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Journal of Peking University (Health Sciences) ›› 2023, Vol. 55 ›› Issue (3): 480-487. doi: 10.19723/j.issn.1671-167X.2023.03.014

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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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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

CLC Number: 

  • R54

Figure 1

Markov model diagram for aspirin treatment strategies for primary prevention of cardiovascular diseases The defined events in the Status 6 include MI, IS, HS and GIB. P1-P13, transition probabilities. CVD, cardiovascular diseases; GIB, gastrointestinal bleeding; MI, myocardial infarction; IS, ischemic stroke; HS, hemorrhagic stroke."

Table 1

Parameters and data sources in the Markov model"

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]

Table 2

Baseline characteristics of the study population"

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

Table 3

Comparisons of effectiveness, safety and net benefit by different strategies with aspirin treatment for primary prevention of cardiovascular diseases"

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)

Figure 2

Impact evaluation of effectiveness and safety of different strategies by gender Strategy 0: usual care for comparison; Strategy ①: aspirin treatment for Chinese adults aged 40-69 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 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 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 Cardiovascular Risk in China."

Figure 3

One-way sensitivity analyses on quality-adjusted life year by different incidence rates of cardiovascular diseases The figure annotation as in Figure 2."

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