Original Research15 October 2019
A Benefit–Harm Analysis
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    Visual Abstract. Personalized Benefit–Harm Analysis for Aspirin in Primary Prevention

    The benefits of aspirin for primary prevention of cardiovascular disease outweigh its bleeding harms in some patients. This individualized benefit–harm analysis from New Zealand primary care practices identifies characteristics of persons likely to have net benefit, equipoise, or net harm.

    Background:

    Whether the benefits of aspirin for the primary prevention of cardiovascular disease (CVD) outweigh its bleeding harms in some patients is unclear.

    Objective:

    To identify persons without CVD for whom aspirin would probably result in a net benefit.

    Design:

    Individualized benefit–harm analysis based on sex-specific risk scores and estimates of the proportional effect of aspirin on CVD and major bleeding from a 2019 meta-analysis.

    Setting:

    New Zealand primary care.

    Participants:

    245 028 persons (43.6% women) aged 30 to 79 years without established CVD who had their CVD risk assessed between 2012 and 2016.

    Measurements:

    The net effect of aspirin was calculated for each participant by subtracting the number of CVD events likely to be prevented (CVD risk score × proportional effect of aspirin on CVD risk) from the number of major bleeds likely to be caused (major bleed risk score × proportional effect of aspirin on major bleeding risk) over 5 years.

    Results:

    2.5% of women and 12.1% of men were likely to have a net benefit from aspirin treatment for 5 years if 1 CVD event was assumed to be equivalent in severity to 1 major bleed, increasing to 21.4% of women and 40.7% of men if 1 CVD event was assumed to be equivalent to 2 major bleeds. Net benefit subgroups had higher baseline CVD risk, higher levels of most established CVD risk factors, and lower levels of bleeding-specific risk factors than net harm subgroups.

    Limitations:

    Risk scores and effect estimates were uncertain. Effects of aspirin on cancer outcomes were not considered. Applicability to non–New Zealand populations was not assessed.

    Conclusion:

    For some persons without CVD, aspirin is likely to result in net benefit.

    Primary Funding Source:

    Health Research Council of New Zealand.

    References

    • 1. Baigent CBlackwell LCollins Ret alAntithrombotic Trialists' (ATT) CollaborationAspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet2009;373:1849-60. [PMID: 19482214] doi:10.1016/S0140-6736(09)60503-1 CrossrefMedlineGoogle Scholar
    • 2. Seshasai SRWijesuriya SSivakumaran Ret alEffect of aspirin on vascular and nonvascular outcomes: meta-analysis of randomized controlled trials. Arch Intern Med2012;172:209-16. [PMID: 22231610] doi:10.1001/archinternmed.2011.628 CrossrefMedlineGoogle Scholar
    • 3. Hennekens CHBaigent CPrevention. Aspirin in primary prevention—good news and bad news. Nat Rev Cardiol2012;9:262-3. [PMID: 22371106] doi:10.1038/nrcardio.2012.26 CrossrefMedlineGoogle Scholar
    • 4. Bowman LMafham MWallendszus Ket alASCEND Study Collaborative GroupEffects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med2018;379:1529-1539. [PMID: 30146931] doi:10.1056/NEJMoa1804988. CrossrefMedlineGoogle Scholar
    • 5. Gaziano JMBrotons CCoppolecchia Ret alARRIVE Executive CommitteeUse 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. Lancet2018;392:1036-1046. [PMID: 30158069] doi:10.1016/S0140-6736(18)31924-X CrossrefMedlineGoogle Scholar
    • 6. McNeil JJWolfe RWoods RLet alASPREE Investigator GroupEffect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med2018;379:1509-1518. [PMID: 30221597] doi:10.1056/NEJMoa1805819 CrossrefMedlineGoogle Scholar
    • 7. Zheng SLRoddick AJAssociation of aspirin use for primary prevention with cardiovascular events and bleeding events: a systematic review and meta-analysis. JAMA2019;321:277-287. [PMID: 30667501] doi:10.1001/jama.2018.20578 CrossrefMedlineGoogle Scholar
    • 8. Goff DCLloyd-Jones DMBennett Get alAmerican College of Cardiology/American Heart Association Task Force on Practice Guidelines2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation2014;129:S49-73. [PMID: 24222018] doi:10.1161/01.cir.0000437741.48606.98 CrossrefMedlineGoogle Scholar
    • 9. Fifth Joint Task Force of the European Society of CardiologyEuropean Guidelines on Cardiovascular Disease Prevention in Clinical Practice (version 2012): the Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur J Prev Cardiol2012;19:585-667. [PMID: 22763626] doi:10.1177/2047487312450228 CrossrefMedlineGoogle Scholar
    • 10. Anderson KMOdell PMWilson PWet alCardiovascular disease risk profiles. Am Heart J1991;121:293-8. [PMID: 1985385] CrossrefMedlineGoogle Scholar
    • 11. Conroy RMPyörälä KFitzgerald APet alSCORE project groupEstimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J2003;24:987-1003. [PMID: 12788299] CrossrefMedlineGoogle Scholar
    • 12. Hippisley-Cox JCoupland CVinogradova Yet alPredicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2. BMJ2008;336:1475-82. [PMID: 18573856] doi:10.1136/bmj.39609.449676.25 CrossrefMedlineGoogle Scholar
    • 13. Pylypchuk RWells SKerr Aet alCardiovascular disease risk prediction equations in 400 000 primary care patients in New Zealand: a derivation and validation study. Lancet2018;391:1897-1907. [PMID: 29735391] doi:10.1016/S0140-6736(18)30664-0 CrossrefMedlineGoogle Scholar
    • 14. Selak VJackson RPoppe Ket alPredicting bleeding risk to guide aspirin use for the primary prevention of cardiovascular disease: a cohort study. Ann Intern Med2019. [PMID: 30802900]. doi:10.7326/M18-2808 LinkGoogle Scholar
    • 15. Selak VKerr APoppe Ket alAnnual risk of major bleeding among persons without cardiovascular disease not receiving antiplatelet therapy. JAMA2018;319:2507-2520. [PMID: 29946729] doi:10.1001/jama.2018.8194 CrossrefMedlineGoogle Scholar
    • 16. Wells SRiddell TKerr Aet alCohort profile: the PREDICT cardiovascular disease cohort in New Zealand primary care (PREDICT-CVD 19). Int J Epidemiol2017;46:22. [PMID: 26686841] doi:10.1093/ije/dyv312 CrossrefMedlineGoogle Scholar
    • 17. van der Leeuw JRidker PMvan der Graaf Yet alPersonalized cardiovascular disease prevention by applying individualized prediction of treatment effects. Eur Heart J2014;35:837-43. [PMID: 24513790] doi:10.1093/eurheartj/ehu004 CrossrefMedlineGoogle Scholar
    • 18. Dehmer SPMaciosek MVFlottemesch TJet alAspirin for the primary prevention of cardiovascular disease and colorectal cancer: a decision analysis for the U.S. Preventive Services Task Force. Ann Intern Med2016;164:777-86. [PMID: 27064573]. doi:10.7326/M15-2129 LinkGoogle Scholar
    • 19. Dugani SAmes JMManson JEet alWeighing the anti-ischemic benefits and bleeding risks from aspirin therapy: a rational approach. Curr Atheroscler Rep2018;20:15. [PMID: 29464356] doi:10.1007/s11883-018-0717-y CrossrefMedlineGoogle Scholar
    • 20. Mora SAmes JMManson JELow-dose aspirin in the primary prevention of cardiovascular disease: shared decision making in clinical practice. JAMA2016;316:709-10. [PMID: 27323335] doi:10.1001/jama.2016.8362 CrossrefMedlineGoogle Scholar
    • 21. Puhan MAYu TStegeman Iet alBenefit-harm analysis and charts for individualized and preference-sensitive prevention: example of low dose aspirin for primary prevention of cardiovascular disease and cancer. BMC Med2015;13:250. [PMID: 26423305] doi:10.1186/s12916-015-0493-2 CrossrefMedlineGoogle Scholar
    • 22. Coon SABrooks ADWolff SEPrimary prevention aspirin use in high-risk patients: a pharmacist intervention and comparison of risk stratification tools. J Am Pharm Assoc (2003)2017;57:585-590. [PMID: 28811088] doi:10.1016/j.japh.2017.07.003 CrossrefMedlineGoogle Scholar
    • 23. Dorresteijn JAVisseren FLRidker PMet alAspirin for primary prevention of vascular events in women: individualized prediction of treatment effects. Eur Heart J2011;32:2962-9. [PMID: 22090661] doi:10.1093/eurheartj/ehr423 CrossrefMedlineGoogle Scholar
    • 24. Bibbins-Domingo KU.S. Preventive Services Task ForceAspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med2016;164:836-45. [PMID: 27064677]. doi:10.7326/M16-0577 LinkGoogle Scholar