A survey of reasons for continuing warfarin therapy in the era of direct oral anticoagulants in Japanese patients with atrial fibrillation: the SELECT study

Figures & data

Figure 1 Flowchart of questions about physician recommendations to switch to DOACs or continue warfarin.

Notes: For each patient, physicians were asked Q1 to distinguish between patients who had received a recommendation to switch to DOACs and those who had not. For the former, physicians were then asked Q2 and Q3 to identify the underlying reason for the recommendation and the reason that the patient did not comply with the recommendation. For the latter, physicians were asked Q4 to identify the reason for not recommending switching from warfarin to DOACs.
Abbreviation: DOAC, direct oral anticoagulant.

Table 1 Patient demographic and clinical characteristics

	Total (N=313)	<70 years old (N=83)	≥70 years old (N=230)	P-valuea
Male gender	197 (62.9)	65 (78.3)	132 (57.4)	<0.001
Age (years)	76.4±9.6	64.3±4.9	80.8±6.6	<0.001
Weight (kg)	61.2±12.7 (N=252)	71.2±11.5 (N=63)	57.9±11.3 (N=189)	<0.001
Creatinine clearance (mL/min)	57.3±28.0 (N=250)	87.8±24.8 (N=62)	47.2±20.8 (N=188)	<0.001
Duration of warfarin therapy
<5 years	85 (27.2)	22 (26.5)	63 (27.4)	0.876
≥5 years	228 (72.8)	61 (73.5)	167 (72.6)
HAS-BLED score	2.6±1.2	2.1±1.2	2.7±1.1	<0.001
CHADS2 score	2.3±1.2	1.5±0.8	2.6±1.1	<0.001
CHA2 DS2-VASc score	4.1±1.8	2.7±1.4	4.6±1.7	<0.001
INR at baseline	2.0±0.4 (N=308)	2.0±0.5 (N=80)	2.0±0.4 (N=228)	1.000
FIR (%)	66.0±28.5 (N=309)	47.3±29.6 (N=81)	72.7±25.0 (N=228)	<0.001
Patients achieving therapeutic goals	209 (67.9) (N=308)	39 (48.8) (N=80)	170 (74.6) (N=228)	<0.001
Number of concomitant drugs	6.1±3.3	5.0±2.8	6.5±3.3	<0.001
Frequency of INR measurement (per year)	9.0±3.9 (N=309)	8.2±3.6 (N=81)	9.2±3.9 (N=228)	0.044
Percentage of patients whose warfarin dosages were changed in the past 1 year	41.2	36.1	43.0	0.274
Self-pay ratio to whole medical costs
0%	25 (8.0)	3 (3.6)	22 (9.6)	<0.001
10%	165 (52.7)	2 (2.4)	163 (70.9)
20%	19 (6.1)	1 (1.2)	18 (7.8)
30%	102 (32.6)	76 (91.6)	26 (11.3)
Others	2 (0.6)	1 (1.2)	1 (0.4)

Notes: Data are presented as N (%) or mean ± SD. The number of patients used for the analysis was 313, 83, and 230 for total patients, patients aged <70 years, and patients aged ≥70 years, respectively, unless otherwise specified. In patients with NVAF, target INR level is within the following range according to Japanese treatment guidelines (Guidelines for Pharmacotherapy of Atrial Fibrillation [JCS 2013]): 2.0–3.0 for patients <70 years old and 1.6–2.6 for patients ≥70 years old.²¹ CHADS₂ score was calculated based on age >75 years and the presence of congestive heart failure, hypertension, diabetes, and 2 points for stroke or transient ischemic attack. CHA₂DS₂-VASc score was calculated by allotting 1 point each for congestive heart failure/left ventricular dysfunction, hypertension, diabetes, vascular disease (prior myocardial infarction, peripheral arterial disease, or aortic plaque), age between 65 and 74 years, and female gender; 2 points each were allotted for age >75 years and prior stroke, or transient ischemic attack. HAS-BLED score was calculated based on the following components: hypertension, abnormal renal function, abnormal liver function, previous stroke, bleeding history or predisposition, labile INR, age >65 years, drugs predisposing patient to bleeding (antiplatelet agents or nonsteroidal anti-inflammatory drugs), and alcohol abuse.

a Comparison between patients <70 years old and those ≥70 years old. An unpaired t-test and a chi-square test were used for continuous variables and categorical variables, respectively.

Abbreviations: FIR, frequency in therapeutic range; INR, international normalized ratio; NVAF, nonvalvular atrial fibrillation.

Figure 2 INR values when doses of warfarin were increased or decreased in patients <70 years old and ≥70 years old.

Notes: Mean ± SD is shown. Blue = patients aged <70 years; red = patients aged ≥70 years. Dotted lines show the therapeutic ranges recommended by the Japanese treatment guidelines for each age range.
Abbreviation: INR, international normalized ratio.

Table 2 Reasons physicians recommended switching to DOACs (N=161)

	n (%)
Medical reasons
Unstable INR	19 (11.8)
Interaction with other drugs	1 (0.6)
High bleeding risk	11 (6.8)
Better safety and efficacy profile of DOACs	89 (55.3)
Concomitant disease	0 (0)
Reduction of overall risk accompanied with warfarin therapy	2 (1.2)
Bleeding during warfarin therapy	0 (0)
Timing of dental procedure	1 (0.6)
Timing of ablation	0 (0)
Timing of surgical procedure	0 (0)
Pregnancy	0 (0)
Other medical reasons	1 (0.6)
Nonmedical reasons
To avoid regular INR measurement	21 (13)
To avoid food restrictions	13 (8.1)
Dose adjustment of warfarin is bothersome	2 (1.2)
To reduce total number of pills	0 (0)
Other nonmedical reasons	1 (0.6)

Note: Data are presented as n (%).

Abbreviations: DOAC, direct oral anticoagulant; INR, international normalized ratio.

Table 3 Reasons in favor of continued warfarin therapy (N=152)

	n (%)
Medical reasons
INR stably controlled	57 (37.5)
Decreased renal function	39 (25.7)
No bleeding or ischemic events while taking warfarin	8 (5.3)
Concerns about bleeding and embolic events during switch	2 (1.3)
Frequent dose adjustments required	3 (2.0)
Other medical reasons	6 (3.9)
Nonmedical reasons
Higher medical costs of DOACs compared to warfarin	11 (7.2)
Patients were satisfied with warfarin therapy	9 (5.9)
Patients had concerns about switching	13 (8.6)
INR measurement motivates patients to continue therapy	0 (0)
Other nonmedical reasons	2 (1.3)
Other reasons	2 (1.3)

Note: Data are presented as n (%).

Abbreviations: DOAC, direct oral anticoagulant; INR, international normalized ratio.

Table 4 Physicians’ perspective on patients suitable for warfarin treatment (N=38)

Characteristics	n (%)
Decreased renal function	31 (81.6)
Low body weight	16 (42.1)
INR within the recommended therapeutic range	20 (52.6)
No stroke events with INR below the therapeutic range	4 (10.5)
Patient satisfied with warfarin	26 (68.4)
Frequent dose adjustments required	10 (26.3)
Self-pay ratio of medical costs: 0%	0 (0.0)
Self-pay ratio of medical costs: 10%	0 (0.0)
Self-pay ratio of medical costs: 20%	1 (2.6)
Self-pay ratio of medical costs: 30%	16 (42.1)
NVAF patients with coronary artery disease	0 (0.0)
NVAF patients with mitral valve stenosis	22 (57.9)
NVAF patients with valvular disease	7 (18.4)
Other	3 (7.9)

Note: Data are presented as n (%).

Abbreviations: INR, international normalized ratio; NVAF, nonvalvular atrial fibrillation.

Table 5 Physicians’ perspective on patients suitable for switching to DOACs (N=38)

Characteristics	n (%)
All patients for whom DOACs are indicated are suitable	9 (23.7)
INR consistently outside the therapeutic range	29 (76.3)
Fluctuations in INR	34 (89.5)
Inadequate dietary restriction	31 (81.6)
Dehydration	4 (10.5)
Patients aged <65 years	8 (21.1)
Patients aged ≥65 and <75 years	10 (26.3)
Patients aged ≥75 years	8 (21.1)
Diabetes mellitus	4 (10.5)
Concomitant treatment with NSAIDs	8 (21.1)
Concomitant treatment with antiplatelet drug	12 (31.6)
Patients requiring surgery	18 (47.4)
Patients scheduled for ablation treatment	16 (42.1)
Patients scheduled for dental procedure	6 (15.8)
Dementia	10 (26.3)
Depression	1 (2.6)
Self-pay ratio of medical costs: 0%	11 (28.9)
Self-pay ratio of medical costs: 10%	12 (31.6)
Self-pay ratio of medical costs: 20%	4 (10.5)
Self-pay ratio of medical costs: 30%	2 (5.3)
Other	0 (0.0)

Note: Data are presented as n (%).

Abbreviations: DOAC, direct oral anticoagulant; INR, international normalized ratio; NSAID, nonsteroidal anti-inflammatory drug.

Table 6 Demographic and clinical characteristics of patients receiving continued warfarin therapy (current study) and patients who switched to apixaban (AGAIN study³⁸)

	SELECT (N=313)	AGAIN (N=697)	P-value
Male gender	197 (62.9)	433 (62.1)	0.8045
Age (years)	76.4±9.6	76.2±9.1	0.6816
Weight (kg)	61.2±12.7 (N=252)	60.6±12.6 (N=572)	0.5245
Creatinine clearance (mL/min)	57.3±28.0 (N=250)	60.8±43.0 (N=331)	0.2551
HAS-BLED score	2.6±1.2	2.6±1.1	1.000
CHADS2 score	2.3±1.2	2.5±1.3	0.1171
CHA2 DS2-VASc score	4.1±1.8	4.0±1.7	0.2877
INR at baseline	2.0±0.4 (N=308)	2.0±0.6 (N=672)	0.4718
FIR (%)	66.0±28.5 (N=309)	60.2±30.4 (N=672)	0.004
Patients achieving therapeutic goals
<70 years	39 (48.8) (N=80)	55 (38.7) (N=142)	0.1477
≥70 years	170 (74.6) (N=228)	304 (57.4) (N=530)	<0.0001
Duration of warfarin therapy
<5 years	85 (27.2)	261 (37.4)	<0.0001
≥5 years	228 (72.8)	326 (46.8)
Self-pay ratio of total medical costs
0%	25 (8.0)	104 (14.9)	<0.0001
10%	165 (52.7)	411 (59.0)
20%	19 (6.1)	42 (6.0)
30%	102 (32.6)	139 (19.9)
Other	2 (0.6)	1 (0.1)

Notes: Data are presented as N (%) or mean ± SD. The number of the patients used for the analysis was 313 for the SELECT study (current study) and 697 for the AGAIN study, unless otherwise specified. In patients with NVAF, INR levels should be maintained within the following ranges according to Japanese treatment guidelines (Guidelines for Pharmacotherapy of Atrial Fibrillation [JCS 2013]): 2.0–3.0 for patients <70 years old and 1.6–2.6 for patients ≥70 years old.²¹ CHADS₂ score was calculated based on age >75 years and the presence of congestive heart failure, hypertension, diabetes, and 2 points for stroke or transient ischemic attack. CHA₂DS₂-VASc score was calculated by allotting 1 point each for congestive heart failure/left ventricular dysfunction, hypertension, diabetes, vascular disease (prior myocardial infarction, peripheral arterial disease, or aortic plaque), age between 65 and 74 years, and female gender; 2 points each were allotted for age >75 years and prior stroke, transient ischemic attack, or thromboembolism. HAS-BLED score was calculated based on the following components: hypertension, abnormal renal function, abnormal liver function, previous stroke, bleeding history or predisposition, labile INR, age >65, drugs predisposing to bleeding (antiplatelet agents or nonsteroidal anti-inflammatory drugs), and alcohol abuse.

Abbreviations: FIR, frequency in therapeutic range; INR, international normalized ratio; NVAF, nonvalvular atrial fibrillation.

JCS Joint Working GroupGuidelines for Pharmacotherapy of Atrial Fibrillation (JCS 2013)Circ J20147881997202124965079

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