ONLINE APPENDIX
Online Table 1
Diagnoses, procedures, and pharmacotherapy used for defining the study population, comorbidity,
and outcomes
Study population
Heart failure
Defined from diagnosis of
ICD8: 425, 4270, 4271
hypertensive, cardiomyopathy
ICD10: I110, I50, I42, J81
(including dilated and obstructive
cardiomyopathy), acute pulmonary
oedema, decompensated and
unspecified heart failure.
Vascular disease
Defined from diagnosis of myocardial ICD8: 410, 440
ICD10: I21, I22, I700, I702-I709
infarction, peripheral arterial disease
and aortic plaque orcoronary
NCSP: KFN
procedures
Atrial fibrillation
Defined from diagnosis
ICD8: 42793, 42794
ICD10: I48
Comorbidity
CHA2DS2-VASc and HAS-BLED scores
Defined from diagnosis of
Previous
ischemic stroke, transient ischemic
thrombosis*
attack, pulmonary embolus, or
arterial embolus
Hypertension
ICD8: 444, 450, 433, 434, 435, 436,
437, 438
ICD10: I63, I64, I26, I74, G458, G459
Defined from combination
Treatment: Adrenergic α-antagonist,
treatment with a least two classes
non-loop-diuretics, vasodilators, beta-
of antihypertensive drugs. This
blockers, calcium channel blockers, and
definition of hypertension has a
renin-angiotensin system inhibitors.
positive predictive value of 80.0%
and a specificity 94.7%1
Diabetes mellitus
Defined from glucose-lowering
ATC: A10
medication
Alcohol abuse
Defined from diagnosis and
ICD8: 291, 303
Liver disease
adverse alcohol consumption
ICD10: E244, E52, F1, G312, G621,
reported during hospitalization
G721, I426, K292, K70, K860, L278A,
Defined from diagnoses of liver
cancer, chronic liver disease, liver
O354, T51, Z714, Z721
ICD8: 070, 155, 571-573
ICD10: B15-B19, C22, D684C, I982B,
K70-K77, DQ618A, Z944
surgery, cirrhosis, and hepatitis or
NCSP: KJJC
liver procedure
Chronic renal
Defined from diagnosis of chronic
failure
glomerulonephritis, chronic
tubulointestinal nephropathy, nonend-stage chronic kidney disease,
and diabetic and hypertensive
nephropathy. Previously validated2.
Previous bleeding
Defined from diagnosis of
gastrointestinal, intracranial,
respiratory, and urinary tract
bleedings; and anemia caused by
ICD8: 403-404, 581-584,25002,40039,
59009, 59320, 75310-11, 75319
ICD10: E102, E112, E132, E142, I120,
M200, M313, M319, M321B, N02-N08,
N11-N12, N14, N18-N19, N26, N158N160, N162-N164, N168, Q612-Q613,
Q615, Q619
ICD8: 430-431, N852-N853
ICD10: I60-I62, I690-I692, J942, K250,
K254, K260, K264, K270, K280, K920K922, N02, R04, R31, S064-S066
bleeding.
Pharmacotherapy
Antiplatelet
Defined from ATC codes of aspirin
ATC: B01AC06, B01AC04, N02BA01
or clopidogrel
Vitamin K
Defined from ATC codes of warfarin
ATC: B01AA03, B01AA04
antagonist
or marcoumar
Renin-
Defined from ATC code
ATC: C09
Beta-blockers
Defined from ATC code
ATC: C07
Loop-diuretics
Defined from ATC code
ATC: C03C
Statins
Defined from ATC code
ATC: C10A
Spironolactone
Defined from ATC code
ATC: C03D
angiotensin
system inhibitors
Glucose-lowering Defined from ATC code
medication
ATC: A10
NSAID
Defined from ATC code
ATC: M01A
Outcomes
Thromboembolism
Death from or diagnosis of
ICD10: I63-I64, G458-G459, I74
ischemic stroke, transient ischemic
attack, or arterial embolism
Bleeding
Death from or diagnosis of
ICD10: I60-I62, I690-I692, J942,
gastrointestinal, intracranial,
K250, K254, K260, K264, K270,
respiratory, and urinary tract
K280, K920-K922, N02, R04,
bleedings; and anemia caused by
R31, S064-S066,
bleeding.
Heart failure
Hospitalization of heart failure
ICD10: I110, I42, I50, J819
Myocardial
Coronary death or diagnosis of
ICD10: I21-22, I20-I25 (coronary
infarction
myocardial infarction
death).
hospitalization
(secondary)
(secondary)
ICD8:
ICD10:
NCSP:
8th revision of the International Classification of Diseases system
10th revision of the International Classification of Diseases system
The Nordic Medical Statistics Committees Classification of Surgical Procedures
* For HAS-BLED only stroke isincluded in the score.
Reference
1: Olesen JB, Lip GY, Hansen ML et al. Validation of risk stratification schemes for predicting
stroke and thromboembolism in patients with atrial fibrillation: Nationwide cohort study. BMJ.
2011;342:d124
2: Hommel K, Rasmussen S, Madsen M, Kamper AL: The Danish Registry on Regular Dialysis and
Transplantation:completeness and validity of incident patient registration, Nephrol. Dial.
Transplant. 2010, 25 (3): 947-951.
Online Table 2 – Potential indications for antithrombotic therapy in heart failure patients with coexisting vascular disease without atrial fibrillation.
VKA # (%)
No AF patients§ (%) Antiplatelet# (%)
Any indications
4,139 (14.0)
3,124 (13.6)
1,087 (32.5)
Recent venousthromboembolism
622 (2.1)
421 (67.7)
343 (55.1)
Recent arterialembolus
157 (0.5)
113 (72.0)
37 (23.6)
Recent muralthrombus
5 (0.0)
3 (60.0)
4 (80.0)
Valvulardisease
3,436 (11.6)
2,646 (77.0)
751 (21.8)
Previousvalvular procedure
533 (1.8)
410 (76.9)
329 (61.7)
Total
29,660 (100.0)
23,061 (77.8)
3,344 (11.3)
Recent defines within 1 year prior to inclusion. Antiplatelet denotes aspirin or clopidogrel.
Abbreviation: AF, atrial fibrillation; VKA, vitamin K antagonist. § Vertical percentage given of heart
failure patients with co-existing vascular disease and no AF with potential antithrombotic indications,
# Horizontal percentage given of patients on antithrombotic therapy at inclusion according to
indications.
Online Table 3 -Risk of thromboembolism or MI (total events 15,758)
Thromboembolism or MI
AF status
Prevalent AF
Incident AF
Treatment regimen
VKA
plus
antiplatelet
VKA
Single antiplatelet
single
VKA
plus
antiplatelet
VKA
Single antiplatelet
single
IR [95% CI]
HR [95% CI]
13.0 [11.9-14.2]
13.4 [12.3-14.6]
20.1 [19.1-21.1]
1.00 [0.89-1.14]
reference
1.39 [1.26-1.54]
11.2 [11.9-14.2]
12.3 [10.9-13.9]
18.3 [17.2-19.5]
0.97 [0.82-1.14]
reference
1.41 [1.23-1.61]
VKA
plus
single
antiplatelet
13.5 [12.0-15.1]
0.95 [0.84-1.07]
VKA
13.1 [11.6-14.8]
0.88 [0.78-1.00]
Single antiplatelet
14.6 [14.2-14.9]
reference
Adjusted for age, gender, inclusion year, HF severity group and CHA2DS2-VASc.
Abbreviation: IR, crude incidence rate (events per 100 person-years); HR, hazard ratio;
CI, confidence interval; CHA2DS2-VASc, please see text
No AF