1 SUPPLEMENTAL DIGITAL CONTENT
TABLE S1. Incidences of cardiovascular events Myocardial
infarction [1] Angina[2] Stroke[3] Heart failure [4]
Age
(years) Men Women Men Women Men Women Men Women 30 0.00024 0.00001 0.00016 0.00012 0.00006 0.00002 0 0.00004 31 0.00024 0.00001 0.00022 0.00013 0.00006 0.00002 0 0.00004 32 0.00024 0.00001 0.00027 0.00013 0.00006 0.00002 0 0.00004 33 0.00024 0.00001 0.00032 0.00010 0.00006 0.00002 0 0.00004 34 0.00024 0.00001 0.00037 0.00015 0.00006 0.00002 0 0.00004 35 0.00044 0.00005 0.00042 0.00015 0.00014 0.00029 0.00020 0.00020 36 0.00044 0.00005 0.00048 0.00016 0.00014 0.00029 0.00020 0.00020 37 0.00044 0.00005 0.00053 0.00017 0.00014 0.00029 0.00020 0.00020 38 0.00044 0.00005 0.00058 0.00018 0.00014 0.00029 0.00020 0.00020 39 0.00044 0.00005 0.00063 0.00018 0.00014 0.00029 0.00020 0.00020 40 0.00121 0.00023 0.00068 0.00019 0.00014 0.00029 0.00020 0.00020 41 0.00121 0.00023 0.00083 0.00029 0.00014 0.00029 0.00020 0.00020 42 0.00121 0.00023 0.00099 0.00039 0.00014 0.00029 0.00020 0.00020 43 0.00121 0.00023 0.00113 0.00049 0.00014 0.00029 0.00020 0.00020 44 0.00121 0.00023 0.00127 0.00059 0.00014 0.00029 0.00020 0.00020 45 0.00202 0.00040 0.00142 0.00069 0.00128 0.00081 0.00030 0.00010 46 0.00202 0.00040 0.00157 0.00080 0.00128 0.00081 0.00030 0.00010 47 0.00202 0.00040 0.00172 0.00090 0.00128 0.00081 0.00030 0.00010 48 0.00202 0.00040 0.00186 0.00100 0.00128 0.00081 0.00030 0.00010 49 0.00202 0.00040 0.00201 0.00110 0.00128 0.00081 0.00030 0.00010 50 0.00392 0.00095 0.00216 0.00120 0.00128 0.00081 0.00030 0.00010 51 0.00392 0.00095 0.00255 0.00146 0.00128 0.00081 0.00030 0.00010 52 0.00392 0.00095 0.00294 0.00171 0.00128 0.00081 0.00030 0.00010 53 0.00392 0.00095 0.00333 0.00197 0.00128 0.00081 0.00030 0.00010 54 0.00392 0.00095 0.00372 0.00223 0.00128 0.00081 0.00030 0.00010 55 0.00528 0.00143 0.00411 0.00248 0.00188 0.00203 0.00170 0.00070 56 0.00528 0.00143 0.00450 0.00274 0.00188 0.00203 0.00170 0.00070 57 0.00528 0.00143 0.00489 0.00300 0.00188 0.00203 0.00170 0.00070 58 0.00528 0.00143 0.00528 0.00326 0.00188 0.00203 0.00170 0.00070 59 0.00528 0.00143 0.00567 0.00351 0.00188 0.00203 0.00170 0.00070 60 0.00741 0.00201 0.00606 0.00377 0.00188 0.00203 0.00170 0.00070 61 0.00741 0.00201 0.00629 0.00417 0.00188 0.00203 0.00170 0.00070 62 0.00741 0.00201 0.00651 0.00456 0.00188 0.00203 0.00170 0.00070 63 0.00741 0.00201 0.00673 0.00495 0.00188 0.00203 0.00170 0.00070 64 0.00741 0.00201 0.00696 0.00535 0.00188 0.00203 0.00170 0.00070 65 0.00987 0.00350 0.00718 0.00574 0.00610 0.00437 0.00390 0.00230 66 0.00987 0.00350 0.00740 0.00614 0.00610 0.00437 0.00390 0.00230 67 0.00987 0.00350 0.00763 0.00653 0.00610 0.00437 0.00390 0.00230
2 68 0.00987 0.00350 0.00785 0.00693 0.00610 0.00437 0.00390 0.00230 69 0.00987 0.00350 0.00808 0.00732 0.00610 0.00437 0.00390 0.00230 70 0.01673 0.00670 0.00830 0.00772 0.00610 0.00437 0.00390 0.00230 71 0.01673 0.00670 0.00835 0.00777 0.00610 0.00437 0.00390 0.00230 72 0.01673 0.00670 0.00841 0.00781 0.00610 0.00437 0.00390 0.00230 73 0.01673 0.00670 0.00846 0.00786 0.00610 0.00437 0.00390 0.00230 74 0.01673 0.00670 0.00852 0.00791 0.00610 0.00437 0.00390 0.00230 75 0.01673 0.00670 0.00857 0.00796 0.01288 0.01197 0.00980 0.00590 76 0.01673 0.00670 0.00863 0.00801 0.01288 0.01197 0.00980 0.00590 77 0.01673 0.00670 0.00868 0.00806 0.01288 0.01197 0.00980 0.00590 78 0.01673 0.00670 0.00874 0.00810 0.01288 0.01197 0.00980 0.00590 79 0.01673 0.00670 0.00879 0.00815 0.01288 0.01197 0.00980 0.00590 80 0.01673 0.00670 0.00884 0.00820 0.01288 0.01197 0.00980 0.00590 81 0.01673 0.00670 0.00894 0.00756 0.01288 0.01197 0.00980 0.00590 82 0.01673 0.00670 0.00903 0.00691 0.01288 0.01197 0.00980 0.00590 83 0.01673 0.00670 0.00913 0.00627 0.01288 0.01197 0.00980 0.00590 84 0.01673 0.00670 0.00922 0.00562 0.01288 0.01197 0.00980 0.00590 85 0.01673 0.00670 0.00932 0.00498 0.02415 0.02013 0.01680 0.00960 86 0.01673 0.00670 0.00941 0.00434 0.02415 0.02013 0.01680 0.00960 87 0.01673 0.00670 0.00951 0.00369 0.02415 0.02013 0.01680 0.00960 88 0.01673 0.00670 0.00960 0.00305 0.02415 0.02013 0.01680 0.00960 89 0.01673 0.00670 0.00970 0.00240 0.02415 0.02013 0.01680 0.00960 90 0.01673 0.00670 0.00979 0.00176 0.02415 0.02013 0.01680 0.00960 91 0.01673 0.00670 0 0 0.02415 0.02013 0.01680 0.00960 92 0.01673 0.00670 0 0 0.02415 0.02013 0.01680 0.00960 93 0.01673 0.00670 0 0 0.02415 0.02013 0.01680 0.00960 94 0.01673 0.00670 0 0 0.02415 0.02013 0.01680 0.00960 95 0.01673 0.00670 0 0 0.02415 0.02013 0.01680 0.00960 96 0.01673 0.00670 0 0 0.02415 0.02013 0.01680 0.00960 97 0.01673 0.00670 0 0 0.02415 0.02013 0.01680 0.00960 98 0.01673 0.00670 0 0 0.02415 0.02013 0.01680 0.00960 99 0.01673 0.00670 0 0 0.02415 0.02013 0.01680 0.00960 100 0.01673 0.00670 0 0 0.02415 0.02013 0.01680 0.00960
3 TABLE S2. Annual mortality rates in Germany
Mortality from CVD Total mortality [5] (ICD-10 I00-I99) [6]
Age
(years) Men Women Men Women
30 0.00064 0.00028 0.00007 0.00003 31 0.00071 0.00030 0.00008 0.00003 32 0.00074 0.00035 0.00008 0.00004 33 0.00076 0.00037 0.00008 0.00004 34 0.00079 0.00042 0.00009 0.00004 35 0.00084 0.00040 0.00013 0.00005 36 0.00088 0.00048 0.00014 0.00006 37 0.00095 0.00053 0.00015 0.00006 38 0.00110 0.00056 0.00018 0.00007 39 0.00115 0.00066 0.00018 0.00008 40 0.00128 0.00071 0.00024 0.00009 41 0.00137 0.00080 0.00026 0.00010 42 0.00153 0.00089 0.00029 0.00011 43 0.00178 0.00102 0.00033 0.00013 44 0.00199 0.00112 0.00037 0.00014 45 0.00221 0.00127 0.00049 0.00018 46 0.00247 0.00141 0.00055 0.00020 47 0.00289 0.00164 0.00064 0.00023 48 0.00321 0.00177 0.00071 0.00025 49 0.00358 0.00206 0.00080 0.00029 50 0.00400 0.00220 0.00096 0.00032 51 0.00473 0.00245 0.00113 0.00035 52 0.00501 0.00275 0.00120 0.00040 53 0.00552 0.00301 0.00132 0.00043 54 0.00619 0.00319 0.00148 0.00046 55 0.00677 0.00354 0.00167 0.00056 56 0.00729 0.00377 0.00180 0.00060 57 0.00805 0.00400 0.00198 0.00063 58 0.00879 0.00441 0.00217 0.00070 59 0.00954 0.00472 0.00235 0.00075 60 0.01039 0.00539 0.00281 0.00099 61 0.01117 0.00575 0.00302 0.00105 62 0.01199 0.00631 0.00324 0.00115 63 0.01264 0.00674 0.00342 0.00123 64 0.01410 0.00735 0.00381 0.00134 65 0.01506 0.00781 0.00422 0.00167 66 0.01654 0.00855 0.00464 0.00182 67 0.01788 0.00913 0.00502 0.00195 68 0.01915 0.00971 0.00537 0.00207 69 0.02094 0.01062 0.00587 0.00227
4 70 0.02277 0.01160 0.00726 0.00330
71 0.02493 0.01288 0.00795 0.00366 72 0.02711 0.01448 0.00865 0.00411 73 0.02985 0.01626 0.00952 0.00462 74 0.03387 0.01861 0.01081 0.00529 75 0.03744 0.02146 0.01394 0.00803 76 0.04162 0.02449 0.01550 0.00917 77 0.04675 0.02772 0.01741 0.01038 78 0.05282 0.03207 0.01967 0.01200 79 0.05885 0.03631 0.02192 0.01359 80 0.06505 0.04177 0.02751 0.01911 81 0.07285 0.04759 0.03081 0.02178 82 0.08033 0.05514 0.03397 0.02523 83 0.08790 0.06271 0.03718 0.02870 84 0.09819 0.07232 0.04153 0.03309 85 0.10863 0.08275 0.05073 0.04365 86 0.12091 0.09422 0.05646 0.04970 87 0.13525 0.10829 0.06316 0.05712 88 0.14831 0.12229 0.06926 0.06450 89 0.16727 0.14152 0.07811 0.07464 90 0.17600 0.15480 0.09229 0.09150 91 0.19982 0.17769 0.10478 0.10503 92 0.21635 0.18923 0.11345 0.11185 93 0.23466 0.20725 0.12305 0.12250 94 0.25354 0.22588 0.13295 0.13351 95 0.27293 0.24505 0.14312 0.14485 96 0.29277 0.26470 0.15352 0.15646 97 0.31298 0.28477 0.16412 0.16832 98 0.33351 0.30519 0.17488 0.18039 99 0.35430 0.32590 0.18578 0.19263 100 0.37527 0.34684 0.19678 0.20501
CVD, cardiovascular disease; ICD-10, International Classification of Diseases, 10th Revision.
5 TABLE S3. Relative risks of chronic kidney disease
SBP (mmHg)
RR of
ESRD [7] Range [7]
<120 1.00
120–129 1.61 1.27–2.05 130–139 1.97 1.54–2.51 140–159 2.57 2.06–3.22 160–179 3.82 2.97–4.92 180–209 3.88 2.82–5.33
>210 4.18 2.59–6.76
ESRD, end-stage renal disease; RR, relative risk; SBP, systolic blood pressure.
TABLE S4. Blood pressure levels in Germany (office measurements)
Age BP Men Women
(years) (mmHg) [8] [8]
30–39 Systolic 130 122 Diastolic 84 78 40–49 Systolic 135 130 Diastolic 88 82 50–59 Systolic 143 143 Diastolic 89 86 60–69 Systolic 150 153 Diastolic 88 86 70–79 Systolic 153 155 Diastolic 83 83
6 TABLE S5. Cost analysis
Cost Unit Total Parameter and cost components weight cost (€) cost (€) Cost of therapeutic drug monitoring (TDM) (per drug) [9]a
Total (GOÄ reimbursement code 4210) 1 60 60
Annual cost of antihypertensive treatment (base case scenario)
Enalapril 2 x 20 mg/day (Xanef®) [10] 2 122 244 Carvedilol 2 x 25 mg/day (Querto®) [10] 2 291 582
HCT 1 x 25 mg/day (Esidrix®) [10] 1 74 74
GP visit [11] 4 37 148
Cardiologist visit [11] 1 53 53
Ophthalmologist visit (fundoscopy) [11] 1 21 21
Brain imaging (MRI or CT scan) [12] 0.1 93 9
General laboratory investigations [12] 2 7 14
Total 1.145
Annual cost of antihypertensive treatment (alternative three-drug regimen)
Ramipril 1 x 10 mg/day (Ramipril protect®) [10] 1 76 76 Amlodipin 1 x 10 mg/day (Amloclair®) [10] 1 54 54
HCT 1 x 25 mg/day (Esidrix®) [10] 1 74 74
GP visit [11] 4 37 148
Cardiologist visit[11] 1 53 53
Ophthalmologist visit (fundoscopy) [11] 1 21 21
Brain imaging (MRI or CT scan) [12] 0.1 93 9
General laboratory investigations [12] 2 7 14
Total 449
Annual cost of antihypertensive treatment (alternative four-drug regimen)
Olmesartan 1 x 40 mg/day (Votum®) [10] 1 433 433 Indapamid 1 x 1,5 mg/day (Natrilix®) [10] 1 145 145 Lercanidipin 1 x 20 mg/day (Carmen®) [10] 1 97 97 Carvedilol 2 x 25 mg/day (Querto®) [10] 2 291 582
GP visit [11] 4 37 148
Cardiologist visit [11] 1 53 53
Ophthalmologist visit (fundoscopy) [11] 1 21 21
Brain imaging (MRI or CT scan) [12] 0.1 93 9
General laboratory investigations [12] 2 7 14
Total 1,502
Cost of myocardial infarction
Emergency ambulance services [13]b 1 682 682
G-DRG F24A [14] 0.5 8,363 4,181
G-DRG F24B [14] 0.5 5,395 2,698
Drug-eluting stent (ZE 101.01) [14] 0.5 236 118
7 Clopidogrel 75 mg/day (Plavix®) (1 year) [10] 1 1,000 1,000
Cardiac rehabilitation [15]b 0.75 3,621 2,716
Total 11,395
Cost of fatal pre-hospital myocardial infarction
Emergency ambulance services [13]b 1 682 682
Cost of one attack of angina
G-DRG F58B [14] 0.8 2,920 2,336
Drug-eluting stent (ZE 101.01) [14] 0.4 236 94
G-DRG F06E [14] 0.1 16,091 1,609
G-DRG F72B [14] 0.1 1,635 164
Cardiac rehabilitation [15]b 0.1 3,621 362
Cardiologist visit [11] 1 53 53
Clopidogrel 75 mg/day (Plavix®) (200 days) [10] 0.55 1,000 550
Total 5,168
Cost of stroke treatment (1st year)b
Total [16] 20,812
Annual cost of moderate stroke sequelaeb
Total [16] 6,158
Annual cost of severe stroke sequelae
Annual cost of moderate stroke sequelae [16]b 6,158 Annual cost of nursing home (level of care 2) [17] 0.25 15,348 3,837 Annual cost of nursing home (level of care 3) [17] 0.7 18,600 13,020 Annual cost of nursing home (cases of hardship) [17] 0.05 23,016 1,151
Total 24,166
Cost of developing heart failure (initial diagnosis)
G-DRG F62A [14] 0.5 6,854 3,427
G-DRG F62B [14] 0.5 2,794 1,397
Cardiologist visit [11] 1 53 53
Total 4,877
Cost of heart failure worsening
G-DRG F62A [14] 0.5 6,854 3,427
G-DRG F62B [14] 0.5 2,794 1,397
Cardiologist visit [11] 1 53 53
Total 4,877
Annual cost after myocardial infarction or angina
Acetylsalicylic acid 100 mg/day (Aspirin®) [10] 1 14 14
Simvastatin 40 mg/day (Zocor®) [10] 1 279 279
Cardiologist visit [11] 1 53 53
8
Total 346
Annual cost after stroke without sequelae
Acetylsalicylic acid 100 mg/day (Aspirin®) [10] 1 14 14
Simvastatin 40 mg/day (Zocor®) [10] 1 279 279
Neurologist visit [11] 1 54 54
Total 347
Annual cost of heart failure treatment
G-DRG F62A [14] 0.25 6,854 1,713
G-DRG F62B [14] 0.25 2,794 698
Acetylsalicylic acid 100 mg/day (Aspirin®) [10] 0.7 14 10
Spironolactone (Aldactone®) [10] 0.2 38 8
Simvastatin 40 mg/day (Zocor®) [10] 0.7 279 195
Cardiologist visit [11] 1 53 53
Total 2,678
Annual cost of ESRD treatmentb
Dialysis procedures [18] 33,219
Hospitalizations (incl. shunt implementation/revisions) [18] 8,586 Medication (excl. antihypertensive drugs) [18] 12,966
Total 54,770
All costs were rounded to the nearest whole Euro (€) amount. Continuous antihypertensive therapy was assumed in both arms of the Markov model (therapeutic drug monitoring and control group). Cost of further medication was added as required (e.g. statins for secondary prevention).
aBasic costs given in the GOÄ catalogue were multiplied by a factor of 1.15 [9].
All German Diagnosis Related Groups (G-DRG) based calculations assumed the 2014 Federal German base rate of €3,157 [19].
bCost estimates were updated to 2014 with the German inflation indices (https://www.destatis.de).
CT, computed tomography; EBM, Uniform Value Scale (Einheitlicher Bewertungsmaßstab);
ESRD, end-stage renal disease; GOÄ, German doctor’s fee schedule (Gebührenordnung für Ärzte); GP, general practitioner; MRI, magnetic resonance imaging; ZE, supplementary payment (Zusatzentgelt).
9 TABLE S6. Model validation: expected remaining lifetime
Model estimations Statistics Germany [5]
Initial age
(years) Men Women Men Women
30 48.57 53.29 48.56 53.29
40 38.93 43.50 38.93 43.50
50 29.67 33.97 29.67 33.98
60 21.31 24.95 21.31 24.96
70 13.90 16.52 13.89 16.53
80 7.77 9.13 7.77 9.13
90 3.85 4.24 3.84 4.25
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