁎
0.91 (0.53, 1.56) 1.02 (0.61, 1.71)
0.724 0.927
OR (95% CI)
p value
1.59 (1.08, 2.34)
0.019⁎
0.91 (0.43, 1.93) 0.96 (0.43, 2.11)
0.802 0.909
b0.001⁎
3.85 (2.42, 6.11)
b0.001⁎
0.057
1.48 (0.99, 2.20)
0.055
CI, confidence interval; OR, odds ratio; other abbreviations are the same as for Table 1. ⁎ Indicates significant p value in multivariate logistic regression analysis.
Fig. 2. Kaplan–Meier curve for probability of disease-free survival stratified by different antithrombotic therapy at discharge.
Table 2B Univariate and multivariate Cox regression analyses for predictors of the composite endpoint. Univariate
Age (years) Male (vs. female) Hypertension Diabetes mellitus Smoking Previous stroke Ischemic heart disease Congestive heart failure CHADS2 score 2 (vs. 0–1) ≥3 (vs. 0–1) CHA2DS2-VASc score 2–4 (vs. 0–1) ≥4 (vs. 0–1) mRS score ≥ 3 (vs. b3) Antithrombotic drug at discharge Anticoagulant (vs. none) Antiplatelet (vs. none) Both (vs. none) Antihypertensive drug at discharge Antidiabetic drug at discharge
Multivariate model 1
Multivariate model 2
HR (95% CI)
p value
HR (95% CI)
1.03 (1.02, 1.05) 1.39 (1.10, 1.75) 1.11 (0.84, 1.46) 1.07 (0.84, 1.36) 1.01 (0.70, 1.47) 1.08 (0.84, 1.39) 4.51 (2.58, 7.91) 1.17 (0.87, 1.59) 1.09 (1.00, 1.18) 1.20 (0.86, 1.66) 1.43 (1.08, 1.91) 1.12 (1.05, 1.20) 2.47 (1.34, 4.56) 3.28 (1.77, 6.08) 2.10 (1.61, 2.73)
b0.001 0.006 0.480 0.588 0.955 0.533 b0.001 0.304 0.040 0.283 0.014 b0.001 0.004 b0.001 b0.001
1.00 (0.98, 1.01) 1.21 (0.94, 1.55)
0.818 0.147
1.31 (0.74, 2.31)
0.354
0.87 (0.62, 1.23) 1.17 (0.86, 1.61)
0.442 0.319
0.35 (0.25, 0.48) 0.44 (0.33, 0.58) 0.33 (0.21, 0.50) 0.83 (0.65, 1.07) 0.81 (0.61, 1.08)
b0.001 b0.001 b0.001 0.150 0.155
CI, confidence interval; HR, hazard ratio; other abbreviations are the same as for Table 1. ⁎ Indicates significant p value in multivariate Cox regression analysis.
p value
HR (95% CI)
p value
1.00 (0.98, 1.01) 1.13 (0.88, 1.47)
0.637 0.342
0.403 0.243 0.007⁎ b0.001⁎ b0.001⁎ b0.001⁎
1.51 (1.10, 2.05)
0.010⁎
1.31 (0.70, 2.47) 1.50 (0.76, 2.97) 1.53 (1.13, 2.08)
0.27 (0.19, 0.39) 0.51 (0.38, 0.69) 0.30 (0.18, 0.48)
b0.001⁎ b0.001⁎ b0.001⁎
0.29 (0.20, 0.41) 0.52 (0.39, 0.69) 0.31 (0.19, 0.51)
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Antithrombotic therapy for atrial fibrillation in patients with acute ischemic stroke or transient ischemic attack Poh-Shiow Yeh a, Chun-Ming Yang a, Sheng-Hsiang Lin b, Wei-Ming Wang c, Po-Sheng Chen b,d, Huey-Juan Lin a, Kao-Chang Lin a, Chia-Yu Chang a, Tain-Junn Cheng a,e, Yi-Heng Li d,⁎ a
Department of Neurology, Chi-Mei Medical Center, Tainan, Taiwan Institute of Clinical Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan Biostatistics Consulting Center, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan d Department of Internal Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan e Department of Occupational Safety and Health, Institute of Industrial Safety and Disaster Prevention, College of Sustainable Environment, Chia Nan University of Pharmacy and Science, Tainan, Taiwan b c
a r t i c l e
i n f o
Article history: Received 28 October 2014 Accepted 4 November 2014 Available online 13 November 2014 Keywords: Atrial fibrillation Ischemic stroke Warfarin
Although warfarin is more effective than are antiplatelet drugs for preventing stroke in patients with atrial fibrillation (AF), it is usually underutilized after stroke for various reasons. A global AF registry study indicated that warfarin was prescribed even less frequently for stroke prevention in Asia than in the West [1]. The major problem of using warfarin in Asian populations is the increased risk of intracranial bleeding. The purpose of this study was to evaluate the use of antithrombotic therapy at discharge in a consecutive cohort of patients with acute ischemic stroke or transient ischemic attack (TIA) and AF. From August 2006 to December 2012, we prospectively recruited patients with acute ischemic stroke or TIA admitted to our hospital who met the following 3 criteria: (1) age 18 years or older, (2) had AF based on a 12-lead electrocardiogram obtained at admission, and (3) no rheumatic heart disease or prosthetic heart valve based on the patient's clinical history and echocardiographic examination. According to a predetermined protocol, the clinical data were collected from each patient. CHADS2, CHA2DS2-VASc, and ATRIA bleeding scores before stroke were calculated. Oral antithrombotic therapy and modified Rankin Scale (mRS) score were recorded at discharge. Antithrombotic therapy included antiplatelet and anticoagulation drugs. Aspirin, clopidogrel, dipyridamole, ticlopidine and cilostazol were defined as
⁎ Corresponding author at: Department of Internal Medicine, National Cheng Kung University Hospital, 138 Sheng Li Road, Tainan 704, Taiwan. E-mail address: [email protected] (Y.-H. Li).
http://dx.doi.org/10.1016/j.ijcard.2014.11.102 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
antiplatelet drugs. Warfarin was the only oral anticoagulant drug used in this study because non-vitamin K antagonist oral anticoagulants (NOACs) were not available in our hospital during the study period. Patients were followed up at our outpatient clinics. If patients did not attend the clinics, follow up information was obtained by research assistants who made telephone calls to patients or their families. The clinical outcome assessed in this study was a composite endpoint of all-cause death, recurrent ischemic stroke or TIA, or the occurrence of ischemic heart disease, whichever came first. Each patient was followed up until the day one of the components of the composite endpoint occurred or until December 31, 2012, whichever came first. The percentage of PT INR in therapeutic range was calculated as the number of PT INR results in therapeutic range (2–3) divided by the total number of PT INR examinations. This study protocol was approved by the human research committee of our hospital and written informed consent was obtained from each study participant. A total of 749 patients (mean age 73.7 years, 45% male) with acute ischemic stroke or TIA and AF were included. Before admission, 68% of the patients had not had any antithrombotic therapy at baseline, 25% had taken antiplatelet drugs, and 7% had taken warfarin (±antiplatelet drugs). At discharge, 22% of the patients still had not had any antithrombotic therapy, 38% were prescribed antiplatelet drugs and 40% were given warfarin (± antiplatelet drugs). The clinical characteristics of the patients were summarized in Table 1. Older patients were given less warfarin and more antiplatelet drugs (Fig. 1A). The higher the CHADS2 score (Fig. 1B), CHA2DS2-VASc score (Fig. 1C), mRS score (Fig. 1D) and ATRIA bleeding score (Fig. 1E), the lower was the likelihood that a patient would be given warfarin. The most important independent predictor that a patient will not be given any antithrombotic therapy at discharge was an mRS score ≥ 3 (Table 2A). The mean follow up period was 4.0 ± 9.7 months. For patients who took warfarin, the mean percentage of PT INR in therapeutic range was 24.3 ± 16.7%. PT INR in the therapeutic range N60% was 3%, 45–60% was 11%, and b45% was 86%. The Kaplan–Meier analysis showed a significantly worse clinical outcome in the patients without taking any antithrombotic therapy (Fig. 2). In multivariate Cox regression analysis, after adjusting for all clinical factors, an mRS score ≥ 3 at discharge was a significant independent risk factor of the composite endpoint (Table 2B). Patients treated with warfarin (HR, 0.27; 95% CI 0.19–0.39) or antiplatelet drugs
P.-S. Yeh et al. / International Journal of Cardiology 179 (2015) 288–291
289
Table 1 Demographic and clinical characteristics of patients with nonvalvular atrial fibrillation based on prescribed antithrombotic therapy at discharge. Variable
None (n = 163)
Antiplatelet (n = 282)
Anticoagulant (n = 204)
Anticoagulant and antiplatelet (n = 100)
p value
Age (years) Male Hypertension Diabetes mellitus Smoking Previous stroke Ischemic heart disease Congestive heart failure CHADS2 score 0–1 2 ≥3 CHA2DS2-VASc score 0–1 2–3 ≥4 mRS score b3 ≥3 ATRIA bleeding score b4 ≥4
75.1 ± 10.1 80 (49) 128 (79) 76 (47) 51 (31) 56 (34) 37 (23) 29 (18) 2.7 ± 1.5 34 (21) 41 (25) 88 (54) 4.3 ± 1.8 10 (6) 80 (49) 74 (45) 5 (4–6) 26 (16) 137 (84) 3 (1–6) 105 (64) 58 (36)
76.1 ± 10.7 132 (47) 227 (81) 100 (35)⁎⁎ 79 (28) 84 (30) 63 (23) 48 (17) 2.5 ± 1.4 74 (26) 78 (28) 130 (46) 4.1 ± 1.7⁎⁎ 14 (5) 160 (57) 108 (38) 4 (2–5)⁎⁎ 88 (31) 194 (69) 3 (1–4) 197 (70) 85 (30)
71.0 ± 11.2⁎⁎ 86 (42) 137 (67)⁎⁎ 61 (30)⁎⁎ 64 (31) 69 (34) 28 (14) 35 (17) 2.2 ± 1.4⁎⁎
70.3 ± 10.3⁎⁎ 36 (36) 76 (76) 25 (25)⁎⁎ 39 (39) 26 (26) 18 (18) 13 (13) 2.1 ± 1.3⁎⁎
b0.001⁎ 0.147 0.006⁎ 0.001⁎ 0.243 0.405 0.071 0.759 b0.001⁎
71 (35) 52 (25) 81 (40) 3.5 ± 1.8⁎⁎ 28 (14) 116 (57) 60 (29) 3 (1–4)⁎⁎ 99 (49) 105 (51) 2 (1–3)⁎⁎ 168 (82) 36 (18)
39 (39) 28 (28) 33 (33) 3.3 ± 1.8⁎⁎ 13 (13) 63 (63) 24 (24) 2 (1–3)⁎⁎ 75 (75) 25 (25) 1 (1–3)⁎⁎ 87 (87) 13 (13)
0.006
b0.001⁎ b0.001 b0.001⁎ b0.001⁎ b0.001⁎ b0.001⁎
Data are presented as mean ± standard deviation, median (interquartile range), and number (percentage). Categorical variables were compared using the chi-square test; continuous variables were analyzed using ANOVA. ATRIA indicates anticoagulation and risk factors in atrial fibrillation; CHADS2, congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus and prior stroke; CHA2DS2-VASc, congestive heart failure, hypertension, age, diabetes mellitus, prior stroke, vascular disease, age 65–74 years, and gender category; mRS, modified Rankin Scale. Anticoagulant, defined as warfarin use at discharge; antiplatelet, defined as aspirin, clopidogrel, dipyridamole, ticlopidine or cilostazol at discharge. The intergroup comparisons were performed using chi-square test for categorical variables and unpaired Student's t test or analysis of variance (ANOVA) for continuous variables. ⁎ Indicates significant p value in multiple group comparison. ⁎⁎ p b 0.05 compared with patients with none of anticoagulant and antiplatelet use at discharge.
(HR, 0.51; 95% CI 0.38–0.69) had a significantly lower risk of the composite endpoint (Table 2B). The most important factor in our study for not using any antithrombotic therapy at discharge was the patient's mRS score. Post-stroke severe disability and high risk of falls are common reasons for not using warfarin in patients with ischemic stroke and AF [2]. However, previous studies demonstrated that warfarin reduced post-stroke mortality in patients with AF, and this beneficial effect was independent of age and stroke severity [3,4]. The survival benefit of NOACs in patients with high mRS scores is still unsettled because patients with severe disabling stroke were excluded in NOAC clinical trials. Therefore, judicious warfarin use should still be considered for patients with a high post-stroke mRS score and AF. For those who are unable to take anticoagulants for any reason, at least antiplatelet drugs should be given regardless of their stroke severity. In conclusion, the prescription rate and time in therapeutic range of warfarin were low in our study cohort, which reflected the real world practice of treating stroke patients with AF in Taiwan. Increased bleeding risk was the major concern that prevented the use of warfarin. Post-stroke functional disability was the most important factor that predicted no antithrombotic therapy in patients
with ischemic stroke or TIA in AF and also the most important poor prognostic indicator. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] J. Oldgren, J.S. Healey, M. Ezekowitz, et al., Variations in cause and management of atrial fibrillation in a prospective registry of 15,400 emergency department patients in 46 countries: the RE-LY Atrial Fibrillation Registry, Circulation 129 (2014) 1568–1576. [2] J. Somerfield, P.A. Barber, N.E. Anderson, et al., Not all patients with atrial fibrillationassociated ischemic stroke can be started on anticoagulant therapy, Stroke 37 (2006) 1217–1220. [3] K.N. Vemmos, G. Tsivgoulis, K. Spengos, et al., Anticoagulation influences long-term outcome in patients with nonvalvular atrial fibrillation and severe ischemic stroke, Am. J. Geriatr. Pharmacother. 2 (2004) 265–273. [4] K.K. Andersen, T.S. Olsen, Reduced poststroke mortality in patients with stroke and atrial fibrillation treated with anticoagulants: results from a Danish quality-control registry of 22,179 patients with ischemic stroke, Stroke 38 (2007) 259–263.
290
P.-S. Yeh et al. / International Journal of Cardiology 179 (2015) 288–291
Fig. 1. Distribution of antithrombotic therapy in patients with ischemic stroke or transient ischemic attack in atrial fibrillation at discharge based on (A) age, (B) CHADS2 score, (C) CHA2DS2-VASc score, (D) mRS score, and (E) ATRIA bleeding score.
P.-S. Yeh et al. / International Journal of Cardiology 179 (2015) 288–291
291
Table 2A Multivariate logistic regression analyses for predictors that patients will not be given any antithrombotic therapy at discharge. Univariate OR (95% CI) Age (years) Male (vs. female) Hypertension Diabetes mellitus Smoking Previous stroke Ischemic heart disease Congestive heart failure CHADS2 score 2 (vs. 0–1) ≥3 (vs. 0–1) CHA2DS2-VASc score 2–4 (vs. 0–1) ≥4 (vs. 0–1) mRS score ≥3 (vs. b3) ATRIA bleeding score ≥4 (vs. b4)
Multivariate model 1 p value
OR (95% CI)
1.02 (1.00, 1.03) 1.26 (0.89, 1.78) 1.21 (0.80, 1.84) 1.88 (1.32, 2.68) 1.01 (0.70, 1.47) 1.19 (0.82, 1.72) 0.30 (0.04, 2.29) 1.11 (0.70, 1.75)
0.065 0.193 0.364 0.001 0.955 0.354 0.243 0.670
1.40 (0.85, 2.32) 1.95 (1.26, 3.03)
0.185 0.003
1.30 (0.63, 2.66) 2.09 (1.01, 4.32)
0.476 0.046
4.26 (2.72, 6.68)
b0.001
3.86 (2.43, 6.12)
1.86 (1.28, 2.71)
0.001
1.47 (0.99, 2.19)
Multivariate model 2 p value
1.58 (1.06, 2.36)
0.024⁎
0.91 (0.53, 1.56) 1.02 (0.61, 1.71)
0.724 0.927
OR (95% CI)
p value
1.59 (1.08, 2.34)
0.019⁎
0.91 (0.43, 1.93) 0.96 (0.43, 2.11)
0.802 0.909
b0.001⁎
3.85 (2.42, 6.11)
b0.001⁎
0.057
1.48 (0.99, 2.20)
0.055
CI, confidence interval; OR, odds ratio; other abbreviations are the same as for Table 1. ⁎ Indicates significant p value in multivariate logistic regression analysis.
Fig. 2. Kaplan–Meier curve for probability of disease-free survival stratified by different antithrombotic therapy at discharge.
Table 2B Univariate and multivariate Cox regression analyses for predictors of the composite endpoint. Univariate
Age (years) Male (vs. female) Hypertension Diabetes mellitus Smoking Previous stroke Ischemic heart disease Congestive heart failure CHADS2 score 2 (vs. 0–1) ≥3 (vs. 0–1) CHA2DS2-VASc score 2–4 (vs. 0–1) ≥4 (vs. 0–1) mRS score ≥ 3 (vs. b3) Antithrombotic drug at discharge Anticoagulant (vs. none) Antiplatelet (vs. none) Both (vs. none) Antihypertensive drug at discharge Antidiabetic drug at discharge
Multivariate model 1
Multivariate model 2
HR (95% CI)
p value
HR (95% CI)
1.03 (1.02, 1.05) 1.39 (1.10, 1.75) 1.11 (0.84, 1.46) 1.07 (0.84, 1.36) 1.01 (0.70, 1.47) 1.08 (0.84, 1.39) 4.51 (2.58, 7.91) 1.17 (0.87, 1.59) 1.09 (1.00, 1.18) 1.20 (0.86, 1.66) 1.43 (1.08, 1.91) 1.12 (1.05, 1.20) 2.47 (1.34, 4.56) 3.28 (1.77, 6.08) 2.10 (1.61, 2.73)
b0.001 0.006 0.480 0.588 0.955 0.533 b0.001 0.304 0.040 0.283 0.014 b0.001 0.004 b0.001 b0.001
1.00 (0.98, 1.01) 1.21 (0.94, 1.55)
0.818 0.147
1.31 (0.74, 2.31)
0.354
0.87 (0.62, 1.23) 1.17 (0.86, 1.61)
0.442 0.319
0.35 (0.25, 0.48) 0.44 (0.33, 0.58) 0.33 (0.21, 0.50) 0.83 (0.65, 1.07) 0.81 (0.61, 1.08)
b0.001 b0.001 b0.001 0.150 0.155
CI, confidence interval; HR, hazard ratio; other abbreviations are the same as for Table 1. ⁎ Indicates significant p value in multivariate Cox regression analysis.
p value
HR (95% CI)
p value
1.00 (0.98, 1.01) 1.13 (0.88, 1.47)
0.637 0.342
0.403 0.243 0.007⁎ b0.001⁎ b0.001⁎ b0.001⁎
1.51 (1.10, 2.05)
0.010⁎
1.31 (0.70, 2.47) 1.50 (0.76, 2.97) 1.53 (1.13, 2.08)
0.27 (0.19, 0.39) 0.51 (0.38, 0.69) 0.30 (0.18, 0.48)
b0.001⁎ b0.001⁎ b0.001⁎
0.29 (0.20, 0.41) 0.52 (0.39, 0.69) 0.31 (0.19, 0.51)
