PolyPill for Prevention of Cardiovascular Disease in an Urban Iranian Population with Special Focus on Nonalcoholic Steatohepatitis: A Pragmatic Randomized Controlled Trial within a Cohort (PolyIran - Liver) - Study Protocol.
BACKGROUND
Cardiovascular disease (CVD) is among the most common causes of mortality in all populations. Nonalcoholic steatohepatitis is a common finding in patients with CVD. Prevention of CVD in individual patients typically requires periodic clinical evaluation, as well as diagnosis and management of risk factors such as hypertension and hyperlipidemia. However, this is resource consuming and hard to implement, especially in developing countries. We designed a study to investigate the effects of a simpler strategy: a fixed-dose combination pill consisting of aspirin, valsartan, atorvastatin and hydrochlorthiazide (PolyPill) in an unselected group of persons aged over 50 years.


METHODS
The PolyIran-Liver study was performed in Gonbad city as an open label pragmatic randomized controlled trial nested within the Golestan Cohort Study. We randomly selected 2,400 cohort study participants aged above 50 years, randomly assigned them to intervention or usual care and invited them to participate in an additional measurement study (if they met the eligibility criteria) to measure liver related outcomes. Those agreeing and randomized to the intervention arm were offered a daily single dose of PolyPill. We will follow participants for 5 years. The primary outcome is major cardiovascular events, secondary outcomes include all-cause mortality and liver related outcomes: liver stiffness and liver enzyme levels. Cardiovascular outcomes and mortality will be determined from the cohort study and liver-related outcomes in those consenting to follow up. Analysis will be by allocated group.


METHODS
Between October and December 2011, 1,320 intervention and 1,080 control participants were invited to participate in the additional measurement study. For all these participants, the major cardiovascular events will be determined using blind assessment of outcomes through the cohort study. In the intervention and control arms, 875 (66%) and 721 (67%) respectively, met the eligibility criteria and agreed to participate in the additional measurement study. Liver related outcomes will be measured in these participants. Of the 1,320 participants randomized to the intervention, 787 (60%) accepted the PolyPill.


CONCLUSIONS
The PolyIran-liver urban study will provide us with important information on the effectiveness of PolyPill on major cardiovascular events, all-cause mortality and liver related outcomes. (ClinicalTrials.gov ID: NCT01245608).
1)Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.2)Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Shahin
S
Merat
1)Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.2)Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Hossein
H
Poustchi
School of Health and Population Sciences, University of Birmingham, Birmingham, U.K.
Karla
K
Hemming
1)Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran. 4)Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Elham
E
Jafari
Department of Radiology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Amir-Reza
AR
Radmard
Research and Development Department, Alborz-Darou Pharmaceutical Co., Ghazvin, Iran.
Alireza
A
Nateghi
Department of Radiology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Abolfazl
A
Shiravi Khuzani
Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran.
Masoud
M
Khoshnia
School of Health and Population Sciences, University of Birmingham, Birmingham, U.K.
Tom
T
Marshall
1)Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran. 2)Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.4)Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Reza
R
Malekzadeh
D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D001241:Aspirin / Q000008:administration & dosage; D000069059:Atorvastatin / Q000008:administration & dosage; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D004232:Diuretics / Q000008:administration & dosage; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D007492:Iran; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D014505:Urban Population; D000068756:Valsartan / Q000008:administration & dosage
D047228:Angiotensin II Type 1 Receptor Blockers; D004232:Diuretics; D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D006852:Hydrochlorothiazide; D000068756:Valsartan; D000069059:Atorvastatin; D001241:Aspirin