An international randomised placebo-controlled trial of a four-component combination pill ("Polypill") in people with raised cardiovascular risk

PILL Collaborative Group

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    119 Citations (Scopus)

    Abstract

    Background: There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ('polypills') to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability. Methods: We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12 weeks follow-up. Findings: At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2). There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001), which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment. Conclusions: This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12607000099426.

    Original languageEnglish
    Article numbere19857
    JournalPLoS One
    Volume6
    Issue number5
    DOIs
    Publication statusPublished - 01-01-2011

    Fingerprint

    Blood pressure
    low density lipoprotein cholesterol
    LDL Cholesterol
    placebos
    systolic blood pressure
    Randomized Controlled Trials
    Placebos
    Blood Pressure
    aspirin
    adverse effects
    cardiovascular diseases
    Aspirin
    hydrochlorothiazide
    Lisinopril
    Hydrochlorothiazide
    Simvastatin
    hypotension
    drug therapy
    Cardiovascular Diseases
    Medicine

    All Science Journal Classification (ASJC) codes

    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)

    Cite this

    @article{3d4cd498e7e14480844a5433711ce5fe,
    title = "An international randomised placebo-controlled trial of a four-component combination pill ({"}Polypill{"}) in people with raised cardiovascular risk",
    abstract = "Background: There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ('polypills') to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability. Methods: We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5{\%}. The primary outcomes were systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12 weeks follow-up. Findings: At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95{\%} CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95{\%} CI 0.6 to 0.9) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23{\%} vs 18{\%} (RR 1.33, 95{\%} CI 0.89 to 2.00, p = 0.2). There was an excess of side effects known to the component medicines (58{\%} vs 42{\%}, p = 0.001), which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment. Conclusions: This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12607000099426.",
    author = "{PILL Collaborative Group} and Anthony Rodgers and Anushka Patel and Otavio Berwanger and Michiel Bots and Richard Grimm and Grobbee, {Diederick E.} and Rod Jackson and Bruce Neal and Jim Neaton and Neil Poulter and Natasha Rafter and Raju, {P. Krishnam} and Srinath Reddy and Simon Thom and Hoorn, {Stephen Vander} and Ruth Webster and Angela Wadham and Vanessa Selak and Hoorn, {Steve Vander} and Joy Jiang and Rina Prasad and John Faatui and Tamsin Scott and Amanda Milne and Barry Gray and Colleen Ng and Johan Strydom and Bindu Patel and Paula Zeman and Donaldson, {Oscar Hazel} and Joseph Canalese and Patrick Groenstein and Kumara Mendis and David Sullivan and Kerry Kearns and Nicole Li and Toni Monico and Evelyn Nangle and Chloe Runeckles and Laranjeira, {Ligia Nasi} and Buchler, {Anna Maria} and {Di Vanna}, Andrea and Alexandre Biasi and Guimaraes, {Helio Penna} and Nora Falconi and {Da Silva}, Cyntia and {De Menezes}, {Elaine Bastos} and Salam, {M. Abdul} and Dash, {Ashok Kumar} and Kalyana Chakravarthy",
    year = "2011",
    month = "1",
    day = "1",
    doi = "10.1371/journal.pone.0019857",
    language = "English",
    volume = "6",
    journal = "PLoS One",
    issn = "1932-6203",
    publisher = "Public Library of Science",
    number = "5",

    }

    An international randomised placebo-controlled trial of a four-component combination pill ("Polypill") in people with raised cardiovascular risk. / PILL Collaborative Group.

    In: PLoS One, Vol. 6, No. 5, e19857, 01.01.2011.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - An international randomised placebo-controlled trial of a four-component combination pill ("Polypill") in people with raised cardiovascular risk

    AU - PILL Collaborative Group

    AU - Rodgers, Anthony

    AU - Patel, Anushka

    AU - Berwanger, Otavio

    AU - Bots, Michiel

    AU - Grimm, Richard

    AU - Grobbee, Diederick E.

    AU - Jackson, Rod

    AU - Neal, Bruce

    AU - Neaton, Jim

    AU - Poulter, Neil

    AU - Rafter, Natasha

    AU - Raju, P. Krishnam

    AU - Reddy, Srinath

    AU - Thom, Simon

    AU - Hoorn, Stephen Vander

    AU - Webster, Ruth

    AU - Wadham, Angela

    AU - Selak, Vanessa

    AU - Hoorn, Steve Vander

    AU - Jiang, Joy

    AU - Prasad, Rina

    AU - Faatui, John

    AU - Scott, Tamsin

    AU - Milne, Amanda

    AU - Gray, Barry

    AU - Ng, Colleen

    AU - Strydom, Johan

    AU - Patel, Bindu

    AU - Zeman, Paula

    AU - Donaldson, Oscar Hazel

    AU - Canalese, Joseph

    AU - Groenstein, Patrick

    AU - Mendis, Kumara

    AU - Sullivan, David

    AU - Kearns, Kerry

    AU - Li, Nicole

    AU - Monico, Toni

    AU - Nangle, Evelyn

    AU - Runeckles, Chloe

    AU - Laranjeira, Ligia Nasi

    AU - Buchler, Anna Maria

    AU - Di Vanna, Andrea

    AU - Biasi, Alexandre

    AU - Guimaraes, Helio Penna

    AU - Falconi, Nora

    AU - Da Silva, Cyntia

    AU - De Menezes, Elaine Bastos

    AU - Salam, M. Abdul

    AU - Dash, Ashok Kumar

    AU - Chakravarthy, Kalyana

    PY - 2011/1/1

    Y1 - 2011/1/1

    N2 - Background: There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ('polypills') to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability. Methods: We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12 weeks follow-up. Findings: At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2). There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001), which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment. Conclusions: This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12607000099426.

    AB - Background: There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ('polypills') to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability. Methods: We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12 weeks follow-up. Findings: At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2). There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001), which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment. Conclusions: This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12607000099426.

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    U2 - 10.1371/journal.pone.0019857

    DO - 10.1371/journal.pone.0019857

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    SN - 1932-6203

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