Efficacy of Aspirin in the Primary Prevention of Cardiovascular Diseases and Cancer in the Elderly: A Population-Based Cohort Study in Korea

  • Minji Jung
  • Sukhyang LeeEmail author
Original Research Article



Aspirin is widely used to prevent cardiovascular diseases (CVDs). However, the balance of its benefits and risks in the primary prevention of CVDs and cancer is unclear, especially in elderly Asians. The present study aimed to evaluate the efficacy of aspirin in the primary prevention of major adverse cardiac and cerebrovascular events (MACCE), bleeding risk, and cancer in elderly Koreans with cardiovascular (CV) risk factors.


This retrospective cohort study used data from the Korean National Health Insurance Service–Senior cohort database (2002–2015). Patients aged 60–90 years with hypertension, type 2 diabetes mellitus (T2DM), or dyslipidemia were identified. Aspirin users were compared with non-users using propensity score matching at a 1:3 ratio. The primary outcome was MACCE, a composite of CV mortality, myocardial infarction, and ischemic stroke. The secondary outcomes were the components of MACCE, all-cause mortality, angina pectoris, heart failure, the incidence and mortality of cancer, and the risks of hemorrhagic stroke and gastrointestinal bleeding. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a Cox proportional hazard model.


A total of 3366 aspirin users and 10,089 non-users were finally included in the study. During a mean follow-up of 7.8 years, the incidence of MACCE was 15.2% in aspirin users and 22.4% in non-users. The risk of MACCE was significantly lower in aspirin users than in non-users (HR 0.76; 95% CI 0.69–0.85), and this risk was significantly reduced in patients using aspirin over 5 years (HR 0.52; 95% CI 0.46–0.60). Aspirin use was associated with a 21% reduction in the risk of primary cancer (HR 0.79; 95% CI 0.70–0.88) and cancer-related mortality (HR 0.72; 95% CI 0.61–0.84). No significant differences in bleeding risks were observed between the two groups.


Aspirin reduced the risks of MACCE and cancer without increasing the bleeding risk in elderly Koreans with hypertension, T2DM, or dyslipidemia. Moreover, the benefits of the long-term use of aspirin in reducing the risks of MACCE were demonstrated. However, the decision of using aspirin for primary prevention must be carefully made on an individual basis, while estimating the benefit–risk balance of aspirin.


Compliance with Ethical Standards


No external funding was used in the conduct of this study.

Conflict of interest

Jung and Lee declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript.


  1. 1.
    Statistics Korea. Korean Statistical Information Service. 2018. Accessed 04 Jul 2019.
  2. 2.
    Roth GA, Johnson C, Abajobir A, Abd-Allah F, Abera SF, Abyu G, et al. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J Am Coll Cardiol. 2017;70(1):1–25.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Rothwell PM, Algra A, Chen Z, Diener HC, Norrving B, Mehta Z. Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials. The Lancet. 2016;388(10042):365–75.CrossRefGoogle Scholar
  4. 4.
    Trialists’ Collaboration A. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324(7329):71–86.CrossRefGoogle Scholar
  5. 5.
    Gorelick PB, Weisman SM. Risk of hemorrhagic stroke with aspirin use: an update. Stroke. 2005;36(8):1801–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. The Lancet. 2009;373:1849–60.CrossRefGoogle Scholar
  7. 7.
    Mahmoud AN, Gad MM, Elgendy AY, Elgendy IY, Bavry AA. Efficacy and safety of aspirin for primary prevention of cardiovascular events: a meta-analysis and trial sequential analysis of randomized controlled trials. Eur Heart J. 2018;40(7):607–17.CrossRefGoogle Scholar
  8. 8.
    Zheng SL, Roddick AJ. Association of aspirin use for primary prevention with cardiovascular events and bleeding events: a systematic review and meta-analysis. JAMA. 2019;321(3):277–87.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Lin MH, Lee CH, Lin C, Zou YF, Lu CH, Hsieh CH, et al. Low-dose aspirin for the primary prevention of cardiovascular disease in diabetic individuals: a meta-analysis of randomized control trials and trial sequential analysis. J Clin Med. 2019;8(5):609.PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Algra AM, Rothwell PM. Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol. 2012;13(5):518–27.PubMedCrossRefGoogle Scholar
  11. 11.
    Rothwell PM, Price JF, Fowkes FGR, Zanchetti A, Roncaglioni MC, Tognoni G, et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. The Lancet. 2012;379(9826):1602–12.CrossRefGoogle Scholar
  12. 12.
    Chubak J, Whitlock EP, Williams SB, Kamineni A, Burda BU, Buist DS, et al. Aspirin for the prevention of cancer incidence and mortality: systematic evidence reviews for the US Preventive Services Task Force. Ann Intern Med. 2016;164(12):814–25.PubMedCrossRefGoogle Scholar
  13. 13.
    McNeil JJ, Nelson MR, Woods RL, Lockery JE, Wolfe R, Reid CM, et al. Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med. 2018;379(16):1519–28.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Bibbins-Domingo K, Preventive Services Task Force. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: US Preventive Services Task Force recommendation statement. A Intern Med. 2016;164(12):836–45.CrossRefGoogle Scholar
  15. 15.
    Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: the Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016;37(29):2315–81.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Arnett DK, Blumenthal RS, Albert MA, Michos ED, Buroker AB, Miedema MD, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. J Am Coll Cardiol. 2019;140:e596–646.Google Scholar
  17. 17.
    Stuntz M, Bernstein B. Recent trends in the prevalence of low-dose aspirin use for primary and secondary prevention of cardiovascular disease in the United States, 2012–2015. Prev Med Rep. 2017;5:183–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Ikeda Y, Shimada K, Teramoto T, Uchiyama S, Yamazaki T, Oikawa S, et al. Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial. JAMA. 2014;312(23):2510–20.PubMedCrossRefGoogle Scholar
  19. 19.
    Sugawara M, Goto Y, Yamazaki T, Teramoto T, Oikawa S, Shimada K, et al. Low-dose aspirin for primary prevention of cardiovascular events in elderly Japanese patients with atherosclerotic risk factors: subanalysis of a randomized clinical trial (JPPP-70). Am J Cardiovasc Drugs. 2019;19(3):299–311.PubMedCrossRefGoogle Scholar
  20. 20.
    Seong SC, Kim Y-Y, Park SK, Khang YH, Kim HC, Park JH, et al. Cohort profile: the National Health Insurance Service-National Health Screening cohort (NHIS-HEALS) in Korea. BMJ Open. 2017;7(9):e016640.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Lee J, Lee JS, Park S-H, Shin SA, Kim K. Cohort profile: the National Health Insurance Service-National Sample Cohort (NHIS-NSC), South Korea. Int J Epidemiol. 2016;46(2):e15.Google Scholar
  22. 22.
    Tang KL, Quan H, Rabi DM. Measuring medication adherence in patients with incident hypertension: a retrospective cohort study. BMC Health Serv Res. 2017;17(1):135.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New ICD-10 version of the Charlson Comorbidity Index predicted in-hospital mortality. J Clin Epidemiol. 2004;57(12):1288–94.CrossRefGoogle Scholar
  24. 24.
    Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73(24):e285–350.PubMedCrossRefGoogle Scholar
  25. 25.
    Linden A, Samuels SJ. Using balance statistics to determine the optimal number of controls in matching studies. J Eval in ClinPract. 2013;19:968–75.Google Scholar
  26. 26.
    Teramoto T, Shimada K, Uchiyama S, Sugawara M, Goto Y, Yamada N, et al. Rationale, design, and baseline data of the Japanese Primary Prevention Project (JPPP)—a randomized, open-label, controlled trial of aspirin versus no aspirin in patients with multiple risk factors for vascular events. Am Heart J. 2010;159(3):361–369.e4.PubMedCrossRefGoogle Scholar
  27. 27.
    Ando K, Shimada K, Yamazaki T, Uchiyama S, Uemura Y, Ishizuka N, et al. Influence of blood pressure on the effects of low-dose asprin in elderly patients with multiple atherosclerotic risks. J Hypertens. 2019;37(6):1301–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM, Manson JE, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005;352(13):1293–304.PubMedCrossRefGoogle Scholar
  29. 29.
    Berger JS, Roncaglioni MC, Avanzini F, Pangrazzi I, Tognoni G, Brown DL. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA. 2006;295(3):306–13.PubMedCrossRefGoogle Scholar
  30. 30.
    Hansson L, Zanchetti A, Carruthers SG, Dahlöf B, Elmfeldt D, Julius S, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. The Lancet. 1998;351(9118):1755–62.CrossRefGoogle Scholar
  31. 31.
    Ogawa H, Nakayama M, Morimoto T, Uemura S, Kanauchi M, Doi N, et al. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008;300(18):2134–41.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Group* SCotPHSR. Final report on the aspirin component of the ongoing Physicians’ Health Study. N Engl J Med. 1989;321(3):129–35.CrossRefGoogle Scholar
  33. 33.
    Group ASC. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med. 2018;379(16):1529–39.CrossRefGoogle Scholar
  34. 34.
    Gaziano JM, Brotons C, Coppolecchia R, Cricelli C, Darius H, Gorelick PB, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. The Lancet. 2018;392(10152):1036–46.CrossRefGoogle Scholar
  35. 35.
    McNeil JJ, Wolfe R, Woods RL, Tonkin AM, Donnan GA, Nelson MR, et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med. 2018;379(16):1509–18.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    American Diabetes Association. Cardiovascular disease and risk management: standards of medical care in diabetes—2019. Diabetes Care. 2019;42(Supplement 1):S103–23.CrossRefGoogle Scholar
  37. 37.
    Upadhaya S, Madala S, Baniya R, Saginala K, Khan J. Impact of acetylsalicylic acid on primary prevention of cardiovascular diseases: a meta-analysis of randomized trials. Eur J Prev Cardiol. 2019;26(7):746–9.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Tsoi KK, Ho JM, Chan FC, Sung JJ. Long-term use of low-dose aspirin for cancer prevention: a 10-year population cohort study in Hong Kong. Int J Cancer. 2019;145(1):267–73.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Kim YI, Kim SY, Kim JH, Lee JH, Kim YW, Ryu KW, et al. Long-term low-dose aspirin use reduces gastric cancer incidence: a nationwide cohort study. Cancer Res Treat. 2016;48(2):798.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Elwood PC, Pickering JE, Morgan G, Galante J, Weightman AL, Morris D, et al. Systematic review update of observational studies further supports aspirin role in cancer treatment: time to share evidence and decision-making with patients? PLoS One. 2018;13(9):e0203957.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, et al. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004;350(2):114–24.PubMedCrossRefGoogle Scholar
  42. 42.
    Belch J, MacCuish A, Campbell I, Cobbe S, Taylor R, Prescott R, et al. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ. 2008;337:a1840.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Framework MRCsGPR. Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. The Lancet. 1998;351(9098):233–41.CrossRefGoogle Scholar
  44. 44.
    Elwood PC, Morgan G, Galante J, Chia JW, Dolwani S, Graziano JM, et al. Systematic review and meta-analysis of randomised trials to ascertain fatal gastrointestinal bleeding events attributable to preventive low-dose aspirin: no evidence of increased risk. PLoS One. 2016;11(11):e0166166.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Huang WY, Saver JL, Wu YL, Lin CJ, Lee M, Ovbiagele B. Frequency of intracranial hemorrhage with low-dose aspirin in individuals without symptomatic cardiovascular disease: a systematic review and meta-analysis. JAMA Neurol. 2019. Scholar
  46. 46.
    Klatsky AL, Friedman GD, Sidney S, Kipp H, Kubo A, Armstrong MA. Risk of hemorrhagic stroke in Asian American ethnic groups. Neuroepidemiology. 2005;25(1):26–31.PubMedCrossRefGoogle Scholar
  47. 47.
    van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. The Lancet Neurol. 2010;9(2):167–76.PubMedCrossRefGoogle Scholar
  48. 48.
    An SJ, Kim TJ, Yoon BW. Epidemiology, risk factors, and clinical features of intracerebral hemorrhage: an update. Journal of Stroke. 2017;19(1):3.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Soriano LC, Lanas A, Soriano-Gabarró M, Rodríguez LAG. Incidence of upper and lower gastrointestinal bleeding in new users of low-dose aspirin. Clin Gastroenterol Hepatol. 2019;17(5):887–889.e6.CrossRefGoogle Scholar
  50. 50.
    Pignone M, DeWalt DA. More evidence to help guide decision making about aspirin for primary prevention. Ann Intern Med. 2018;169(11):804–5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Clinical Pharmacy, College of PharmacyAjou UniversitySuwonRepublic of Korea

Personalised recommendations