Balance by match method
eFigure 1. Balance of propensity score matching: Averages of standardized mean differences in baseline covariates along surveillance time by match method using caliper 0.25 SD of logit propensity score and prior CVD status for 3 analysis datasets.
standardiz ed mean distance
0.01 0.02 0.03 0.04 0.05 0.06
2008_03_31 2008_06_30 2008_09_30 2008_12_31 2009_03_31 2009_06_30 2009_09_30
: prior_cvd 0 :
ds washout=183, baseline=183
: prior_cvd 1 :
ds washout=183, baseline=183 :
prior_cvd 0 :
ds washout=365, baseline=183
0.01 0.02 0.03 0.04 0.05 0.06
: prior_cvd 1 :
ds washout=365, baseline=183
0.01 0.02 0.03 0.04 0.05 0.06
: prior_cvd 0 :
ds washout=365, baseline=365
2008_03_31 2008_06_30 2008_09_30 2008_12_31 2009_03_31 2009_06_30 2009_09_30
: prior_cvd 1 :
ds washout=365, baseline=365
●
Match new patients only Match all patients
eFigure 2. Hazard ratios of second generation sulfonylureas versus metformin with the 97.12% confidence intervals along surveillance time based on propensity−score−
matched data from 3 analysis datasets for caliper 0.25 SD of logit propensity score.
log hazard r atio
−2
−1 0 1 2
2008_03_31 2008_06_30 2008_09_30 2008_12_31 2009_03_31 2009_06_30 2009_09_30
:
PS Match new patients only :
ds washout=183, baseline=183
:
PS Match all patients :
ds washout=183, baseline=183 :
PS Match new patients only :
ds washout=365, baseline=183
−2
−1 0 1
: 2
PS Match all patients :
ds washout=365, baseline=183
−2
−1 0 1
2 PS Match new patients only : :
ds washout=365, baseline=365
2008_03_31 2008_06_30 2008_09_30 2008_12_31 2009_03_31 2009_06_30 2009_09_30
:
PS Match all patients :
ds washout=365, baseline=365
1
eTable 1. Standardized mean distances of baseline covariates on the full cohort and the matched data by exposure and method of matching with caliper 25% for the analysis dataset with washout and baseline both 365 days at the final analysis.
Variable
Full Cohort Match new patients only Match all patients
Metformin
Sulfonylurea 2
Standardized Difference
Metformi n
Sulfonylurea 2
Standardized Difference
Metformi n
Sulfonylurea 2
Standardize d Difference
N in Cohort (n = 18666) (n = 6574) (n = 5817) (n = 5817) (n = 5843) (n = 5843)
Age in years, mean(SD) 55.4(13.9) 66.8(12.8) 0.849 64.6(12.2) 65.1(12.5) 0.045 64.8(11.9) 65.1(12.4) 0.025
Male, % 42.9 51.8 0.178 51.6 51.3 0.006 51.0 51.1 0.001
Nursing Home Residence, % 0.0 0.0
ER visit prior 30 days, % 6.6 6.5 0.005 5.7 5.8 0.006 5.8 6.2 0.014
ER visit prior 31-365 days, % 22.5 26.1 0.084 23.1 23.6 0.013 23.2 23.8 0.013
Hospitalized prior 30 days, % 6.7 10.9 0.149 9.8 9.0 0.027 9.6 9.6 0.002
Hospitalized prior 31-365 days, % 25.2 36.3 0.242 33.0 32.5 0.012 33.0 32.8 0.004
Number OutPatient Visits, mean(SD) 6.9(9.6) 7.5(11.9) 0.053 6.6(10.1) 6.8(10.9) 0.024 6.7(10) 7(11.2) 0.023
Number Clinical Medications, mean(SD) 5.5(5.8) 4.6(5.8) 0.150 4.2(5.1) 4.6(5.8) 0.067 4.4(5.1) 4.6(5.8) 0.047
Asthma prior 30 days, % 0.3 0.3
Asthma prior 31-365 days, % 4.4 3.7 0.035 4.0 3.6 0.023 3.9 3.6 0.015
COPD prior 30 days, % 0.3 1.0
COPD prior 31-365 days, % 3.3 7.1 0.173 5.5 5.6 0.005 5.5 5.7 0.010
Cancer prior 30 days, % 0.6 1.0
Cancer prior 31-365 days, % 12.8 15.2 0.069 13.2 14.3 0.032 14.0 14.5 0.013
Dementia, % 0.8 2.5
Depression, % 7.0 5.5 0.064 5.0 5.3 0.014 5.1 5.3 0.010
Endstage renal disease, % 0.0 1.2
2
HIV/AIDS, % 0.1 0.1
History of fracture prior 30 days, % 0.1 0.2
History of fracture prior 31-365 days, % 1.6 2.9
Hyperlipidemia, % 37.7 40.2 0.051 37.4 39.8 0.048 38.6 39.3 0.013
Hypertension, % 40.3 48.8 0.172 45.4 46.6 0.026 46.2 46.5 0.007
Hypoglycemia prior 30 days, % 0.0 0.1
Hypoglycemia prior 31-365 days, % 1.1 0.7
Neuropathy, % 3.3 4.1 0.044 3.0 4.0 0.050 3.7 3.8 0.007
Obesity, % 10.0 6.0 0.148 5.1 6.0 0.039 5.7 5.9 0.010
Osteoporosis, % 2.3 3.6
Renal Insufficiency, % 0.4 5.0
Smoking, % 5.0 7.2 0.093 6.1 6.3 0.009 6.3 6.3 0.001
Ace Inhibitors, % 17.8 16.8 0.025 15.4 17.2 0.049 16.8 17.1 0.010
Alpha Block, % 2.8 4.1 0.071 4.0 3.9 0.004 3.8 4.0 0.011
Alpha G, % 0.1 0.2
Arbs, % 10.6 10.5 0.004 10.6 10.1 0.017 9.9 10.4 0.016
Beta Blocker, % 15.1 19.4 0.115 17.6 18.3 0.019 17.4 18.8 0.035
Calcium Channel Blocker, % 11.1 12.8 0.053 12.6 12.9 0.011 12.2 13.1 0.026
DDP 4, % 1.1 2.8
GLP 1, % 0.8 0.9
K spare, % 5.6 4.6 0.043 3.9 4.9 0.046 4.0 4.7 0.035
Lipid Mod, % 29.6 27.9 0.038 26.4 28.2 0.041 27.5 28.7 0.027
Loop Diuretics, % 4.4 9.1 0.186 7.0 7.2 0.011 7.3 7.2 0.003
Meglitinides, % 0.4 0.5
Symp Block, % 0.0 0.0
3
TZDS, % 4.2 8.1 0.163 6.1 7.4 0.051 6.7 7.1 0.014
Vaso, % 0.3 1.0
Prior CVD, % 14.9 29.2
Carotid prior 30 days, % 0.0 0.0
Carotid prior 31-365 days, % 0.0 0.0
Lower Amputation prior 30 days, % 0.0 0.0
Lower Amputation prior 31-365 days, % 0.0 0.0
Lower Revascularization prior 30 days, % 0.0 0.0 Lower Revascularization prior 31-365 days, % 0.0 0.0
Other Heart Disease prior 30 days, % 0.7 2.5
Other Heart Disease prior 31-365 days, % 8.9 19.6 0.311 15.5 15.6 0.003 15.4 15.9 0.015
Other Ischemic Heart Disease prior 30 days, % 0.6 1.9
Other Ischemic Heart Disease prior 31-365 days, % 8.1 16.7 0.266 13.9 14.0 0.003 14.3 14.0 0.009
Prior AMI prior 61-365 days, % 0.4 1.0
Stroke, broad prior 30 days, % 0.2 0.4
Stroke, broad prior 31-365 days, % 2.1 4.9
Stroke, narrow prior 30 days, % 0.1 0.2
Stroke, narrow prior 31-365 days, % 0.8 1.9
1
eTable 2. Sample sizes, pre- and post-matching of the full cohort and of the matched data by exposure and method of matching with caliper 25% for the analysis dataset with washout and baseline both 365 days at each analysis. Columns under “N_events” display the number of Acute MI events of the matched data by medication group.
Pre Matching Totals N events
quarter match_method Met Sul Total_matched Metformin Sulfonylureas Hazard Ratio 95% CI
2008_03_31 Match ALL 5428 1114 2058 4 2 0.48 0.09 2.64
2008_03_31 Match New Only 5428 1114 2058 4 2 0.48 0.09 2.64
2008_06_30 Match ALL 6057 1270 2346 4 4 0.99 0.24 4.05
2008_06_30 Match New Only 6057 1270 2358 4 3 0.77 0.17 3.45
2008_09_30 Match ALL 11232 4145 7356 5 4 0.86 0.23 3.24
2008_09_30 Match New Only 11232 4145 7288 6 5 0.90 0.27 2.97
2008_12_31 Match ALL 14407 5566 9824 12 16 1.43 0.68 3.04
2008_12_31 Match New Only 14407 5566 9754 14 17 1.26 0.62 2.57
2009_03_31 Match ALL 16214 6042 10728 17 21 1.33 0.70 2.53
2009_03_31 Match New Only 16214 6042 10664 19 22 1.21 0.66 2.25
2009_06_30 Match ALL 17667 6357 11304 16 28 1.84 0.99 3.41
2009_06_30 Match New Only 17667 6357 11242 21 27 1.33 0.75 2.36
2009_09_30 Match ALL 18666 6574 11686 16 28 1.92 1.04 3.55
2009_09_30 Match New Only 18666 6574 11634 21 31 1.56 0.90 2.72