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Int J Cardiol. 2016 Feb 15;205:147-156. doi: 10.1016/j.ijcard.2015.12.015. Epub 2015 Dec 14.

Effectiveness of fixed dose combination medication ('polypills') compared with usual care in patients with cardiovascular disease or at high risk: A prospective, individual patient data meta-analysis of 3140 patients in six countries.

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The George Institute for Global Health, University of Sydney, PO Box M201, Missenden Rd, Camperdown, NSW 2050, Australia. Electronic address:
The George Institute for Global Health, University of Sydney, PO Box M201, Missenden Rd, Camperdown, NSW 2050, Australia.
National Institute for Health Innovation, School of Population Health, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand.
The Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands.
South Australian Health and Medical Research Institute, PO Box 11060, Adelaide, SA 5001, Australia.
Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, NT 0811, Australia.
Invercargill Medical Centre, 160 Don St, Invercargill 9810, New Zealand.
Department of General Practice and Primary Health Care, The University of Auckland, Auckland, New Zealand.
Imperial College, 59/61 North Wharf Road, St Mary's Campus, London, United Kingdom.
Centre for Chronic Disease Control, 4th Floor, Plot no. 47, Sector 44, Near Metro Huda City Center, Gurgaon, Haryana 122002, India.
Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin 2, Ireland.
Sydney Medical School - Westmead, University of Sydney, Sydney, Australia.



To conduct a prospective, individual participant data (IPD) meta-analysis of randomised controlled trials comparing a polypill-based approach with usual care in high risk individuals.


Three trials comparing polypill-based care with usual care in individuals with CVD or high calculated cardiovascular risk contributed IPD. Primary outcomes were self-reported adherence to combination therapy (anti-platelet, statin and ≥ two blood pressure (BP) lowering agents), and difference in mean systolic BP (SBP) and LDL-cholesterol at 12 months. Analyses used random effects models. Among 3140 patients from Australia, England, India, Ireland, New Zealand and The Netherlands (75% male, mean age 62 years), median follow-up was 15 months. At baseline, 84%, 87% and 61% respectively were taking a statin, anti-platelet agent and at least two BP lowering agents. At 12 months, compared to usual care, participants in the polypill arm had higher adherence to combination therapy (80% vs. 50%, RR 1.58; 95% CI, 1.32 to 1.90; p < 0.001), lower SBP (-2.5 mmHg; 95% CI, -4.5 to -0.4; p = 0.02) and lower LDL-cholesterol (-0.1 mmol/L; 95% CI, -0.2 to 0.0; p = 0.04). Baseline treatment levels were a major effect modifier for adherence and SBP (p-homog < 0.0001 and 0.02 respectively) with greatest improvements seen among those under-treated at baseline.


Polypill therapy significantly improved adherence, SBP and LDL-cholesterol in high risk patients compared with usual care, especially among those who were under-treated at baseline.


Cardiovascular disease; Meta-analysis; Polypill; Secondary prevention

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