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1 Supplementary material Comparison of propensity score methods and covariate adjustment a practical evaluation in four cardiovascular studies Table of Contents Supplementary tables Table S1: Results from paired and unpaired analyses following propensity score matching Table S2: Propensity score model for CHARM Table S3: Propensity score model for ADAPT-DES Table S4: Propensity score model for THIN Table S5: Propensity score model for PROMETHEUS Table S6: Covariate adjustment for CHARM Table S7: Covariate adjustment for ADAPT-DES Table S8: Covariate adjustment for THIN Table S9: Covariate adjustment for PROMETHEUS Table S10: Events per stratum in ADAPT-DES Supplementary figures Figure S1: CHARM results with and without trimming Figure S2: ADAPT-DES results with and without trimming Figure S3: THIN results with and without trimming Figure S4: PROMETHEUS results with and without trimming
2 Matched, N(%) Control Treated Hazard ratio (95% CI) from unpaired analysis Unmatched, N(%) Matched, N(%) Unmatched, N(%) Hazard ratio from paired analysis CHARM 3238 (95.3%) 158 (4.7%) 3238 (77.0%) 965 (23.0%) 0.71 (0.65 to 0.79) 0.72 (0.65 to 0.79) ADAPT-DES 3289 (66.7%) 1641 (33.3%) 3289 (90.1%) 361 (9.9%) 2.07 (1.12 to 3.84) 2.12 (1.14 to 3.93) THIN 3899 (25.0%) (75.0%) 3899 (97.1%) 118 (2.9%) 0.84 (0.80 to 0.89) 0.84 (0.80 to 0.89) PROMETHEUS (35.2%) (64.8%) (69.6%) 9354 (30.4%) 0.85 (0.71 to 1.02) 0.85 (0.70 to 1.02) Supplementary table S1: Results from paired and unpaired analyses following propensity score matching Results from paired analyses were calculated by fitting a Cox-proportional hazards model which included a frailty term specific to each matched pair. Results from unpaired analysis used the same matched pairs data but ignored matching in the analysis.
3 Variable Effect SE p (Intercept) < Candesartan NYHA classification Age < Ejection Fraction (per 5% decrease below 45) Current Smoker Diabetes Mellitus Dependent oedema Mitral regurgitation Previous myocardial infarction < Previous atrial fibrillation Diabetes: Insulin Treated Oral therapy Treated Diabetes Mellitus CHF time: <6 months Diagnosis of CHF over 2 years ago Cardiomegaly Pulmonary crackles < Sex: Female BMI Supplementary table S2. Propensity score model for CHARM.
4 Variable Log odds ratio SE p (Intercept) < Diabetes Mellitus Insulin for Diabetes Mellitus Medications: ACE Medications: ARB Medications: STATIN Medications: NIACIN Medications: FIBRICACID Medications: BETABLOCKER Medications: CALCIUMBLOCKER Medications: COUMADIN Medications: INSULIN Medications: ORALHYPOGLYCEM Medications: NSAID Medications: COX2INHIBITOR Medications: DIGOXIN Medications: OANTIHYPERTENS Medications: IVPRESSOR Medications: CILOSTAZOL Medications: AMIODARONE Medications: ATROPINE Medications: PPINHIBITORS < Medications: DIURETIC Medications: RETAVASE Medications: TPA Medications: TNK Medications: OTHER Ever smoked INHOSP_TIMI_MAJOR Patient race: Asian Pacific Patient race: Caucasian Patient race: Hispanic Patient race: Multi Racial Patient race: Native American Patient race: Other Patient race: Unknown Dialysis Renal insufficiency BMI < Age < Supplementary table S3. Propensity score model for ADAPT-DES
5 Variable Log odds ratio SE p (Intercept) BMI category < BMI category > < BMI category missing < Age < Sex < Alcohol status: ex-drinker Alcohol status: current drinker unknown < Alcohol status: rare drinker <2u/d < Alcohol status: moderate drinker 3-6u/d < Alcohol status: excessive drinker >6u/d < Alcohol status: drinking status unknown < Smoking status: ex Smoking status: current Smoking status: unknown Diabetes < Atrial fibrillation < Heart failure HRT (within 1 year) Thyroid disease Oral steroid (within 6 months) Inhaled steroid (within 6 months) Antipsychotics (within 6 months) Antidepressants (within 6 months) Townsend < Drug prescriptions rate < Renal disease (within 6 months) Fibrates (within 3 months) < Nonstatin/fibrate lipid lowerers Consultations rate < Hyperlipidaemia < Hypertension < Aspirin < Coronary heart disease < Cerebrovascular disease Peripheral vascular disease Beta-blocker < Nitrates < Cytochrome Hepatic disease (within 6 months) < Anticoagulants Ca ++ blocker/k + activator < Other cardiovascular drugs < Cancer < Diuretics Other circulatory disease < Dementia < Other atheroma Antihypertensives < Supplementary table S4. Propensity score model for THIN
6 Variable Effect SE p (Intercept) < CAD Presentation: Non-ST-elevation myocardial infarction CAD Presentation: ST-elevation myocardial infarction Diabetes mellitus, no insulin Diabetes mellitus, insulin Age < Age squared < Procedural Bivalirudin Smoker < Sex: Female Black/African American Hypertension Family history of CAD Prior PAD Prior CHF Total stent length: Total stent length: < Stent diameter < Hypercholesterolemia Previous MI egfr using CKD-EPI Stent type: 1st generation Stent type: Bare-metal stent < BMI decile Hemoglobin Centre: Utah Centre: Aurora Centre: Pittsburgh < Centre: Duke < Centre: Cliveland < Centre: Christiana < Centre: Mount Sinai < Glycoprotein IIb/IIIa Prior Cerebrovascular Disease < Previous PCI < Previous CABG < Supplementary table S5. Propensity score model for PROMETHEUS
7 Variable Effect Hazard ratio SE p Treatment effect (beta-blockers) < Candesartan NYHA classification < Age < Ejection Fraction (per 5% decrease below 45) < Current Smoker Diabetes Mellitus Dependent oedema Mitral regurgitation Previous myocardial infarction Previous atrial fibrillation Diabetes: Insulin Treated Oral therapy Treated Diabetes Mellitus CHF time: <6 months Diagnosis of CHF over 2 years ago Cardiomegaly < Pulmonary crackles Sex: Female BMI < Supplementary table S6. Covariate adjustment for CHARM
8 Variable Effect Hazard ratio SE p Treatment effect Age Sex: male Diabetes Mellitus Insulin for Diabetes Mellitus Medications: ACE Medications: ARB Medications: STATIN Medications: NIACIN Medications: FIBRICACID < < Medications: BETABLOCKER Medications: CALCIUMBLOCKER Medications: COUMADIN Medications: INSULIN Medications: ORALHYPOGLYCEM Medications: NSAID Medications: COX2INHIBITOR < < Medications: DIGOXIN Medications: OANTIHYPERTENS Medications: IVPRESSOR Medications: CILOSTAZOL < < Medications: AMIODARONE Medications: ATROPINE < < Medications: PPINHIBITORS Medications: DIURETIC Medications: RETAVASE < < Medications: TPA < < Medications: TNK < < Medications: OTHER Ever smoked INHOSP_TIMI_MAJOR < < Patient race: Asian Pacific < < Patient race: Caucasian Patient race: Hispanic < < Patient race: Multi Racial < < Patient race: Native American < < Patient race: Other < < Patient race: Unknown Dialysis Renal insufficiency BMI Supplementary table S7. Covariate adjustment for ADAPT-DES
9 Variable Effect Hazard ratio SE p Treatment effect < Age < Sex < BMI category < BMI category > < BMI category missing Alcohol status: ex-drinker Alcohol status: current drinker unknown Alcohol status: rare drinker <2u/d < Alcohol status: moderate drinker 3-6u/d Alcohol status: excessive drinker >6u/d Alcohol status: drinking status unknown < Smoking status: ex < Smoking status: current Smoking status: unknown < Diabetes < Atrial fibrillation Heart failure < HRT (within 1 year) < Thyroid disease Oral steroid (within 6 months) < Inhaled steroid (within 6 months) < Antipsychotics (within 6 months) < Antidepressants (within 6 months) Townsend < Drug prescriptions rate < Renal disease (within 6 months) < Fibrates (within 3 months) Nonstatin/fibrate lipid lowerers Consultations rate Hyperlipidaemia Hypertension Aspirin Coronary heart disease < Cerebrovascular disease < Peripheral vascular disease < Beta-blocker < Nitrates Cytochrome Hepatic disease (within 6 months) < Anticoagulants Ca ++ blocker/k + activator Other cardiovascular drugs Cancer < Diuretics < Other circulatory disease Dementia < Other atheroma Antihypertensives Supplementary table S8. Covariate adjustment for THIN
10 Variable Effect Hazard ratio SE p Treatment effect CAD Presentation: Non-ST-elevation myocardial infarction CAD Presentation: ST-elevation myocardial infarction Diabetes mellitus, no insulin Diabetes mellitus, insulin Age Age squared Procedural Bivalirudin Smoker Sex: Female Black/African American Hypertension Family history of CAD Prior PAD Prior CHF Total stent length: Total stent length: < Stent diameter Hypercholesterolemia Previous MI egfr using CKD-EPI Stent type: 1st generation Stent type: Bare-metal stent < BMI decile Hemoglobin Centre: Utah Centre: Aurora Centre: Pittsburgh Centre: Duke < Centre: Cliveland < Centre: Christiana Centre: Mount Sinai Glycoprotein IIb/IIIa Prior Cerebrovascular Disease Previous PCI Previous CABG Supplementary table S9. Covariate adjustment for PROMETHEUS
11 Stratum PS boundaries Number of individuals Number of events % events out of total % % % % % % % % % % Supplementary table S10. Propensity score stratification for the ADAPT-DES study with 10 strata. Only a small percentage of individuals in each stratum experiences an event resulting in as little as 1 event in some strata
12 Supplementary figure S10. Comparison of the results for the CHARM study with no trimming (top), 1% trimming (middle) and 5% trimming (bottom)
13 Supplementary figure S11. Comparison of the results for the ADAPT-DES study with no trimming (top), 1% trimming (middle) and 5% trimming (bottom)
14 Supplementary figure S12. Comparison of the results for the THIN study with no trimming (top), 1% trimming (middle) and 5% trimming (bottom)
15 Supplementary figure S13. Comparison of the results for the PROMETHEUS study with no trimming (top), 1% trimming (middle) and 5% trimming (bottom)
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