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1 Supplementary Online Content Jørgensen ME, Hlatky MA, Køber L, et al. β-blocker associated risks in patients with uncomplicated hypertension undergoing noncardiac surgery. JAMA Intern Med. Published online October 5, 205. doi:0.00/jamainternmed etable. Variable coding and definitions etable 2. Use of beta blocker subtypes in the study population etable 3. Distribution of type of surgery stratified by beta blocker use etable 4. Distribution of key variables in patients with and without missing values efigure. Secondary outcomes (individual MACE components) by antihypertensive drug regimen efigure 2. Risks of MACE and mortality including patients treated with metoprolol or atenolol only efigure 3. Patients with a diagnosis of hypertension and one-drug antihypertensive treatment efigure 4. Main results adjusted for type of surgery in 7 categories efigure 5. Risks associated with each study drug efigure 6. Main results adjusted for alcohol and smoking with imputation for missing values efigure 7. Analyses including patients on a 4-drug antihypertensive regimen efigure 8. Estimates for other variables from the main model This supplementary material has been provided by the authors to give readers additional information about their work. Table of Contents etable Variable coding and definitions*... 3 etable 2 Use of beta blocker subtypes in the study population.... 5

2 etable 3 Distribution of type of surgery stratified by beta blocker use etable 4 Distribution of key variables in patients with and without missing values efigure Secondary outcomes (individual MACE components) by antihypertensive drug regimen efigure 2 Risks of MACE and mortality including patients treated with metoprolol or atenolol only efigure 3 Patients with a diagnosis of hypertension and one drug antihypertensive treatment efigure 4 Main results adjusted for type of surgery in 7 categories.... efigure 5 Risks associated with each study drug efigure 6 Main results adjusted for alcohol and smoking with imputation for missing values efigure 7 Analyses including patients on a 4 drug antihypertensive regimen efigure 8 Estimates for other variables from the main model.... 5

3 etable Variable coding and definitions* Variable Coding and definitions Pharmacotherapy ATC code Beta blockers C07 RAS inhibitors C09 Calcium antagonists C08 Thiazides C03A Aldosterone antagonists C03D Digoxin C0AA Vitamin K anatagonists B0AA Lipid lowering therapy C0A Clopidogrel B0AC04 Glucose lowering agents A0 Loop diuretics C03CA0 RAS inhibitors and calcium antagonist combination C09DX0, C09DB0 therapy a RAS inhibitors and thiazides C09DA, C09BA combination therapy a Beta blockers and thiazides C07B combination therapy a Comorbidity ICD 0 code Ischemic stroke I63, I64 Acute myocardial infarction I2 Chronic obstructive pulmonary disease J42, J44 Anemia D60 D69 Cancer C00 C97 Renal disease N03, N04, N7, N8, N9, R34, I2, I3 Rheumatologic disease M05, M06, M32, M33, M34, M353 Peripheral artery disease I70, I74 Liver disease K70 K77, B50, B60, B90 Diabetes b E0 E4 (without E09, E9, E29, E39) Chronic heart failure c I42, I50, I0, J89 Ischemic heart disease I20, I23, I24, I25, Atrial fibrillation I48 Surgery category NCSP code Ear/nose/throat KD Minor orthopedic KNC, KND, KNH Major orthopedic KN (except KNC, KND, KNH) Abdominal (bowel) KJC, KJC, KJF, KJG, KJH Abdominal (non bowel) KJ (except KJC, KJF, KJG, KJH) Breast KH Plastic KQ Endocrine KB Eye KC Female reproductive KL Male reproductive KKD, KKE, KKF, KKG Intracranial KAA Neurological KA (Except KAA) Non arterial vessels KPH, KPJ Arterial vessels KP (except KPH, KPJ)

4 Thoracic/pulmonary KG Urology KK (except KKD, KKE, KKF, KKG) Surgery risk Surgery subtypes Low risk Breast, plastic, endocrine, and eye Elevated risk Ear/nose/throat, major orthopedic, minor orthopedic, abdominal, female reproductive, male reproductive, intracranial, neurological, non arterial vessels, thoracic/pulmonary, urology and arterial vessel surgery (exceptions: endoscopic orthopedic procedures and peripheral nerve surgery were low risk) *Footnote: a Treatment with a combination drug translated into treatment with two individual antihypertensive drugs. b Diabetes defined as present diagnosis or from use of glucose lowering agents. c Chronic heart failure defined as present diagnosis or from use of loop diuretics. ATC code, Anatomical Therapeutic Classification System. ICD 0 code, International Classification of Disease 0 th edition. NCSP code, NOMESCO s Classification of Surgical Procedures (Danish version).

5 etable 2 Use of beta blocker subtypes in the study population. Beta blocker subtypes main cohort. Patients, n (%) Proportion of beta blocker treated patients, % No beta blocker 40,676 (73.5) NA Atenolol 2,422 (4.4) 6.5 Bisoprolol 707 (.3) 4.8 Carvedilol 974 (.8) 6.7 Metoprolol 9,302 (6.8) 63.5 Nebivolol 62 (0.) 0.4 Pindolol 8 (0.2) 0.8 Propranolol 954(.7) 6.5 Labetalol 05 (0.2) 0.7 Total 55,320 ( 00) 00

6 etable 3 Distribution of type of surgery stratified by beta blocker use. Type of surgery n(%) With beta blockers n=4,644 Without beta blockers n=40,676 Type of surgery n(%) With beta blockers n=4,644 Without beta blockers n=40,676 Ear/nose/throat 93 (.3) 540 (.3) Male reproductive 38 (0.9) 503 (.2) Minor orthopedic,47 (0.0) 4,027 (9.9) Intracranial 9 (.3) 479 (.2) Major orthopedic 5,069 (34.6) 5,38 (37.2) Neurological 670 (4.6),870 (4.6) Abdominal (bowel) 636 (4.3),635 (4.0) Non arterial vessels 577 (3.9),38 (3.4) Breast 293 (2.0) 695 (.7) Arterial vessels 244 (.7) 56 (.4) Plastic 768 (5.2),905 (4.7) Thoracic/pulmonary 46 (.0) 43 (.0) Endocrine 43 (.0) 34 (0.8) Urology 930 (6.4) 2,54 (6.2) Abdominal (nonbowel),736 (.9) 5,06 (2.3) Female reproductive Eye 320 (2.2) 97 (2.3),9 (7.6) 2,74 (6.7)

7 etable 4 Distribution of key variables in patients with and without missing values. No missing in alcohol Missing in alcohol No missing in smoking Missing in smoking Age (Mean, years) Gender (% female) Beta blocker (% treated) Urgency (% acute) Surgery risk (% elevated)

8 efigure Secondary outcomes (individual MACE components) by antihypertensive drug regimen. A - 30-day Cardiovascular Death 3.50 ( ) 2.76 ( ) 2.25 ( ).23 ( ).29 ( ) 0.82 (4-.25).04 ( ) 87/ / /878 32/ / / / /4628 B - 30-day Non-fatal stroke 2 ( ).69 ( ) 0.75 ( ).32 ( ).9 ( ) 0.83 ( ).44 ( ) 40/ /2789 7/878 5/3427 9/6550 5/6055 7/9248 5/4628 C - 30-day non-fatal AMI 0.96 ( ).24 ( ) 0.77 ( ).07 (5-2.07) 0.67 ( ).46 ( ) 3 ( ) 34/ /2789 4/878 4/3427 5/6550 7/ /9248 5/4628

9 efigure 2 Risks of MACE and mortality including patients treated with metoprolol or atenolol only. Only atenolol 30-day MACE.2 ( ) 4.3 ( ).98 ( ) 0.62 ( ).4 ( ) 0.98 ( ).0 ( ) 6/20,745 4/43 2/354 0/672 5/965 55/6,055 77/9,248 49/4, day all-cause mortality Only metoprolol 2,34,25 4,37 2,60,45 4,68 2,37,4,95,36 0,8 2,29,6 0,90,49 0,82 0,64,05,2 0,94,56 256/20,745 /43 3/354 7/672 6/965 93/6,055 95/9,248 94/4, day MACE 2.69 ( ).73 ( ).25 ( ).24 ( ).3 ( ) 0.97 ( ).0 ( ) 6/20,745 36/,757 8/,26 2/2,04 49/4,35 55/6,055 77/9,248 49/4, day all-cause mortality.92 ( ).34 ( ).9 ( ).20 ( ).5 ( ) 0.82 ( ).22 ( ) 256/ /757 22/26 35/204 66/435 93/ / /4628

10 efigure 3 Patients with a diagnosis of hypertension and one drug antihypertensive treatment. Risks of 30-day MACE A - Main cohort, patients with hypertension diagnosis only ( ) 3.46 ( ).7 (4-2.56).69 ( ).60 ( ).2 ( ).8 ( ) 38/64 7/057 6/682 8/04 30/ /20 25/3523 4/448 B - Hypertension diagnosis and one-drug treatment Thiazides only Calcium antagonists only Beta blockers only RAS-inhibitors only.9 ( ) 0.72 ( ).67 ( ). ( ) 2.46 ( ) 3.48 ( ).5 (3-2.50).7 ( ).60 ( ).3 ( ).6 ( ) 23/2,53 8/2,970 20/,845 37/5,436 38/6,4 7/,057 6/682 8/,04 30/2,648 22/2,0 25/3,523 4/,448

11 efigure 4 Main results adjusted for type of surgery in 7 categories. Additional adjustment for type of surgery. A - 30-day MACE 2.08 ( ) 2.0 ( ).57 ( ).5 ( ).0 ( ) 0.97 ( ).04 ( ) 6/20,745 46/2,789 35/,878 4/3,427 7/6,550 55/6,055 77/9,248 49/4,628 B - 30-day all-cause mortality.67 ( ).7 (.2-2.4).65 ( ).23 ( ).4 ( ) 0.83 ( ).27 ( ) 256/20,745 58/2,789 44/,878 73/3,427 07/6,550 93/6,055 95/9,248 94/4,628 Legend: No interaction were found between beta blocker therapy and type of surgery for the risk of MACE, P=0.262.

12 efigure 5 Risks associated with each study drug. A - 30-day MACE RAS-inhibitors Beta blockers Calcium antagonists Thiazides 0.83 ( ).29 (.0-.65) 0.87 ( ) 0.67 (2-0.87) 396/44,302 93/4, /24,54 38/43,338 B - 30-day all-cause mortality RAS-inhibitors Beta blockers Calcium antagonists Thiazides 0.73 (9-0.90).20 ( ) 0.83 ( ) 0.73 (9-0.9) 586/44, /4, /24,54 60/43,338

13 efigure 6 Main results adjusted for alcohol and smoking with imputation for missing values. A - 30-day MACE 2.0 ( ).96 ( ).4 ( ).2 (0.9-.6).06 ( ) 0.96 ( ).00 ( ) 6/20,745 46/2,789 35/,878 4/3,427 7/6,550 55/6,055 77/9,248 49/4,628 B - 30-day all-cause mortality.62 (.2-2.8).48 ( ).53 ( ).22 ( ).3 ( ) 0.78 ( ).6 ( ) 256/20,745 58/2,789 44/,878 73/3,427 07/6,550 93/6,055 95/9,248 94/4,628

14 efigure 7 Analyses including patients on a 4 drug antihypertensive regimen. 30-day MACE Beta blocker + 3 others 2.7 ( ) 2.7 ( ).57 ( ).23 ( ).79 ( ).2 ( ) 0.97 ( ).03 ( ) 6/20,745 46/2,789 35/,878 4/3,427 7/6,550 43/2,825 55/6,055 77/9,248 49/4, day all-cause mortality Beta blocker + 3 others.8 ( ).69 ( ).65 ( ).32 ( ).46 ( ).6 ( ) 0.82 ( ).24 ( ) 256/20,745 58/2,789 44/,878 73/3,427 07/6,550 5/2,825 93/6,055 95/9,248 94/4,628

15 efigure 8 Estimates for other variables from the main model. 30-day MACE Diabetes Venous thromboembolisms Rheumatologic disease Cancer Anemia Chronic obstructive pulmonary disease Acetylsalicylic acid Lipid lowering therapy Surgery risk - low vs. elevated Calendar year Body mass index Gender - female vs. male Age.00. (ref) 2.6 ( ) 2.7 ( ).56 ( ).22 ( ).2 ( ) 0.97 ( ).02 ( ).29 ( ) 2.66 ( ) 2. ( ).0 ( ).0 ( ).84 ( ).32 ( ) 0.93 ( ) 0.80 (9-.09) 0.92 ( ) 0.96 ( ) 0.69 (7-0.83) 0.97 ( )