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

Jill Belch (Lead / Corresponding author), Angus MacCuish, Iain Campbell, Stuart Cobbe, Roy Taylor, Robin Prescott, Robert Lee, Jean Bancroft, Shirley MacEwan, James Shepherd, Peter Macfarlane, Andrew Morris, Roland Jung, Christopher Kelly, Alan Connacher, Norman Peden, Andrew Jamieson, David Matthews, Graeme Leese, John McKnight & 7 others Iain O'Brien, Colin Semple, John Petrie, Derek Gordon, Stuart Pringle, Ron MacWalter, Diabet Registry Grp, Prevent Progression Arterial Dis &, Royal Coll Phys Edinburgh

    Research output: Contribution to journalArticle

    398 Citations (Scopus)

    Abstract

    Objective To determine whether aspirin and antioxidant therapy, combined or alone, are more effective than placebo in reducing the development of cardiovascular events in patients with diabetes mellitus and asymptomatic peripheral arterial disease.

    Design Multicentre, randomised, double blind, 2 x 2 factorial, placebo controlled trial.

    Setting 16 hospital centres in Scotland, supported by 188 primary care groups.

    Participants 1276 adults aged 40 or more with type 1 or type 2 diabetes and an ankle brachial pressure index of 0.99 or less but no symptomatic cardiovascular disease. Interventions Daily, 100 mg aspirin tablet plus antioxidant capsule ( n= 320), aspirin tablet plus placebo capsule ( n= 318), placebo tablet plus antioxidant capsule ( n= 320), or placebo tablet plus placebo capsule ( n= 318).

    Main outcome measures Two hierarchical composite primary end points of death from coronary heart disease or stroke, non- fatal myocardial infarction or stroke, or amputation above the ankle for critical limb ischaemia; and death from coronary heart disease or stroke.

    Results Noevidence was found of any interaction between aspirin and antioxidant. Overall, 116 of 638 primary events occurred in the aspirin groups compared with 117 of 638 in the no aspirin groups ( 18.2% v 18.3%): hazard ratio 0.98 ( 95% confidence interval 0.76 to 1.26). Forty three deaths from coronary heart disease or stroke occurred in the aspirin groups compared with 35 in the no aspirin groups ( 6.7% v 5.5%): 1.23 ( 0.79 to 1.93). Among the antioxidant groups 117 of 640 ( 18.3%) primary events occurred compared with 116 of 636 ( 18.2%) in the no antioxidant groups ( 1.03, 0.79 to 1.33). Forty two ( 6.6%) deaths from coronary heart disease or stroke occurred in the antioxidant groups compared with 36 ( 5.7%) in the no antioxidant groups ( 1.21, 0.78 to 1.89).

    Conclusion This trial does not provide evidence to support the use of aspirin or antioxidants in primary prevention of cardiovascular events and mortality in the population with diabetes studied.

    Trial registration Current Controlled Trials ISRCTN53295293.

    Original languageEnglish
    Article numbera1840
    Pages (from-to)1-10
    Number of pages10
    JournalBMJ
    Volume337
    Issue number7677
    DOIs
    Publication statusPublished - 1 Nov 2008

    Keywords

    • CORONARY-HEART-DISEASE
    • CARDIOVASCULAR EVENTS
    • ANTIPLATELET THERAPY
    • SECONDARY PREVENTION
    • GENERAL-POPULATION
    • METAANALYSIS
    • RISK
    • ASSOCIATION
    • MELLITUS
    • STROKE

    Cite this

    Belch, J., MacCuish, A., Campbell, I., Cobbe, S., Taylor, R., Prescott, R., ... Diabet Registry Grp, Prevent Progression Arterial Dis &, Royal Coll Phys Edinburgh (2008). 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, 337(7677), 1-10. [a1840]. https://doi.org/10.1136/bmj.a1840
    Belch, Jill ; MacCuish, Angus ; Campbell, Iain ; Cobbe, Stuart ; Taylor, Roy ; Prescott, Robin ; Lee, Robert ; Bancroft, Jean ; MacEwan, Shirley ; Shepherd, James ; Macfarlane, Peter ; Morris, Andrew ; Jung, Roland ; Kelly, Christopher ; Connacher, Alan ; Peden, Norman ; Jamieson, Andrew ; Matthews, David ; Leese, Graeme ; McKnight, John ; O'Brien, Iain ; Semple, Colin ; Petrie, John ; Gordon, Derek ; Pringle, Stuart ; MacWalter, Ron ; Diabet Registry Grp, Prevent Progression Arterial Dis &, Royal Coll Phys Edinburgh. / 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. In: BMJ. 2008 ; Vol. 337, No. 7677. pp. 1-10.
    @article{0aaf16bfc7344df59a5fd999d8d2de3e,
    title = "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",
    abstract = "Objective To determine whether aspirin and antioxidant therapy, combined or alone, are more effective than placebo in reducing the development of cardiovascular events in patients with diabetes mellitus and asymptomatic peripheral arterial disease.Design Multicentre, randomised, double blind, 2 x 2 factorial, placebo controlled trial.Setting 16 hospital centres in Scotland, supported by 188 primary care groups.Participants 1276 adults aged 40 or more with type 1 or type 2 diabetes and an ankle brachial pressure index of 0.99 or less but no symptomatic cardiovascular disease. Interventions Daily, 100 mg aspirin tablet plus antioxidant capsule ( n= 320), aspirin tablet plus placebo capsule ( n= 318), placebo tablet plus antioxidant capsule ( n= 320), or placebo tablet plus placebo capsule ( n= 318).Main outcome measures Two hierarchical composite primary end points of death from coronary heart disease or stroke, non- fatal myocardial infarction or stroke, or amputation above the ankle for critical limb ischaemia; and death from coronary heart disease or stroke.Results Noevidence was found of any interaction between aspirin and antioxidant. Overall, 116 of 638 primary events occurred in the aspirin groups compared with 117 of 638 in the no aspirin groups ( 18.2{\%} v 18.3{\%}): hazard ratio 0.98 ( 95{\%} confidence interval 0.76 to 1.26). Forty three deaths from coronary heart disease or stroke occurred in the aspirin groups compared with 35 in the no aspirin groups ( 6.7{\%} v 5.5{\%}): 1.23 ( 0.79 to 1.93). Among the antioxidant groups 117 of 640 ( 18.3{\%}) primary events occurred compared with 116 of 636 ( 18.2{\%}) in the no antioxidant groups ( 1.03, 0.79 to 1.33). Forty two ( 6.6{\%}) deaths from coronary heart disease or stroke occurred in the antioxidant groups compared with 36 ( 5.7{\%}) in the no antioxidant groups ( 1.21, 0.78 to 1.89).Conclusion This trial does not provide evidence to support the use of aspirin or antioxidants in primary prevention of cardiovascular events and mortality in the population with diabetes studied.Trial registration Current Controlled Trials ISRCTN53295293.",
    keywords = "CORONARY-HEART-DISEASE, CARDIOVASCULAR EVENTS, ANTIPLATELET THERAPY, SECONDARY PREVENTION, GENERAL-POPULATION, METAANALYSIS, RISK, ASSOCIATION, MELLITUS, STROKE",
    author = "Jill Belch and Angus MacCuish and Iain Campbell and Stuart Cobbe and Roy Taylor and Robin Prescott and Robert Lee and Jean Bancroft and Shirley MacEwan and James Shepherd and Peter Macfarlane and Andrew Morris and Roland Jung and Christopher Kelly and Alan Connacher and Norman Peden and Andrew Jamieson and David Matthews and Graeme Leese and John McKnight and Iain O'Brien and Colin Semple and John Petrie and Derek Gordon and Stuart Pringle and Ron MacWalter and {Diabet Registry Grp, Prevent Progression Arterial Dis &, Royal Coll Phys Edinburgh}",
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    Belch, J, MacCuish, A, Campbell, I, Cobbe, S, Taylor, R, Prescott, R, Lee, R, Bancroft, J, MacEwan, S, Shepherd, J, Macfarlane, P, Morris, A, Jung, R, Kelly, C, Connacher, A, Peden, N, Jamieson, A, Matthews, D, Leese, G, McKnight, J, O'Brien, I, Semple, C, Petrie, J, Gordon, D, Pringle, S, MacWalter, R & Diabet Registry Grp, Prevent Progression Arterial Dis &, Royal Coll Phys Edinburgh 2008, '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, vol. 337, no. 7677, a1840, pp. 1-10. https://doi.org/10.1136/bmj.a1840

    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. / Belch, Jill (Lead / Corresponding author); MacCuish, Angus; Campbell, Iain; Cobbe, Stuart; Taylor, Roy; Prescott, Robin; Lee, Robert; Bancroft, Jean; MacEwan, Shirley; Shepherd, James; Macfarlane, Peter; Morris, Andrew; Jung, Roland; Kelly, Christopher; Connacher, Alan; Peden, Norman; Jamieson, Andrew; Matthews, David; Leese, Graeme; McKnight, John; O'Brien, Iain; Semple, Colin; Petrie, John; Gordon, Derek; Pringle, Stuart; MacWalter, Ron; Diabet Registry Grp, Prevent Progression Arterial Dis &, Royal Coll Phys Edinburgh.

    In: BMJ, Vol. 337, No. 7677, a1840, 01.11.2008, p. 1-10.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - The prevention of progression of arterial disease and diabetes (POPADAD) trial

    T2 - factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease

    AU - Belch, Jill

    AU - MacCuish, Angus

    AU - Campbell, Iain

    AU - Cobbe, Stuart

    AU - Taylor, Roy

    AU - Prescott, Robin

    AU - Lee, Robert

    AU - Bancroft, Jean

    AU - MacEwan, Shirley

    AU - Shepherd, James

    AU - Macfarlane, Peter

    AU - Morris, Andrew

    AU - Jung, Roland

    AU - Kelly, Christopher

    AU - Connacher, Alan

    AU - Peden, Norman

    AU - Jamieson, Andrew

    AU - Matthews, David

    AU - Leese, Graeme

    AU - McKnight, John

    AU - O'Brien, Iain

    AU - Semple, Colin

    AU - Petrie, John

    AU - Gordon, Derek

    AU - Pringle, Stuart

    AU - MacWalter, Ron

    AU - Diabet Registry Grp, Prevent Progression Arterial Dis &, Royal Coll Phys Edinburgh

    PY - 2008/11/1

    Y1 - 2008/11/1

    N2 - Objective To determine whether aspirin and antioxidant therapy, combined or alone, are more effective than placebo in reducing the development of cardiovascular events in patients with diabetes mellitus and asymptomatic peripheral arterial disease.Design Multicentre, randomised, double blind, 2 x 2 factorial, placebo controlled trial.Setting 16 hospital centres in Scotland, supported by 188 primary care groups.Participants 1276 adults aged 40 or more with type 1 or type 2 diabetes and an ankle brachial pressure index of 0.99 or less but no symptomatic cardiovascular disease. Interventions Daily, 100 mg aspirin tablet plus antioxidant capsule ( n= 320), aspirin tablet plus placebo capsule ( n= 318), placebo tablet plus antioxidant capsule ( n= 320), or placebo tablet plus placebo capsule ( n= 318).Main outcome measures Two hierarchical composite primary end points of death from coronary heart disease or stroke, non- fatal myocardial infarction or stroke, or amputation above the ankle for critical limb ischaemia; and death from coronary heart disease or stroke.Results Noevidence was found of any interaction between aspirin and antioxidant. Overall, 116 of 638 primary events occurred in the aspirin groups compared with 117 of 638 in the no aspirin groups ( 18.2% v 18.3%): hazard ratio 0.98 ( 95% confidence interval 0.76 to 1.26). Forty three deaths from coronary heart disease or stroke occurred in the aspirin groups compared with 35 in the no aspirin groups ( 6.7% v 5.5%): 1.23 ( 0.79 to 1.93). Among the antioxidant groups 117 of 640 ( 18.3%) primary events occurred compared with 116 of 636 ( 18.2%) in the no antioxidant groups ( 1.03, 0.79 to 1.33). Forty two ( 6.6%) deaths from coronary heart disease or stroke occurred in the antioxidant groups compared with 36 ( 5.7%) in the no antioxidant groups ( 1.21, 0.78 to 1.89).Conclusion This trial does not provide evidence to support the use of aspirin or antioxidants in primary prevention of cardiovascular events and mortality in the population with diabetes studied.Trial registration Current Controlled Trials ISRCTN53295293.

    AB - Objective To determine whether aspirin and antioxidant therapy, combined or alone, are more effective than placebo in reducing the development of cardiovascular events in patients with diabetes mellitus and asymptomatic peripheral arterial disease.Design Multicentre, randomised, double blind, 2 x 2 factorial, placebo controlled trial.Setting 16 hospital centres in Scotland, supported by 188 primary care groups.Participants 1276 adults aged 40 or more with type 1 or type 2 diabetes and an ankle brachial pressure index of 0.99 or less but no symptomatic cardiovascular disease. Interventions Daily, 100 mg aspirin tablet plus antioxidant capsule ( n= 320), aspirin tablet plus placebo capsule ( n= 318), placebo tablet plus antioxidant capsule ( n= 320), or placebo tablet plus placebo capsule ( n= 318).Main outcome measures Two hierarchical composite primary end points of death from coronary heart disease or stroke, non- fatal myocardial infarction or stroke, or amputation above the ankle for critical limb ischaemia; and death from coronary heart disease or stroke.Results Noevidence was found of any interaction between aspirin and antioxidant. Overall, 116 of 638 primary events occurred in the aspirin groups compared with 117 of 638 in the no aspirin groups ( 18.2% v 18.3%): hazard ratio 0.98 ( 95% confidence interval 0.76 to 1.26). Forty three deaths from coronary heart disease or stroke occurred in the aspirin groups compared with 35 in the no aspirin groups ( 6.7% v 5.5%): 1.23 ( 0.79 to 1.93). Among the antioxidant groups 117 of 640 ( 18.3%) primary events occurred compared with 116 of 636 ( 18.2%) in the no antioxidant groups ( 1.03, 0.79 to 1.33). Forty two ( 6.6%) deaths from coronary heart disease or stroke occurred in the antioxidant groups compared with 36 ( 5.7%) in the no antioxidant groups ( 1.21, 0.78 to 1.89).Conclusion This trial does not provide evidence to support the use of aspirin or antioxidants in primary prevention of cardiovascular events and mortality in the population with diabetes studied.Trial registration Current Controlled Trials ISRCTN53295293.

    KW - CORONARY-HEART-DISEASE

    KW - CARDIOVASCULAR EVENTS

    KW - ANTIPLATELET THERAPY

    KW - SECONDARY PREVENTION

    KW - GENERAL-POPULATION

    KW - METAANALYSIS

    KW - RISK

    KW - ASSOCIATION

    KW - MELLITUS

    KW - STROKE

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    U2 - 10.1136/bmj.a1840

    DO - 10.1136/bmj.a1840

    M3 - Article

    VL - 337

    SP - 1

    EP - 10

    JO - British Medical Journal

    JF - British Medical Journal

    SN - 0959-8146

    IS - 7677

    M1 - a1840

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