Table 1
Selected parameters used in this simulation study.
| Category | Mean | Variance (SE) | Lower limit of 95 CI% | Upper limited of 95 CI% | Distribution | Source |
|---|---|---|---|---|---|---|
| Effect of statin treatment on LDL-C change (%) | ||||||
| Low-dose statins* | –30.0 | —† | —† | —† | — | American Heart Association/American College of Cardiology Cholesterol Management Guideline [17] |
| Moderate-dose statins‡ | –49.0 | —† | —† | —† | — | |
| Relative change in ASCVD risk per mmol/L LDL-C reduction (%) | ||||||
| Acute coronary events§ | –29.0 | — | –35.0 | –23.0 | Log-normal | Meta-analysis of Individual Data from the Cholesterol Treatment Trialists’ (CTT) Collaborators [18] |
| Ischemic stroke§ | –21.0 | — | –26.0 | –15.0 | Log-normal | |
| Direct costs | ||||||
| Yearly costs for statins before the new centralized medicine procurement policy was implemented | ||||||
| Low-dose statin (Int$/year) | 284.2 | 117.8 | 68.9 | 530.5 | Gamma | Integrated Management Platform of Beijing Medicine Sunshine Purchase [13] |
| Moderate-dose statin (Int$/year) | 568.4 | 235.5 | 137.8 | 1061.0 | Gamma | |
| Yearly costs for statins under the new centralized medicine procurement policy | ||||||
| Low-dose statin (Int$/year) | 48.2 | 7.0 | 34.6 | 61.9 | Gamma | National centralized procurement policy bid-winning announcement file |
| Moderate-dose statin (Int$/year) | 96.5 | 13.9 | 69.2 | 123.8 | Gamma | |
| Lowest cost for low-dose statin (Int$/year) | 40.2 | —† | —† | —† | — | |
| Statin treatment related costs | ||||||
| Examination for risk assessment of ASCVD (Int$/time) || | 19.3 | 1.5 | 16.4 | 22.3 | Gamma | — |
| Safety screening in the first year (Int$/year) || | 139.2 | 10.8 | 118.2 | 160.3 | Gamma | — |
| Safety screening after first year (Int$/year) || | 121.8 | 9.4 | 103.4 | 140.3 | Gamma | — |
| Yearly costs for diabetes treatment (Int$/year) | 518.5 | 40.1 | 439.9 | 597.0 | Gamma | China’s study on medical expenditure of diabetes mellitus [19] |
| Costs for rhabdomyolysis (Int$/visit) | 2512.2 | 400.4 | 1727.3 | 3297.1 | Gamma | China’s Health and Family Planning Statistical Yearbook [20] |
| Annual health-care and ASCVD treatment costs | ||||||
| Annual health-care costs (Int$/year) | 947.1 | 73.2 | 803.6 | 1090.6 | Gamma | China’s Health and Family Planning Statistical Yearbook [20] |
| Hospitalization costs for acute coronary events (Int$/visit) | 8384.0 | 1336.4 | 5764.6 | 11003.4 | Gamma | |
| Hospitalization costs for ischemic stroke (Int$/visit) | 2923.3 | 642.6 | 1663.9 | 4182.7 | Gamma | |
| First aid cost for acute coronary events (Int$/visit) | 1413.8 | 225.4 | 972.1 | 1855.5 | Gamma | |
| First aid cost for ischemic stroke (Int$/visit) | 470.8 | 103.5 | 268.0 | 673.6 | Gamma | |
| Yearly costs in chronic stage for acute coronary events (Int$/year) | 1695.4 | 131.1 | 1438.5 | 1952.3 | Gamma | China Health and Retirement Longitudinal Survey [21] |
| Yearly costs in chronic stage for ischemic stroke (Int$/year) | 1417.9 | 109.6 | 1203.1 | 1632.7 | Gamma | The Fifth National Health Services Survey in Henan Province [22] |
| Incidence of adverse events (%) | ||||||
| Diabetes Low-dose statin Moderate-dose statin | 0.6 1.2 | — | 0.42 0.92 | 0.85 1.52 | Log-normal | HPS2-THRIVE study (Data of Chinese participants were used) [16] |
| Rhabdomyolysis Low-dose statin Moderate-dose statin | 0.02 0.04 | — | 0 0 | 0.10 0.13 | Log-normal | |
| Myopathy Low-dose statin Moderate-dose statin | 0.22 0.44 | — | 0.13 0.31 | 0.41 0.70 | Log-normal | |
| Other reason for stopping treatment non-adherence | 12.4 | —† | —† | —† | —† | |
[i] ASCVD, atherosclerotic cardiovascular disease; CI, confidence interval; SE, standard error; LDL-C, low-density lipoprotein cholesterol; QALY, quality-adjusted life-year; 1 Int$ = 3.539 Chinese Yuan (RMB) and all costs were inflated to 2019.
*, Equivalent potency regimens of simvastatin 20 mg/day, atorvastatin 10 mg/day, or rosuvastatin 5 mg/day.
†, Parameters in sensitivity analysis were unchanged.
‡, Equivalent potency regimens of simvastatin 40 mg/day, atorvastatin 20 mg/day, or rosuvastatin 10 mg/day.
§, Relative risk change= (1-relative risk)*100%
||, The costs were estimated base on the examination items, test frequency, and costs. The costs of biochemical tests were from the Beijing Municipal Commission of Development and Reform.
Figure 1
Conceptual diagram of the simulation model.
ASCVD, atherosclerotic cardiovascular disease; QALYs, Quality adjusted life years, ICER, incremental cost effectiveness ratio.
*, People suffered from ASCVD in 10 year among the cohort population.
†, Less people developed ASCVD in the cohort after intervention compared to the scenario of no intervention.
‡, Costs before intervention included: per capita total expenditure on health, hospitalization and post-event outpatient ASCVD management costs, and indirect costs due to onset of ASCVD.
§, Costs after intervention included: costs before intervention, statin treatment related cost and side effects treatment costs.
||, Under statin treatment, the statin treatment related adverse effects would decrease quality of life and incur treatment cost for people who receive statin treatment.
Table 2
Criterions and parameters of statin treatment recommendation for people with different risk.
| Total | Low risk | Moderate risk | High risk* | |
|---|---|---|---|---|
| 10-year ASCVD risk threshold | — | <5% | 5.0–9.9% | ≥10.0% |
| Guideline-recommended LDL-C intervention threshold (mmol/L)† | — | ≥3.4 | ≥3.4 | ≥2.6 |
| Proportion of people in each risk category in CMCS (%) | 100.0 | 70.6 | 15.4 | 14.0 |
| Proportion of people eligible for statin treatment in CMCS (%)‡ | 26.0 | 15.4 | 31.0 | 73.6 |
[i] ASCVD, atherosclerotic cardiovascular disease; CMCS, Chinese Multi-provincial Cohort Study; LDL-C, low-density lipoprotein cholesterol.
*, High-risk defined as: LDL-C ≥ 4.9 mmol/L or total cholesterol ≥ 7.2 mmol/L; diabetes and LDL-C 1.8–4.8 mmol/L or TC 3.1–7.2 mmol/L and age ≥ 40 years; or 10-year ASCVD risk ≥ 10%.
†, Recommended by the 2016 Chinese Guidelines for the Management of Dyslipidemia in Adults.
‡, People met the guideline recommendation and without use of lipid-lowering agents in each risk category.
Table 3
Cost-effectiveness of statin treatment vs. no statin treatment over 10 years stratified by ASCVD risk from health-care sector perspective and using statin prices from the new centralized medicine procurement policy.
| ASCVD Risk | Low-dose statin strategy* | Moderate-dose statin strategy** | ||||
|---|---|---|---|---|---|---|
| Low risk | Moderate risk | High risk | Low risk | Moderate risk | High risk | |
| Relative reduction of ASCVD incidence (%) | 4.1 (3.2,5.2) | 6.4 (5.1,8.3) | 15.5 (12.2,20.2) | 6.2 (4.9,7.8) | 9.7 (7.8,12.3) | 23.4 (19.1, 29.8) |
| NNT10 | 193.0 (150.6, 246.0) | 67.3 (51.7, 84.4) | 42.8 (33.0, 53.4) | 126.8 (101.0, 159.1) | 44.3 (34.7, 54.6) | 28.4 (22.3, 34.8) |
| Average 10-year treatment cost for each eligible person (Int $)‡ | 15,00 (1,200, 1,800) | 1,200 (1,000, 1,600) | 1,100 (900, 1,400) | 1,800 (1,400, 2,300) | 1,600 (1,200, 2,000) | 1,400 (1,100, 1,800) |
| ICER (Int$/QALY) | 380,700 | 92,300 | 51,300 | 347,500 | 78,000 | 43,100 |
| Probability of highly cost-effectiveness (%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Probability of cost-effectiveness (%) | 0 | 0.2 | 64.9 | 0 | 2.6 | 90.8 |
[i] ASCVD, atherosclerotic cardiovascular disease; NNT10, number needed to treat for 10-year intervention; QALY, quality adjusted life year.
*, Equivalent potency regimens of simvastatin 20 mg/day, atorvastatin 10 mg/day, or rosuvastatin 5 mg/day.
**, Equivalent potency regimens of simvastatin 40 mg/day, atorvastatin 20 mg/day, or rosuvastatin 10 mg/day.
‡, Estimated base on direct cost such as change of ASCVD treatment cost due to decrease of ASCVD incidence, statin medicine cost expenditure, statin treatment related cost, routine health-care cost, and adverse events treatment cost.
Costs are in 2019 International dollars (Int$).
Highly cost-effective: cost per QALY gained was in the range between Int$ 0 and Int$ 18,266.
Cost-effective: cost per QALY gained was in the range between Int$ 18,267 and Int$ 54,798.
Table 4
Estimated 10-year treatment effect and direct costs change among 35–64 years old ASCVD-free people if the new centralized medicine procurement policy implemented in the whole nation.
| ASCVD risk Category | Low-dose statin strategy | Moderate-dose statin strategy | ||||
|---|---|---|---|---|---|---|
| Low risk | Moderate risk | High risk | Low risk | Moderate risk | High risk | |
| Prevented incidence number of ASCVD (N) | 323,000 (253,000, 413,000) | 399,000 (317,000, 521,000) | 1,350,000 (1,083,000, 1,748,000) | 492,000 (391,000, 617,000) | 607,000 (491,000, 776,000) | 2,037,000 (1,664,000, 2,592,000) |
| Additional treatment costs (Billion Int$)* | 91.7 (71.4,107.1) | 34.4 (27.6,44.1) | 65.3 (53.6,83.3) | 115.1 (87.9,144.5) | 43.0 (33.1,55.2) | 80.8 (65.5,107.1) |
| Saving statins related treatment costs (Billion Int$) | 126.4 (35.7,244.1) | 53.6 (16.5,110.3) | 114.0 (35.7,232.2) | 253.1 (81.7,489.9) | 107.6 (35.8,215.1) | 229.7 (71.4,458.4) |
| Statin-induced diabetes (N) | 374,000 (258,000, 538,000) | 161,000 (114,000, 236,000) | 347,000 (244,000, 508,000) | 748,000 (584,000, 965,000) | 322,000 (258,000, 423,000) | 694,000 (554,000, 912,000) |
[i] *, Statin prices were taken from the national centralized procurement policy bid-winning announcement file.
Number aged 35–64 years old eligible for controlling LDL-C level in low, moderate, and high risk people in China was 62809000, 27579000, and 59525000 respectively. Details could be seen in the Supplementary Appendix.
Int$ = 3.539 Chinese Yuan (RMB).
Figure 2
Proportion of outpatient costs of low-dose statins treatment for people without ASCVD by risk level.
ASCVD, atherosclerotic cardiovascular disease.
Low-dose statins: simvastatin 20 mg/day, atorvastatin 10 mg/day, or rosuvastatin 5 mg/day.
Figure 3
Cost-effectiveness of statin treatment among people with different risk of ASCVD. Data are incremental cost-effectiveness ratios (Int$ per QALY gained).
ASCVD, atherosclerotic cardiovascular disease; ICER, incremental cost-effectiveness ratio.
In healthcare sector perspective direct cost such as change of ASCVD treatment cost due to decrease of ASCVD incidence, statin medicine cost, statin treatment related cost, routine healthcare cost, and adverse events treatment cost were included.
In societal perspective both direct and indirect costs were included. The indirect cost included patient-time costs, unpaid caregiver-time, transportation costs, and labor market earnings lost.
Figure 4
Cost-effectiveness acceptability curves for people with different 10-year ASCVD risk treated with different dose of statin.