Supplementary Materials
Use of Cardioselective β-blockers and Overall Death and Cardiovascular Outcomes in Patients with COPD:
a Population-based Cohort Study
Authors Yaa-Hui Dong, PhD; Chia-Hsuin Chang, MD, ScD*; Li-Chiu Wu, MS; Mei-Shu Lai, MD, PhD
*Correspondence to
Dr. Chia-Hsuin Chang ()
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Appendix Table 1 Anatomical Therapeutic Chemical (ATC) classification system codes used to identify initiators of cardioselective BBs or non-dihydropyridine CCBs
Medication / ATC Classification System CodesCardioselective BBs
Practolol / C07AB01
Metoprolol / C07AB02
Atenolol / C07AB03
Acebutolol / C07AB04
Betaxolol / C07AB05
Bevantolol / C07AB06
Bisoprolol / C07AB07
Celiprolol / C07AB08
Epanolol / C07AB10
s-Atenolol / C07AB11
Nebivolol / C07AB12
Talinolol / C07AB13
Metoprolol, combinations / C07AB52
Bisoprolol, combinations / C07AB57
Metoprolol and thiazides / C07BB02
Atenolol and thiazides / C07BB03
Acebutolol and thiazides / C07BB04
Bevantolol and thiazides / C07BB06
Bisoprolol and thiazides / C07BB07
Nebivolol and thiazides / C07BB12
Metoprolol and thiazides, combinations / C07BB52
Metoprolol and other diuretics / C07CB02
Atenolol and other diuretics / C07CB03
Atenolol and other diuretics, combinations / C07CB53
Atenolol, thiazides and other diuretics / C07DB01
Metoprolol and other antihypertensives / C07FB02
Atenolol and other antihypertensives / C07FB03
Bisoprolol and other antihypertensives / C07FB07
Non-dihydropyridine CCBs
Verapamil / C08DA01
Verapamil, combinations / C08DA51
Diltiazem / C08DB01
BBs=β blockers, CCBs=calcium channel blockers.
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Appendix Table 2 International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnostic codes used to identify baseline comorbidities for initiators of cardioselective BBs or non-dihydropyridine CCBs
Comorbidities / ICD-9-CM CodesHypertension* / 401-404
Ischemic heart disease* / 411, 413, 414
Myocardial infarction* / 410, 412
Coronary revascularization*,† / 68023A,68023B, 68024A,68024B,68025A, 68025B,83064A1, 97901K, 97902A, 97903B, 97906K, 97907A, 97908B, 97911K, 97912A, 97913B,97916K, 97917A, 97918B, 33076A, 33076B, 33077A, 33077B, 33078A, 33078B, 97511K, 97512A, 97513B, 97516K, 97517A, 97518B, 97521K, 97522A, 97523B
Cardiac dysrhythmia* / 427
Atrial fibrillation* / 427.3
Congestive heart failure* / 428, 398.91, 402.01, 402.11, 402.91, 404.01, 404.11, 404.91, 404.03, 404.13, 404.93
Cereborvascular disease* / 430-438
Ischemic stroke* / 433, 434, 436 except 800-804, 850-854, V57
Hemorrhagic stroke* / 430-432
Peripheral vascular disease* / 440.2, 440.4, 443.81, 443.9
Hyperlipidemia / 272
Diabetes mellitus / 250
Thyroid disease / 244.9
Asthma§ / 493
Pneumonia, influenza, and acute bronchitis§ / 480-487, 466
Chronic liver disease / 070.2, 070.3, 070.41, 070.44, 070.51, 070.54, V02.61, V02.62, 571.0, 571.1, 571.2, 571.3, 571.4, 571.5, 571.6
Gastritis or peptic ulcer disease / 531-535,578.0, 578.1,578.9
Chronic kidney disease / 403.01, 403.11, 403.91, 404.02, 404.03, 404.12, 404.13, 404.92, 404.93, 585 ,V45.1,
V56.0, V56.8
Rheumatoid arthritis / Osteoarthritis / 710,714, 715, 720
Osteoporosis / 733.0
Gout / 274
Any cancer other than lung cancer / 140-161, 163-208
Lung cancer / 162
Dementia / 290.0-290.4,291.2,294.1,331.0-331.2,
290.10-290.13,290.20,290.21,290.40-290.43,294.10,294.11,331.11,331.19,331.82
Seizure / 345, 780.3
Depressive disorder / 296.2,296.3,298.0,300.4,309.0,309.1, 293.83,296.90,309.28,296.82, 311
Anxiety disorder / 300.0-300.3,300.5-300.9
Psychotic disorder / 295, 297-299, 290.8, 290.9, 780.1
Bipolar disorder / 296.0, 296.1, 296.4-296.9
BBs=β blockers, CCBs=calcium channel blockers.
*Cardiovascular episodes included hypertension, ischemic heart disease, myocardial infarction, coronary revascularization, cardiac dysrhythmia, atrial fibrillation, congestive heart failure, cerebrovascular disease, ischemic stroke, hemorrhagic stroke, and peripheral vascular disease.
†Based on National health insurance service claims codes (http://www.nhi.gov.tw/query/query2.aspx?menu=20&menu_id=710&webdata_id=3633&WD_ID=900 accessed October, 2013).
§Respiratory -related episodes included chronic obstructive pulmonary disease, asthma, pneumonia, influenza, and acute bronchitis.
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Appendix Table 3 Anatomical Therapeutic Chemical (ATC) classification system codes used to identify baseline medication use for initiators of cardioselective BBs or non-dihydropyridine CCBs
Medication / ATC Classification System CodesACEIs / ARAs / C09
Non-carioselective beta blockers / C07AA, C07AG, C07BA, C07BG, C07CA, C07CG,
C07DA, C07EA, C07FA
Dihydropyridine calcium channel blockers / C08C, C08E, C08G
Diuretics / C03, C07B, C07C, C07D, C08G
Other anti-hypertensive agents / C02
Nitrates / C01DA
Anti-arrhythmic agents / C01B
Digoxin / C01AA
Aspirin / B01AC06, N02BA01
Clopidogrel / B01AC04
Warfarin / B01AA03
Statins / Fibrates / C10AA, C10AB
Insulin / A10A
Oral anti-diabetic agents / A10B
Thyroid-therapy drugs / H03
SABA / R03AC02, R03AC03, R03AC04, R03AC06, R03AK03, R03AK04
SAMA / R03BB01
LABA / R03AC12, R03AC13, R03AC16, R03AC18, R03AK06, R03AK07
LAMA / R03BB04
ICS / R03BA, R03AK06, R03AK07
Oral beta-2 agonists / R03CC02, R03CC03, R03CC04, R03CC05, R03CC08, R03CC09, R03CC12, R03CC13, R03CC91
Oral xanthines / R03DA04, R03DA05
Oral corticosteroids / H02AB, H02BX
Antibiotics / J01
Histamine 2 antagonists / PPIs / A02BA, A02BC
COX-2 selective NSAIDs / M01AH
COX-2 nonselective NSAIDs / M01AA, M01AB, M01AC, M01AE, M01AG, M01AX
Anti-epileptics / N03
Anti-depressants / N06A
Anxiolytics / N05B
Hypnotics / N05C
Anti-psychotics / N05A
Estrogen / G03C
Uric acid lowering agents / M04A
ACEIs=angiotensin converting enzyme inhibitors, ARAs=angiotensin Ⅱ receptor antagonists, BBs=β blockers, CCBs=calcium channel blockers, Cox=cyclooxygenase, ICS= inhaled corticosteroids, LABA=long-acting beta-2 agonists, LAMA=long-acting muscarinic antagonist, NSAIDs=non-steroidal anti-inflammatory drugs, PPIs=proton pump inhibitors, SABA=short-acting beta-2 agonists, SAMA=short-acting muscarinic antagonists.
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Appendix Table 4 Subgroup analyses for risk of overall death* comparing use of cardioselective BBs versus use of non-dihydropyridine CCBs
Subgroup / Number of patients / HR (95% CI)Age >= 65 years / 78,284 / 0.82 (0.78-0.85)
Age < 65 years / 29,618 / 0.88 (0.77-0.99)
Men / 65,729 / 0.84 (0.80-0.88)
Women / 42,173 / 0.85 (0.80-0.91)
With hypertension / 81,188 / 0.82 (0.79-0.86)
Without hypertension / 26,714 / 0.87 (0.79-0.95)
With myocardial / 3,427 / 0.91 (0.78-1.07)
Without myocardial / 104,475 / 0.84 (0.81-0.87)
With heart failure / 23,975 / 0.89 (0.84-0.94)
Without heart failure / 83,927 / 0.82 (0.78-0.86)
BBs=β blockers, CCBs=calcium channel blockers.
*Based on the propensity score matching approach
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Appendix Figure 1 Flowchart of the study cohort assembly
COPD patients* during Jan 1 2007 - December 31 2011 (N = 582,310)Excluded due to:
l Patients without any prescription of cardioselective BBs or non-dihydropyridine CCBs (N = 374,851)
COPD patients with any prescription of cardioselective BBs or non-dihydropyridine CCBs during Jan 1 2007 - December 31 2011 (N = 207,459)
Excluded due to:
l Patients with undetermined gender (N = 138)
l Patients with age more than 100 years or undetermined on the index date (N = 39)
l Patients who did not have continuous insurance coverage within 1 year before the index date (N = 61)
l Patients simultaneously received cardioselective BBs and non-dihydropyridine CCBs on the index date (N = 2,411)
Potential study participants (N = 204,810)
Excluded due to:
l Patients with any prescription of BBs or non-dihydropyridine CCBs within 1 year before the index date (N = 96,865)
l Patients with outcomes of interest on the index date (N = 43)
Patients included in the analysis
(N = 107,902)
BBs=β blockers, CCBs=calcium channel blockers, COPD=chronic obstructive pulmonary disease.
*Patients should have one COPD diagnosis, be aged 45 years or older, and receive bronchodilator therapy on two separate dates.
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