title: A pragmatic randomized trial of a polypill-based strategy to improve use of indicated preventive treatments in people at high cardiovascular disease risk.
abstract: BACKGROUND
  Most individuals at high cardiovascular disease (CVD) risk worldwide do not receive any or optimal preventive drugs. We aimed to determine whether fixed dose combinations of generic drugs ('polypills') would promote use of such medications.
  
  
  METHODS
  We conducted a randomized, open-label trial involving 623 participants from Australian general practices. Participants had established CVD or an estimated five-year CVD risk of ≥15%, with indications for antiplatelet, statin and ≥2 blood pressure lowering drugs ('combination treatment'). Participants randomized to the 'polypill-based strategy' received a polypill containing aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg. Participants randomized to 'usual care' continued with separate medications and doses as prescribed by their doctor. Primary outcomes were self-reported combination treatment use, systolic blood pressure and total cholesterol.
  
  
  RESULTS
  After a median of 18 months, the polypill-based strategy was associated with greater use of combination treatment (70% vs. 47%; relative risk 1.49, (95% confidence interval (CI) 1.30 to 1.72) p < 0.0001; number needed to treat = 4.4 (3.3 to 6.6)) without differences in systolic blood pressure (-1.5 mmHg (95% CI -4.0 to 1.0) p = 0.24) or total cholesterol (0.08 mmol/l (95% CI -0.06 to 0.22) p = 0.26). At study end, 17% and 67% of participants in polypill and usual care groups, respectively, were taking atorvastatin or rosuvastatin.
  
  
  CONCLUSIONS
  Provision of a polypill improved self-reported use of indicated preventive treatments. The lack of differences in blood pressure and cholesterol may reflect limited study power, although for cholesterol, improved statin use in the polypill group counter-balanced use of more potent statins with usual care.
authors.affiliation: The George Institute for Global Health, University of Sydney, Australia apatel@georgeinstitute.org.
authors.forename: Anushka
authors.initials: A
authors.lastname: Patel
authors.affiliation: The George Institute for Global Health, University of Sydney, Australia Menzies School of Health Research, Charles Darwin University, Darwin, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Cass
authors.affiliation: The George Institute for Global Health, University of Sydney, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Peiris
authors.affiliation: Department of General Practice, Sydney Medical School (Westmead), The University of Sydney, Australia.
authors.forename: Tim
authors.initials: T
authors.lastname: Usherwood
authors.affiliation: Baker IDI Centre for Indigenous Vascular and Diabetes Research, Alice Springs, Australia South Australian Health and Medical Research Institute, Adelaide, Australia.
authors.forename: Alex
authors.initials: A
authors.lastname: Brown
authors.affiliation: The George Institute for Global Health, University of Sydney, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Jan
authors.affiliation: The George Institute for Global Health, University of Sydney, Australia.
authors.forename: Bruce
authors.initials: B
authors.lastname: Neal
authors.affiliation: The George Institute for Global Health, University of Sydney, Australia.
authors.forename: Graham S
authors.initials: GS
authors.lastname: Hillis
authors.affiliation: National Institute for Health Innovation, School of Population Health, University of Auckland, New Zealand.
authors.forename: Natasha
authors.initials: N
authors.lastname: Rafter
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Tonkin
authors.affiliation: The George Institute for Global Health, University of Sydney, Australia.
authors.forename: Ruth
authors.initials: R
authors.lastname: Webster
authors.affiliation: The George Institute for Global Health, University of Sydney, Australia.
authors.forename: Laurent
authors.initials: L
authors.lastname: Billot
authors.affiliation: The George Institute for Global Health, University of Sydney, Australia.
authors.forename: Severine
authors.initials: S
authors.lastname: Bompoint
authors.affiliation: The George Institute for Global Health, University of Sydney, Australia.
authors.forename: Carol
authors.initials: C
authors.lastname: Burch
authors.affiliation: Maari Ma Aboriginal Corporation, Broken Hill, Australia.
authors.forename: Hugh
authors.initials: H
authors.lastname: Burke
authors.affiliation: Inala Indigenous Health Service, Australia.
authors.forename: Noel
authors.initials: N
authors.lastname: Hayman
authors.affiliation: Baker IDI Centre for Indigenous Vascular and Diabetes Research, Alice Springs, Australia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Molanus
authors.affiliation: Monash Centre of Cardiovascular Research and Education in Therapeutics, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Reid
authors.affiliation: Monash Centre of Cardiovascular Research and Education in Therapeutics, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Louise
authors.initials: L
authors.lastname: Shiel
authors.affiliation: Baker IDI Centre for Indigenous Vascular and Diabetes Research, Alice Springs, Australia.
authors.forename: Samantha
authors.initials: S
authors.lastname: Togni
authors.affiliation: The George Institute for Global Health, University of Sydney, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Rodgers
mesh_terms: D000284:Administration, Oral; D058671:Adrenergic beta-1 Receptor Antagonists / Q000008:administration & dosage; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage; D001262:Atenolol / Q000008:administration & dosage; D001315:Australia; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D004338:Drug Combinations; D016568:Drugs, Generic / Q000008:administration & dosage*; D005260:Female; D058006:General Practice; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D006973:Hypertension / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D017706:Lisinopril / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D019338:Polypharmacy; D011322:Primary Prevention / Q000379:methods*; D011446:Prospective Studies; D012307:Risk Factors; D019821:Simvastatin / Q000008:administration & dosage; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage; D013607:Tablets; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D015415:Biomarkers; D004338:Drug Combinations; D016568:Drugs, Generic; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D049993:Sodium Chloride Symporter Inhibitors; D013607:Tablets; D006852:Hydrochlorothiazide; D001262:Atenolol; D002784:Cholesterol; D019821:Simvastatin; D017706:Lisinopril; D001241:Aspirin
keywords: Cardiovascular disease; adherence; blood pressure; cholesterol; polypill; prevention