SUPPLEMENTAL MATERIAL
Table 1: Propensity Score Model Results of Probability of dipeptidyl peptidase-4
inhibitors
Table 2: Subgroup analysis of Risk of All-cause Mortality Among Diabetic Patients
with Pre-existing Heart Failure
Table 3: Subgroup analysis of Risk of Combination of Myocardial Infarction and
Ischemic Stroke Among Diabetic Patients with Pre-existing Heart Failure
Figure legend
Figure 1: Schoenfeld Residuals for Combination of Myocardial Infarction and
Ischemic Stroke in Competing Risk Models
Figure 2: Schoenfeld Residuals for Myocardial Infarction in Competing Risk Models
Figure 3: Schoenfeld Residuals for Ischemic Stroke in Competing Risk Models
Figure 4: Schoenfeld Residuals for Heart failure in Competing Risk Models
Supplementary Table 1. Propensity Score Model Results of Probability of dipeptidyl
peptidase-4 inhibitors
95% CI
Parameter
Estimate Odds Ratios Lower
Upper P value
Age, per year
Male
Year of Index Date
2009
2010
2011
-0.0154
-0.0267
0.985
0.974
0.983
0.943
0.986
1.005
<.0001
0.0982
0.3274
0.5842
1
1.387
1.794
1.314
1.703
1.465
1.89
<.0001
<.0001
2012
2013
Month of Index Date
January
February
March
April
May
June
0.7538
0.7672
2.125
2.154
2.019
2.023
2.236
2.293
<.0001
<.0001
-0.0166
-0.0341
0.0022
-0.0165
-0.0378
1
0.984
0.966
1.002
0.984
0.963
0.91
0.901
0.933
0.917
0.898
1.062
1.036
1.076
1.055
1.033
0.6732
0.3384
0.9517
0.6427
0.2886
0.056
0.0687
0.107
0.0947
0.1453
0.1171
1.058
1.071
1.113
1.099
1.156
1.124
0.98
0.992
1.031
1.019
1.073
1.044
1.142
1.156
1.202
1.186
1.246
1.211
0.1513
0.0777
0.0062
0.0146
0.0001
0.002
-0.0542
0.0179
1
0.947
1.018
0.91
0.984
0.986
1.053
0.008
0.3058
0.0981
1.103
1.011
1.203
0.027
-0.0447
-0.0394
-0.0599
1
0.956
0.961
0.942
0.924
0.891
0.802
0.99
1.038
1.106
0.0111
0.3122
0.4648
July
August
September
October
November
December
Monthly income, NT dollars
Dependent
<19,100
19,10041,999
42,000
Urbanizationa
Level 1
Level 2
Level 3
Level 4 (rural area)
Outpatient Visits of diabetes
specialist, in the past one year
05 visits
1
0.1761
610 visits
0.076
1115 visits
-0.00195
>15 visits
Hospital Level
Level I (Medical center)
-0.1991
Level II
-0.4464
Level III
-1.6854
Level IV
Charlson Comorbidity Index Scoreb 0.0209
Adapted Diabetes Complications
1.193
1.079
0.998
1.136
0.997
0.878
1.252
1.168
1.134
<.0001
0.0591
0.9762
1
0.819
0.64
0.185
1.021
0.788
0.611
0.178
1.012
0.852
0.67
0.194
1.031
<.0001
<.0001
<.0001
<.0001
0.0402
0.1104
1
1.041
1.117
0.995
1.065
1.089
1.171
0.0789
<.0001
0.1333
0.1815
0.1948
0.2395
0.2126
1.143
1.199
1.215
1.271
1.237
1.081
1.122
1.119
1.129
1.042
1.208
1.282
1.319
1.43
1.468
<.0001
<.0001
<.0001
<.0001
0.015
Score 10
Score 11
Duration of diabetes mellitus
Duration of heart failure
History of hospitalization for heart
failure
Anti-hypertensive drug
Alpha-blocker
Beta-blocker
Calcium channel blocker
0.00743
-0.5196
0.0015
0.00218
1.007
0.595
1.002
1.002
0.705
0.303
1.001
1.002
1.44
1.167
1.002
1.002
0.9675
0.1306
<.0001
<.0001
0.0309
1.031
0.997
1.066
0.0701
0.0957
0.1385
-0.0831
1.1
1.149
0.92
1.051
1.113
0.891
1.152
1.185
0.95
<.0001
<.0001
<.0001
Diuretics
ACEI or ARB
Other anti-hypertensive drug
Anti-diabetic drugs
Alpha-glucosidase inhibitor
Sulfonylurea
Insulin
Metformin
Thiazolidinediones
0.1407
0.3756
1.151
1.456
1.115
1.404
1.189
1.509
<.0001
<.0001
0.9022
0.8315
0.7426
0.8542
0.6752
2.465
2.297
2.101
2.349
1.964
2.377
2.222
2.025
2.27
1.877
2.557
2.373
2.181
2.432
2.056
<.0001
<.0001
<.0001
<.0001
<.0001
Severity Index score c
Score 2
Score 3
Score 4
Score 5
Score 6
Score 7
Score 8
Score 9
Other concomitant medications
Antiplatelet agent
Warfarin
Statin
Steroid
NSAID
PPI
Antidepressant
Comorbidities
Hypertension
0.1981
0.0715
0.5116
0.0613
0.1541
0.0632
-0.0176
1.219
1.074
1.668
1.063
1.167
1.065
0.983
1.179
1.013
1.616
1.031
1.122
1.027
0.947
1.261
1.139
1.722
1.097
1.213
1.105
1.02
<.0001
0.0171
<.0001
0.0001
<.0001
0.0007
0.355
-0.0492
0.952
0.892
1.016
0.1411
Peripheal vascular disease
Arterial fibrillation
Liver disease
Cerebrovascular disease
Coronary artery disease
Valvular heart disease
Myocardial infarction
Dyslipidemia
Chronic kidney disease
-0.1662
0.1109
-0.0808
-0.1797
0.847
1.117
0.922
0.836
0.808
1.069
0.893
0.804
0.888
1.167
0.953
0.869
<.0001
<.0001
<.0001
<.0001
0.0262
-0.00877
-0.0171
0.1122
0.0765
1.027
0.991
0.983
1.119
1.079
0.988
0.959
0.942
1.077
1.044
1.067
1.025
1.026
1.162
1.116
0.1803
0.6051
0.4372
<.0001
<.0001
End-stage renal disease
Cancer
Physical limit
Autoimmune disease
0.4197
-0.0995
-0.1649
0.0192
1.522
0.905
0.848
1.019
1.41
0.865
0.813
0.962
1.642
0.948
0.884
1.08
<.0001
<.0001
<.0001
0.5165
a
Urbanization levels in Taiwan are divided into four strata according to the Taiwan National
Health Research Institute publications. Level 1 designates the most urbanized areas, and level
4 designates the least urbanized areas.
b
Charlson Comorbidity Index score is used to determine overall systemic health. With each
increased level of CCI score, there are stepwise increases in the cumulative mortality.
c
Adapted Diabetes Complications Severity Index is a 13-point scale from 7 complication
categories: retinopathy, nephropathy, neuropathy, cerebrovascular, cardiovascular, peripheral
vascular disease, and metabolic, ranging from each complication. Each complication produced
a numeric score ranging from 0 to 2 (0 = no abnormality, 1 = some abnormality, 2 = severe
abnormality).
Abbreviations: SD, standard deviation; NT$, new Taiwan dollars; IQR, interquartile range;
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker;
NSAID, non-steroidal anti-inflammatory drug; PPI, proton pump inhibitor.
Supplementary Table 2. Subgroup analysis of Risk of All-cause Mortality Among
Diabetic Patients with Pre-existing Heart Failure
Hazard Ratio
(95% CI)*
P Value
0.693 (0.650-0.739)
0.642 (0.598-0.688)
<0.001
<0.001
0.095
0.641 (0.577-0.712)
<0.001
0.354
65 years
Hypertension
Yes
No
Myocardial infarction
0.680 (0.645-0.717)
<0.001
0.667 (0.635-0.699)
0.789 (0.619-1.007)
<0.001
<0.001
0.209
Yes
No
Cerebrovascular disease
Yes
No
0.620 (0.563-0.683)
0.683 (0.647-0.721)
<0.001
<0.001
0.082
0.693 (0.651-0.737)
0.640 (0.595-0.688)
<0.001
<0.001
0.115
0.665 (0.621-0.712)
0.674 (0.632-0.719)
<0.001
<0.001
0.729
0.591 (0.537-0.629)
0.702 (0.662-0.745)
<0.001
<0.001
<0.001
0.637 (0.600-0.675)
0.693 (0.640-0.750)
<0.001
<0.001
0.094
Characteristic
Sex
Male
Female
Age
20-64 years
Chronic kidney disease
Yes
No
Using insulin
Yes
No
Previous history of heart failure
Inpatient heart failure
Outpatient heart failure
* Adjusted
for propensity score
Abbreviations: CI, confidence interval.
Interaction
P Value
Supplementary Table 3. Subgroup analysis of Risk of Combination of Myocardial
Infarction and Ischemic Stroke Among Diabetic Patients with Pre-existing Heart Failure
Characteristic
Sex
Male
Female
Age
20-64 years
65 years
Hypertension
Yes
No
Myocardial infarction
Yes
No
Cerebrovascular disease
Yes
No
Chronic kidney disease
Yes
No
Using insulin
Yes
No
Previous history of heart failure
Inpatient heart failure
Outpatient heart failure
* Adjusted
for propensity score
Abbreviations: CI, confidence interval.
Hazard Ratio
(95% CI)*
P Value
Interaction
P Value
0.833 (0.761-0.912)
0.783 (0.709-0.865)
<0.001
<0.001
0.361
0.837 (0.731-0.959)
0.803 (0.743-0.866)
0.010
<0.001
0.514
0.811 (0.758-0.867)
0.813 (0.536-1.234)
<0.001
0.331
0.905
0.802 (0.703-0.914)
0.807 (0.747-0.872)
0.001
<0.001
0.854
0.818 (0.753-0.890)
0.794 (0.711-0.887)
<0.001
<0.001
0.769
0.836 (0.754-0.927)
0.791 (0.725-0.863)
0.001
<0.001
0.508
0.743 (0.665-0.829)
0.831 (0.764-0.904)
<0.001
<0.001
0.151
0.791 (0.726-0.862)
0.804 (0.723-0.893)
<0.001
<0.001
0.696
Supplementary Figure 1. Schoenfeld Residuals for Combination of Myocardial
Infarction and Ischemic Stroke in Competing Risk Models
-.5
0
.5
Test of assumption
0
1
2
3
Time (Years)
4
5
Supplementary Figure 2: Schoenfeld Residuals for Myocardial Infarction in
Competing Risk Models
-.5
0
.5
Test of assumption
0
1
2
3
Time (Years)
4
5
Supplementary Figure 3: Schoenfeld Residuals for Ischemic Stroke in Competing
Risk Models
-.5
0
.5
Test of assumption
0
1
2
3
Time (Years)
4
5
Supplementary Figure 4: Schoenfeld Residuals for Heart failure in Competing
Risk Models
-.5
0
.5
Test of assumption
0
1
2
3
Time (years)
4
5