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北京大学学报（医学版） ›› 2023, Vol. 55 ›› Issue (3): 480-487. doi: 10.19723/j.issn.1671-167X.2023.03.014

• 论著 • 上一篇    下一篇

阿司匹林用于心血管病一级预防的不同策略比较：一项马尔可夫模型研究

张明露1,刘秋萍1,巩超1,王佳敏1,周恬静1,刘晓非1,沈鹏2,林鸿波2,唐迅1,4,*(),高培1,3,4,*()   

  1. 1. 北京大学公共卫生学院流行病与卫生统计学系，北京 100191
    2. 宁波市鄞州区疾病预防控制中心，浙江 宁波 315101
    3. 北京大学临床研究所真实世界证据评价中心，北京 100191
    4. 重大疾病流行病学教育部重点实验室(北京大学)，北京 100191
  • 收稿日期:2023-02-27 出版日期:2023-06-18 发布日期:2023-06-12
  • 通讯作者: 唐迅,高培 E-mail:tangxun@bjmu.edu.cn;peigao@bjmu.edu.cn
  • 基金资助:
    国家自然科学基金(81973132);国家重点研发计划(2020YFC2003503)

Comparison of aspirin treatment strategies for primary prevention of cardiovascular diseases: A decision-analytic Markov modelling study

Ming-lu ZHANG1,Qiu-ping LIU1,Chao GONG1,Jia-min WANG1,Tian-jing ZHOU1,Xiao-fei LIU1,Peng SHEN2,Hong-bo LIN2,Xun TANG1,4,*(),Pei GAO1,3,4,*()   

  1. 1. Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China
    2. Yinzhou District Center for Disease Control and Prevention, Ningbo 315101, Zhejiang, China
    3. Center of Real-world Evidence Evaluation, Peking University Clinical Research Institute, Beijing 100191, China
    4. Key Laboratory of Epidemiology of Major Diseases(Peking University), Ministry of Education, Beijing 100191, China
  • Received:2023-02-27 Online:2023-06-18 Published:2023-06-12
  • Contact: Xun TANG,Pei GAO E-mail:tangxun@bjmu.edu.cn;peigao@bjmu.edu.cn
  • Supported by:
    the National Natural Sciences Foundation of China(81973132);the National Key Research and Development Program of China(2020YFC2003503)

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摘要：

目的: 在中国鄞州电子健康档案研究(Chinese Electronic Health Records Research in Yinzhou，CHERRY)中，比较实施不同指南推荐的阿司匹林用于心血管病一级预防策略预期的获益与风险。方法: 采用马尔可夫(Markov)模型模拟所比较的不同策略：策略①：对40~69岁心血管病高风险人群使用低剂量阿司匹林干预(2020年《中国心血管病一级预防指南》)；策略②：对40~59岁心血管病高风险人群使用低剂量阿司匹林干预(2022年美国预防服务工作组《阿司匹林用于心血管病一级预防的推荐声明》)；策略③：对40~69岁心血管病高风险且基线血压控制良好(150/90 mmHg以下)的人群使用低剂量阿司匹林干预(2019年《中国心血管病风险评估和管理指南》)。循环周期设为1年，模拟10年，获益指标包括增加的质量调整生命年(quality-adjusted life year, QALY)和每预防一例缺血性事件的需治疗人数(number needed to treat, NNT)，风险指标包括每增加一例出血性事件的需应对危害人数(number needed to harm, NNH)，计算人群净获益(可预防的缺血性事件数减去增加的出血性事件数)及其NNT。结果: 共纳入212 153名研究对象，采用策略①~③进行阿司匹林干预的人数分别为34 235、2 813和25 111。策略③预期增加的QALY最多，为403[95%不确定性区间(uncertainty interval, UI)：222~511]年，其获益指标的NNT仅比策略①增加了4(95%UI：3~4)人，但风险指标的NNH增加了39(95%UI：19~132)人，显示策略③的安全性更好。三种策略净获益的NNT分别为131(95%UI：102~239)人、256(95%UI：181~737)人和132(95%UI：104~232)人，在净获益效率相似时，QALY和安全性更好的策略③具有优势。结论: 采用三种策略在CHERRY人群中均能获得净获益，相比之下考虑血压控制水平的策略可兼顾效果获益与安全性风险，并获得较好的干预效率。

关键词: 心血管疾病, 一级预防, 阿司匹林, 马尔可夫模型

Abstract:

Objective: To compare the expected population impact of benefit and risk of aspirin treatment strategies for the primary prevention of cardiovascular diseases recommended by different guidelines in the Chinese Electronic Health Records Research in Yinzhou (CHERRY) study. Methods: A decision-analytic Markov model was used to simulate and compare different strategies of aspirin treatment, including: Strategy ①: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk, recommended by the 2020 Chinese Guideline on the Primary Prevention of Cardiovascular Diseases; Strategy ②: Aspirin treatment for Chinese adults aged 40-59 years with a high 10-year cardiovascular risk, recommended by the 2022 United States Preventive Services Task Force Recommendation Statement on Aspirin Use to Prevent Cardiovascular Disease; Strategy ③: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk and blood pressure well-controlled (< 150/90 mmHg), recommended by the 2019 Guideline on the Assessment and Management of Cardio-vascular Risk in China. The high 10-year cardiovascular risk was defined as the 10-year predicted risk over 10% based on the 2019 World Health Organization non-laboratory model. The Markov model simulated different strategies for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Quality-adjusted life year (QALY) and the number needed to treat (NNT) for each ischemic event (including myocardial infarction and ischemic stroke) were calculated to assess the effectiveness of the different strategies. The number needed to harm (NNH) for each bleeding event (including hemorrhagic stroke and gastrointestinal bleeding) was calculated to assess the safety. The NNT for each net benefit (i.e., the difference of the number of ischemic events could be prevented and the number of bleeding events would be added) was also calculated. One-way sensitivity analysis on the uncertainty of the incidence rate of cardiovascular diseases and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted. Results: A total of 212 153 Chinese adults, were included in this study. The number of people who were recommended for aspirin treatment Strategies ①-③ was 34 235, 2 813, and 25 111, respectively. The Strategy ③ could gain the most QALY of 403 [95% uncertainty interval (UI): 222-511] years. Compared with Strategy ①, Strategy ③ had similar efficiency but better safety, with the extra NNT of 4 (95%UI: 3-4) and NNH of 39 (95%UI: 19-132). The NNT per net benefit was 131 (95%UI: 102-239) for Strategy ①, 256 (95%UI: 181-737) for Strategy ②, and 132 (95%UI: 104-232) for Strategy ③, making Strategy ③ the most favorable option with a better QALY and safety, along with similar efficiency in terms of net benefit. The results were consistent in the sensitivity analyses. Conclusion: The aspirin treatment strategies recommended by the updated guidelines on the primary prevention of cardiovascular diseases showed a net benefit for high-risk Chinese adults from developed areas. However, to balance effectiveness and safety, aspirin is suggested to be used for primary prevention of cardiovascular diseases with consideration for blood pressure control, resulting in better intervention efficiency.

Key words: Cardiovascular diseases, Primary prevention, Aspirin, Markov model

中图分类号: 

  • R54

图1

阿司匹林用于心血管病一级预防干预策略的马尔可夫模型状态转换图"

表1

马尔可夫模型的参数及其来源"

ItemsMen Women Data sources
40-59 years 60-79 years 40-59 years 60-79 years
Transition probabilities (1/100 000)
   Incidence Estimated from the current study
      MI (P1) 39 97 29 71
      IS (P2) 430 1 063 407 1 144
      HS (P3) 101 151 86 152
      GIB (P4) 8 18 14 17
   Death Estimated from the current study
      Defined events*
         MI (P5) 5 786 8 492 7 426 10 903
         IS (P6) 1 552 2 789 916 2 773
         HS (P7) 7 369 13 125 5 904 11 492
         GIB (P8) 0 920 0 889
      Other causes
         MI (P9) 1 533 3 671 854 3 622
         IS (P10) 1 687 5 683 916 3 669
         HS (P11) 3 226 7 213 2 150 6 584
         GIB (P12) 4 706 12 311 1 014 6 753
         Status 1 (P13) 534 1 294 258 923
Intervention effects, ${\bar x}$±s
   Hazard ratio for MI 0.70±0.09 0.92±0.09 Meta-analysis[10]
   Hazard ratio for IS 1.12±0.08 0.96±0.08 Meta-analysis[10]
   Hazard ratio for HS 1.44±0.09 1.48±0.09 Meta-analysis[10]
   Hazard ratio for GIB 1.56±0.06 1.56±0.06 Meta-analysis[11]

表2

研究人群的基线特征"

Characteristics Men (n=98 366) Women (n=113 787) P value*
Age/years, ${\bar x}$±s 55.55±9.85 54.67±9.52 < 0.001
Education (senior high school or high), n (%) 15 569 (15.83) 12 165 (10.69) < 0.001
Urban, n (%) 30 410 (30.92) 37 639 (33.08) < 0.001
Current smoker, n (%) 37 833 (38.46) 1 548 (1.36) < 0.001
Diabetes, n (%) 6 980 (7.09) 8 789 (7.72) < 0.001
Hypertension, n (%) 25 823 (26.25) 31 687 (27.85) < 0.001
SBP/mmHg, ${\bar x}$±s 131.68±15.90 130.35±16.72 < 0.001
DBP/mmHg, ${\bar x}$±s 82.83±9.61 81.25±9.64 < 0.001
TC/(mmol/L), ${\bar x}$±s 4.81±0.96 5.04±0.98 < 0.001
HDL-C/(mmol/L), ${\bar x}$±s 1.28±0.35 1.35±0.33 < 0.001
LDL-C/(mmol/L), ${\bar x}$±s 2.79±0.82 2.94±0.85 < 0.001
BMI/(kg/m2), ${\bar x}$±s 23.37±2.72 23.20±2.93 < 0.001

表3

阿司匹林用于心血管病一级预防不同策略的效果、安全性及净获益比较"

Items Strategy ① vs. Strategy 0 Strategy ② vs. Strategy 0 Strategy ③ vs. Strategy 0 Strategy ① vs. Strategy ② Strategy ③ vs. Strategy ① Strategy ③ vs. Strategy ②
Total numbers for assessment 212 153 212 153 212 153
Total numbers for aspirin treatment 34 235 2 813 25 111
Life years gained 67 (-33, 147) 2 (-7, 10) 278 (191, 317) 65 (-27, 138) 211 (158, 236) 276 (197, 307)
QALY gained 329 (84, 509) 12 (1, 26) 403 (222, 511) 317 (89, 484) 74 (0, 140) 391 (227, 486)
Ischemic events could be prevented 368 (257, 427) 19 (13, 22) 260 (183, 300) 349 (244, 405) -108 (-127, -73) 241 (170, 278)
   MI events could be prevented 27 (8, 40) 1 (0, 2) 19 (6, 28) 26 (7, 38) -8 (-13, -1) 18 (6, 26)
   IS events could be prevented 341 (234, 400) 18 (12, 21) 241 (168, 281) 323 (222, 380) -100 (-119, -67) 223 (156, 260)
Bleeding events would be added 107 (52, 156) 8 (4, 12) 70 (32, 105) 99 (48, 144) -37 (-51, -20) 62 (28, 93)
   HS events would be added 87 (32, 135) 7 (3, 11) 60 (22, 95) 80 (30, 125) -27 (-40, -10) 53 (20, 84)
   GIB events would be added 20 (12, 29) 1 (1, 2) 10 (6, 14) 19 (12, 27) -10 (-14, -7) 9 (5, 12)
Numbers of net benefit 261 (143, 337) 11 (4, 16) 190 (108, 242) 250 (139, 322) -71 (-96, -35) 179 (104, 226)
Deaths from defined events* 6 (-8, 18) 0 (-1, 1) 15 (4, 23) 6 (-7, 18) 9 (5, 12) 15 (6, 22)
All deaths could be prevented 19 (-6, 39) 1 (-1, 3) 74 (52, 83) 18 (-5, 36) 55 (42, 61) 73 (53, 81)
NNT per ischemic event 93 (80, 133) 148 (128, 214) 97 (84, 137) -55 (-80, -48) 4 (3, 4) -51 (-77, -45)
NNH per bleeding event 320 (219, 660) 352 (231, 716) 359 (239, 789) -32 (-58, -12) 39 (19, 132) 7 (6, 74)
NNT per net benefit 131 (102, 239) 256 (181, 737) 132 (104, 232) -125 (-506, -78) 1 (-7, 3) -124 (-514, -76)

图2

分性别比较不同策略的效果和安全性的影响"

图3

心血管病发病率的变化对质量调整生命年影响的单因素敏感性分析"

1 Raber I , McCarthy CP , Vaduganathan M , et al. The rise and fall of aspirin in the primary prevention of cardiovascular disease[J]. Lancet, 2019, 393 (10186): 2155- 2167.
doi: 10.1016/S0140-6736(19)30541-0
2 Li XY , Li L , Na SH , et al. Implications of the heterogeneity between guideline recommendations for the use of low dose aspirin in primary prevention of cardiovascular disease[J]. Am J Prev Cardiol, 2022, 11, 100363.
doi: 10.1016/j.ajpc.2022.100363
3 中华医学会心血管病学分会, 中国康复医学会心脏预防与康复专业委员会, 中国老年学和老年医学会心脏专业委员会, 等. 中国心血管病一级预防指南[J]. 中华心血管病杂志, 2020, 48 (12): 1000- 1038.
doi: 10.3760/cma.j.cn112148-20201009-00796
4 US Preventive Services Task Force , Davidson KW , Barry MJ , et al. Aspirin use to prevent cardiovascular disease: US Preventive Services Task Force Recommendation Statement[J]. JAMA, 2022, 327 (16): 1577- 1584.
doi: 10.1001/jama.2022.4983
5 World Health Organization . Prevention of cardiovascular disease: Guidelines for assessment and management of total cardiovascular risk[M]. Geneva: WHO, 2007.
6 中国心血管病风险评估和管理指南编写联合委员会. 中国心血管病风险评估和管理指南[J]. 中华预防医学杂志, 2019, 53 (1): 13- 35.
doi: 10.3760/cma.j.issn.0253-9624.2019.01.004
7 Lin H , Tang X , Shen P , et al. Using big data to improve cardiovascular care and outcomes in China: A protocol for the Chinese Electronic Health Records Research in Yinzhou (CHERRY) study[J]. BMJ Open, 2018, 8 (2): e019698.
doi: 10.1136/bmjopen-2017-019698
8 WHO CVD Risk Chart Working Group . World Health Organization cardiovascular disease risk charts: Revised models to estimate risk in 21 global regions[J]. Lancet Glob Health, 2019, 7 (10): e1332- e1345.
doi: 10.1016/S2214-109X(19)30318-3
9 Sussman JB , Vijan S , Choi H , et al. Individual and population benefits of daily aspirin therapy: A proposal for personalizing national guidelines[J]. Circ Cardiovasc Qual Outcomes, 2011, 4 (3): 268- 275.
doi: 10.1161/CIRCOUTCOMES.110.959239
10 Abdelaziz HK , Saad M , Pothineni NVK , et al. Aspirin for primary prevention of cardiovascular events[J]. J Am Coll Cardiol, 2019, 73 (23): 2915- 2929.
doi: 10.1016/j.jacc.2019.03.501
11 Zheng SL , Roddick AJ . Association of aspirin use for primary prevention with cardiovascular events and bleeding events: A systematic review and meta-analysis[J]. JAMA, 2019, 321 (3): 277- 287.
doi: 10.1001/jama.2018.20578
12 Salomon JA , Haagsma JA , Davis A , et al. Disability weights for the Global Burden of Disease 2013 study[J]. Lancet Glob Health, 2015, 3 (11): e712- e723.
doi: 10.1016/S2214-109X(15)00069-8
13 Dehmer SP , O'Keefe LR , Evans CV , et al. Aspirin use to prevent cardiovascular disease and colorectal cancer: Updated modeling study for the US Preventive Services Task Force[J]. JAMA, 2022, 327 (16): 1598- 1607.
doi: 10.1001/jama.2022.3385
14 ASCEND Study Collaborative Group , Bowman L , Mafham M , et al. Effects of aspirin for primary prevention in persons with diabetes mellitus[J]. N Engl J Med, 2018, 379 (16): 1529- 1539.
doi: 10.1056/NEJMoa1804988
15 Selak V , Jackson R , Poppe K , et al. Predicting bleeding risk to guide aspirin use for the primary prevention of cardiovascular disease: A cohort study[J]. Ann Intern Med, 2019, 170 (6): 357- 368.
doi: 10.7326/M18-2808
16 Greving JP , Buskens E , Koffijberg H , et al. Cost-effectiveness of aspirin treatment in the primary prevention of cardiovascular disease events in subgroups based on age, gender, and varying cardiovascular risk[J]. Circulation, 2008, 117 (22): 2875- 2883.
doi: 10.1161/CIRCULATIONAHA.107.735340
17 McNeil JJ , Wolfe R , Woods RL , et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly[J]. N Engl J Med, 2018, 379 (16): 1509- 1518.
doi: 10.1056/NEJMoa1805819
18 Guirguis-Blake JM , Evans CV , Perdue LA , et al. Aspirin use to prevent cardiovascular disease and colorectal cancer: Updated evidence report and systematic review for the US Preventive Services Task Force[J]. JAMA, 2022, 327 (16): 1585- 1597.
doi: 10.1001/jama.2022.3337
19 Selak V , Jackson R , Poppe K , et al. Personalized prediction of cardiovascular benefits and bleeding harms from aspirin for primary prevention: A benefit-harm analysis[J]. Ann Intern Med, 2019, 171 (8): 529- 539.
doi: 10.7326/M19-1132
20 Zhou M , Wang H , Zeng X , et al. Mortality, morbidity, and risk factors in China and its provinces, 1990—2017: A systematic analysis for the Global Burden of Disease study 2017[J]. Lancet, 2019, 394 (10204): 1145- 1158.
doi: 10.1016/S0140-6736(19)30427-1
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