title: 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.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The George Institute for Global Health, University of Sydney, PO Box M201, Missenden Rd, Camperdown, NSW 2050, Australia. Electronic address: rwebster@georgeinstitute.org.au.
authors.forename: Ruth
authors.initials: R
authors.lastname: Webster
authors.affiliation: The George Institute for Global Health, University of Sydney, PO Box M201, Missenden Rd, Camperdown, NSW 2050, Australia.
authors.forename: Anushka
authors.initials: A
authors.lastname: Patel
authors.affiliation: National Institute for Health Innovation, School of Population Health, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Selak
authors.affiliation: The George Institute for Global Health, University of Sydney, PO Box M201, Missenden Rd, Camperdown, NSW 2050, Australia.
authors.forename: Laurent
authors.initials: L
authors.lastname: Billot
authors.affiliation: The Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Michiel L
authors.initials: ML
authors.lastname: Bots
authors.affiliation: South Australian Health and Medical Research Institute, PO Box 11060, Adelaide, SA 5001, Australia.
authors.forename: Alex
authors.initials: A
authors.lastname: Brown
authors.affiliation: National Institute for Health Innovation, School of Population Health, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand.
authors.forename: Chris
authors.initials: C
authors.lastname: Bullen
authors.affiliation: Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, NT 0811, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Cass
authors.affiliation: Invercargill Medical Centre, 160 Don St, Invercargill 9810, New Zealand.
authors.forename: Sue
authors.initials: S
authors.lastname: Crengle
authors.affiliation: Department of General Practice and Primary Health Care, The University of Auckland, Auckland, New Zealand.
authors.forename: C
authors.initials: C
authors.lastname: Raina Elley
authors.affiliation: The Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.affiliation: The George Institute for Global Health, University of Sydney, PO Box M201, Missenden Rd, Camperdown, NSW 2050, Australia.
authors.forename: Bruce
authors.initials: B
authors.lastname: Neal
authors.affiliation: The George Institute for Global Health, University of Sydney, PO Box M201, Missenden Rd, Camperdown, NSW 2050, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Peiris
authors.affiliation: Imperial College, 59/61 North Wharf Road, St Mary's Campus, London, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: Poulter
authors.affiliation: Centre for Chronic Disease Control, 4th Floor, Plot no. 47, Sector 44, Near Metro Huda City Center, Gurgaon, Haryana 122002, India.
authors.forename: Dorairaj
authors.initials: D
authors.lastname: Prabhakaran
authors.affiliation: National Institute for Health Innovation, School of Population Health, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand.
authors.forename: Natasha
authors.initials: N
authors.lastname: Rafter
authors.affiliation: Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin 2, Ireland.
authors.forename: Alice
authors.initials: A
authors.lastname: Stanton
authors.affiliation: The George Institute for Global Health, University of Sydney, PO Box M201, Missenden Rd, Camperdown, NSW 2050, Australia.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Stepien
authors.affiliation: Imperial College, 59/61 North Wharf Road, St Mary's Campus, London, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Thom
authors.affiliation: Sydney Medical School - Westmead, University of Sydney, Sydney, Australia.
authors.forename: Tim
authors.initials: T
authors.lastname: Usherwood
authors.affiliation: National Institute for Health Innovation, School of Population Health, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand.
authors.forename: Angela
authors.initials: A
authors.lastname: Wadham
authors.affiliation: The George Institute for Global Health, University of Sydney, PO Box M201, Missenden Rd, Camperdown, NSW 2050, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Rodgers
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage; D001315:Australia / Q000453:epidemiology; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000453:epidemiology*; D016208:Databases, Factual / Q000592:standards; D004338:Drug Combinations; D004739:England / Q000453:epidemiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D007194:India / Q000453:epidemiology; D007494:Ireland / Q000453:epidemiology; D009426:Netherlands / Q000453:epidemiology; D009520:New Zealand / Q000453:epidemiology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D002317:Cardiovascular Agents; D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors
keywords: Cardiovascular disease; Meta-analysis; Polypill; Secondary prevention