title: Polypill for the prevention of cardiovascular disease (PolyIran): study design and rationale for a pragmatic cluster randomized controlled trial.
abstract: BACKGROUND
  The complexity of treatment regimens, costs and pill burden decrease the medication adherence and contribute to shortfall in cardiovascular preventive drug coverage. The polypill, a fixed dose combination pill of established drugs, is expected to increase adherence and reduce the costs whilst preventing major cardiovascular events (MCVE).
  
  
  METHODS
  The PolyIran trial is a pragmatic cluster randomized trial nested within the Golestan Cohort Study (GCS). Subjects were randomized to either non-pharmacological preventive interventions alone (minimal care arm) or together with a polypill (polypill arm) comprising hydrochlorothiazide, aspirin, atorvastatin and either enalapril or valsartan. This study benefits from the infrastructure of the primary health care system in Iran and the interventions are delivered by the local auxiliary health workers (Behvarz) to the participants. The primary outcome of the study is the occurrence of first MCVE within five years defined as non-fatal and fatal myocardial infarction, unstable angina, sudden death, heart failure, coronary artery revascularization procedures, and non-fatal and fatal stroke.
  
  
  METHODS
  From February 2011 to April 2013, 8410 individuals (236 clusters) attended the eligibility assessment. Of those, 3421 in the polypill arm and 3417 in the minimal care arm were eligible. The study is ongoing.
  
  
  CONCLUSIONS
  The infrastructure of GCS and the primary health care system in Iran enabled the conduct of this pragmatic large-scale trial. If the polypill strategy proves effective, it may be implemented to prevent cardiovascular disease in developing countries.
authors.affiliation: Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Ostovaneh
authors.affiliation: Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Poustchi
authors.affiliation: School of Health and Population Sciences, University of Birmingham, UK.
authors.forename: Karla
authors.initials: K
authors.lastname: Hemming
authors.affiliation: Golestan Research Center of Gastroenterology and Herpetology, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Hajiamin
authors.initials: H
authors.lastname: Marjani
authors.affiliation: Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Akram
authors.initials: A
authors.lastname: Pourshams
authors.affiliation: Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Nateghi
authors.affiliation: Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Majed
authors.affiliation: Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Navabakhsh
authors.affiliation: Golestan Research Center of Gastroenterology and Herpetology, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Khoshnia
authors.affiliation: Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Jaafari
authors.affiliation: Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Noushin
authors.initials: N
authors.lastname: Mohammadifard
authors.affiliation: Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Malekzadeh
authors.affiliation: Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shahin
authors.initials: S
authors.lastname: Merat
authors.affiliation: Cardiac Rehabilitation Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Sadeghi
authors.affiliation: Golestan Research Center of Gastroenterology and Herpetology, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Naemi
authors.affiliation: Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Arash
authors.initials: A
authors.lastname: Etemadi
authors.affiliation: School of Health and Population Sciences, University of Birmingham, UK.
authors.forename: G Neil
authors.initials: GN
authors.lastname: Thomas
authors.affiliation: Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Nizal
authors.initials: N
authors.lastname: Sarrafzadegan
authors.affiliation: School of Health and Population Sciences, University of Birmingham, UK.
authors.forename: K K
authors.initials: KK
authors.lastname: Cheng
authors.affiliation: School of Health and Population Sciences, University of Birmingham, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Marshall
authors.affiliation: Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran malek@tums.ac.ir.
authors.forename: Reza
authors.initials: R
authors.lastname: Malekzadeh
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001241:Aspirin / Q000008:administration & dosage; D000069059:Atorvastatin / Q000008:administration & dosage; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D002985:Clinical Protocols; D004338:Drug Combinations; D004656:Enalapril / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D007492:Iran; D008297:Male; D008875:Middle Aged; D019338:Polypharmacy; D011322:Primary Prevention / Q000379:methods*; D012107:Research Design; D055502:Secondary Prevention / Q000379:methods*; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D000068756:Valsartan / Q000008:administration & dosage
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002317:Cardiovascular Agents; D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D004656:Enalapril; D000068756:Valsartan; D000069059:Atorvastatin; D001241:Aspirin
keywords: Cardiovascular diseases; polypill; primary prevention; secondary prevention