On Line Appendix for Impact of Delaying Blood Pressure Control in Patients with Type-2

On Line Appendix for “Impact of Delaying Blood Pressure Control in Patients with Type-2 Diabetes: Results of a Decision Analysis”

Authors:

Neda Laiteerapong, M.D.

Priya John, M.P.H.

David O. Meltzer, M.D., Ph.D.

Elbert S. Huang, M.D., M.P.H.

The purpose of this technical appendix is to provide more detail for readers interested in understanding the structure and assumptions of the delay in blood pressure control model for type 2 diabetes. The basic structure of the model is depicted in Figure 1 of the manuscript.

For all macrovascular and microvascular complications, we used the original UKPDS prediction equations (UKPDS No.68) for all annual probabilities.1 The complication states that were assigned utilities for this analysis included amputation, blindness in one eye, congestive heart failure, end-stage renal disease, ischemic heart disease, myocardial infarction, and stroke. We used the average utilities for these states obtained from direct elicitation in a racially and ethnically-diverse population of adults with Type 2 diabetes.2 Utilities for myocardial infarction and congestive heart failure were obtained from the UKPDS study (UKPDS No.62),3 since utilities for these states were not available in Huang et al.2 Quality adjusted life expectancy (QALE) was calculated using the minimum method. In this method, the lowest utility score for any experienced complication state is used for a given year. For example, if a patient experienced a myocardial infarction and a stroke in a given year, the utility for that year would be 0.31 which is the lower utility of the two states. The total QALE for a given patient is the sum of each year’s QALY for the patient’s lifetime.

Online Appendix Table 1. Population Characteristics

Newly diagnosed diabetes population / Prevalent diabetes population / Source
Mean, SD(Range) / Mean, SD(Range)
Males / Females / Males / Females
Age / 50-59 / 50-59 / 50-59 / 50-59 / Study population
Duration of diabetes, y / 0 / 0 / 13.62, 2.57 (0-30) / 8.65, 0.69 (0-30) / Study population/ NHANES
Hemoglobin A1C, % / 6.5 / 6.5 / 6.96, 0.20 (5-17) / 7.12, 0.20 (5-17) / Study population/ NHANES
Total cholesterol, mmol/l / 5.35, 0.07 (3.11-7.68) / 5.64, 0.08 (3.11-7.68) / 5.19, 0.10 (3.11-7.68) / 5.53, 0.19 (3.11-7.68) / NHANES
High density lipoprotein cholesterol, mmol/L / 1.23, 0.02 (0.78-2.59) / 1.46, 0.03 (0.78-2.59) / 1.17, 0.02 (0.78-2.59) / 1.32, 0.05 (0.78-2.59) / NHANES
Body mass index, kg/m2 / 29.34, 0.29 (16-50) / 30.78, 0.46 (16-50) / 30.67, 0.63 (16-50) / 33.54, 0.76 (16-50) / NHANES
Smoking at diabetes diagnosis, % / Same as current smoking / Same as current smoking / 64.09, 5.13 (0-100) / 76.14, 1.61 (0-100) / NHANES
Current smoking, % / 24.80, 3.33 (0-100) / 15.48, 2.63 (0-100) / 29.13, 4.79 (0-100) / 27.90, 4.34 (0-100) / NHANES
Atrial fibrillation, % / 0.20 / 0.20 / 0.20 / 0.20 / Go et al.4
Congestive heart failure, % / 2.19, 0.77 (0-100) / 1.08, 0.59 (0-100) / 4.29, 1.31 (0-100) / 5.7, 0.99 (0-100) / NHANES

Online Appendix Table 2. Utility Values

Primary Analysis / Source / Sensitivity Analysis / Source
Amputation / 0.55 / Huang et al.2 / 0.72 / UKPDS3
Blindness in one eye / 0.38 / Huang et al.2 / 0.926 / UKPDS3
Congestive heart failure / 0.892 / UKPDS3 / 0.892 / UKPDS3
End-stage renal disease / 0.35 / Huang et al.2 / 0.61 / UKPDS3
Ischemic heart disease / 0.64 / Huang et al.2 / 0.91 / UKPDS3
Stroke / 0.31 / Huang et al.2 / 0.836 / UKPDS3
Myocardial infarction / 0.945 / UKPDS3 / 0.945 / UKPDS3

Online Appendix Table 31. Harm of Delays in Controlling Systolic Blood Pressure on Individual Diabetes Complication Rates in the Newly Diagnosed Population*†

Delay, y / Amputation / CHF / ESRD / IHD / MI / Stroke
0 / 569 (524-614) / 1147 (1085-1209) / 207 (179-235) / 936 (879-993) / 2418 (2334-2502) / 1019 (960-1078)
1 / 572 (526-618) / 1148 (1086-1210) / 207 (179-235) / 937 (880-994) / 2423 (2339-2507) / 1023 (964-1082)
5 / 582 (536-628) / 1161 (1098-1224) / 216 (188-244) / 971 (913-1029) / 2473 (2388-2558) / 1057 (997-1117)
10 / 608 (561-655) / 1192 (1128-1256) / 236 (206-266) / 1001 (942-1060) / 2543 (2458-2628) / 1144 (1082-1206)
15 / 657 (608-706) / 1231 (1167-1295) / 279 (247-311) / 1037 (977-1097) / 2627 (2541-2713) / 1240 (1175-1305)
20 / 707 (657-757) / 1282 (1216-1348) / 322 (287-357) / 1071 (1010-1132) / 2720 (2633-2807) / 1362 (1295-1429)
Lifetime / 818 (764-872) / 1383 (1315-1451) / 428 (388-468) / 1118 (1056-1180) / 2846 (2758-2934) / 1558 (1487-1629)

* Delays were modeled for a hypothetical population of adults aged 50-59 year old with newly diagnosed Type 2 diabetes. During delays, hypothetical patients were assumed to have uncontrolled systolic blood pressure (150 mmHg). Rates reported as events per 10,000 patients (95% CI).

† CHF, congestive heart failure; ESRD, end-stage renal disease; IHD, ischemic heart disease; MI, myocardial infarction

Online Appendix Table 42. Harm of Delays in Controlling Systolic Blood Pressure on Overall Diabetes Complication Rates, Life Expectancy and Quality-Adjusted Life Expectancy in the Prevalent Diabetes Population*

Delay, y / Overall diabetes complication rates† / Life expectancy / Quality-adjusted life expectancy
Events (95% CI) / Difference‡ / Years (95% CI) / Days lost / Years (95% CI) / Days lost
0 / 4384 (4255-4513) / - / 16.70 (16.98-15.93) / - / 15.93 (15.79-16.07) / -
1 / 4421 (4291-4551) / 37 / 16.68 (16.97-15.90) / 5 / 15.9 (15.76-16.04) / 11
5 / 4630 (4498-4762) / 246 / 16.56 (16.85-15.72) / 48 / 15.72 (15.58-15.86) / 77
10 / 4937 (4801-5073) / 553 / 16.39 (16.68-15.49) / 110 / 15.49 (15.35-15.64) / 161
15 / 5290 (5149-5431) / 906 / 16.27 (16.56-15.33) / 153 / 15.33 (15.19-15.47) / 219
20 / 5536 (5391-5681) / 1152 / 16.23 (16.52-15.26) / 172 / 15.26 (15.12-15.4) / 245
Lifetime / 5738 (5590-5886) / 1354 / 16.21 (16.50-15.23) / 179 / 15.23 (15.09-15.37) / 256

* Delays were modeled for a hypothetical population of adults aged 50-59 year old with Type 2 diabetes. During delays, hypothetical patients were assumed to have uncontrolled systolic blood pressure (150 mmHg). Rates reported as events per 10,000 patients (95% CI).

† Complications included amputation, congestive heart failure, end-stage renal disease, ischemic heart disease, myocardial infarction, and stroke.

‡ Difference in events between population with controlled blood pressure and populations with delays in controlling blood pressure

Online Appendix Table 35. Harm of Delays in Controlling Systolic Blood Pressure on Individual Diabetes Complication Rates in the Prevalent Diabetes Population*†

Delay, y / Amputation / CHF / ESRD / IHD / MI / Stroke
0 / 634 (586-682) / 595 (549-641) / 200 (173-227) / 678 (629-727) / 1697 (1623-1771) / 580 (534-626)
1 / 641 (593-689) / 599 (552-646) / 205 (177-233) / 682 (633-731) / 1703 (1629-1777) / 591 (545-637)
5 / 676 (627-725) / 615 (568-662) / 237 (207-267) / 701 (651-751) / 1757 (1682-1832) / 644 (596-692)
10 / 739 (688-790) / 639 (591-687) / 298 (265-331) / 729 (678-780) / 1818 (1742-1894) / 714 (664-764)
15 / 825 (771-879) / 665 (616-714) / 350 (314-386) / 756 (704-808) / 1903 (1826-1980) / 791 (738-844)
20 / 876 (821-931) / 692 (642-742) / 392 (354-430) / 777 (725-829) / 1949 (1871-2027) / 850 (795-905)
Lifetime / 919 (862-976) / 711 (661-761) / 427 (387-467) / 795 (742-848) / 1990 (1912-2068) / 896 (840-952)

† CHF, congestive heart failure; ESRD, end-stage renal disease; IHD, ischemic heart disease; MI, myocardial infarction

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Online Appendix Table 4. Population Characteristics

Newly diagnosed diabetes population / Prevalent diabetes population / Source
Mean, SD(Range) / Mean, SD(Range)
Males / Females / Males / Females
Age / 50-59 / 50-59 / 50-59 / 50-59 / Study population
Duration of diabetes, y / 0 / 0 / 13.62, 2.57 (0-30) / 8.65, 0.69 (0-30) / Study population/ NHANES
Hemoglobin A1C, % / 6.5 / 6.5 / 6.96, 0.20 (5-17) / 7.12, 0.20 (5-17) / Study population/ NHANES
Total cholesterol, mmol/l / 5.35, 0.07 (3.11-7.68) / 5.64, 0.08 (3.11-7.68) / 5.19, 0.10 (3.11-7.68) / 5.53, 0.19 (3.11-7.68) / NHANES
High density lipoprotein cholesterol, mmol/L / 1.23, 0.02 (0.78-2.59) / 1.46, 0.03 (0.78-2.59) / 1.17, 0.02 (0.78-2.59) / 1.32, 0.05 (0.78-2.59) / NHANES
Body mass index, kg/m2 / 29.34, 0.29 (16-50) / 30.78, 0.46 (16-50) / 30.67, 0.63 (16-50) / 33.54, 0.76 (16-50) / NHANES
Smoking at diabetes diagnosis, % / Same as current smoking / Same as current smoking / 64.09, 5.13 (0-100) / 76.14, 1.61 (0-100) / NHANES
Current smoking, % / 24.80, 3.33 (0-100) / 15.48, 2.63 (0-100) / 29.13, 4.79 (0-100) / 27.90, 4.34 (0-100) / NHANES
Atrial fibrillation, % / 0.20 / 0.20 / 0.20 / 0.20 / Go et al.4
Congestive heart failure, % / 2.19, 0.77 (0-100) / 1.08, 0.59 (0-100) / 4.29, 1.31 (0-100) / 5.7, 0.99 (0-100) / NHANES

Online Appendix Table 5. Utility Values

Primary Analysis / Source / Sensitivity Analysis / Source
Amputation / 0.55 / Huang et al.2 / 0.72 / UKPDS3
Blindness in one eye / 0.38 / Huang et al.2 / 0.926 / UKPDS3
Congestive heart failure / 0.892 / UKPDS3 / 0.892 / UKPDS3
End-stage renal disease / 0.35 / Huang et al.2 / 0.61 / UKPDS3
Ischemic heart disease / 0.64 / Huang et al.2 / 0.91 / UKPDS3
Stroke / 0.31 / Huang et al.2 / 0.836 / UKPDS3
Myocardial infarction / 0.945 / UKPDS3 / 0.945 / UKPDS3

References

1. Clarke PM, Gray AM, Briggs A, Farmer AJ, Fenn P, Stevens RJ, et al. A model to estimate the lifetime health outcomes of patients with type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model (UKPDS no. 68). Diabetologia. 2004;47:1747-1759.

2. Huang ES, Brown SE, Ewigman BG, Foley EC, Meltzer DO. Patient perceptions of quality of life with diabetes-related complications and treatments. Diabetes Care. 2007;30:2478-2483.

3. Clarke P, Gray A, Holman R. Estimating utility values for health states of type 2 diabetic patients using the EQ-5D (UKPDS 62). Med Decis Making. 2002;22:340-349.

4. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285:2370-2375.

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