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Effectiveness of Polypill for Primary and Secondary Prevention of Cardiovascular Diseases: A Pragmatic Cluster Randomized Controlled Trial

50 Pages Posted: 24 Jun 2019

See all articles by Gholamreza Roshandel

Gholamreza Roshandel

Tehran University of Medical Sciences - Digestive Disease Research Center

Masoud Khoshnia

Tehran University of Medical Sciences - Digestive Disease Research Center

Hossein Poustchi

Tehran University of Medical Sciences

Karla Hemming

University of Birmingham

Farin Kamangar

Morgan State University

Abdolsamad Gharavi

Tehran University of Medical Sciences - Digestive Disease Research Center

Mohammadreza Ostovaneh

Tehran University of Medical Sciences - Digestive Disease Research Center

Alireza Nateghi

Tehran University of Medical Sciences - Digestive Disease Research Center

Masoud Majed

Tehran University of Medical Sciences - Digestive Disease Research Center

Behrooz Navabakhsh

Tehran University of Medical Sciences - Digestive Disease Research Center

Shahin Merat

Tehran University of Medical Sciences - Digestive Disease Research Institute

Akram Pourshams

Tehran University of Medical Sciences - Digestive Disease Research Center

Mahdi Nalini

Tehran University of Medical Sciences - Digestive Disease Research Center

Fatemeh Malekzadeh

Tehran University of Medical Sciences - Digestive Disease Research Center

Masoumeh Sadeghi

Isfahan University of Medical Sciences

Noushin Mohammadifard

Isfahan University of Medical Sciences

Nizal Sarrafzadegan

Isfahan University of Medical Sciences

Mohammad Naemi-Tabiei

Golestan University of Medical Sciences

Abdolreza Fazel

Golestan University of Medical Sciences

Paul Brennan

World Health Organization

Arash Etemadi

Government of the United States of America - Division of Cancer Epidemiology and Genetics

Paolo Boffetta

Mount Sinai Health System - Icahn School of Medicine

Neil Thomas

University of Birmingham - Institute of Applied Health Research

Tom Marshall

University of Birmingham - Institute of Applied Health Research

Kar Keung Cheng

University of Birmingham - Institute of Applied Health Research

Reza Malekzadeh

Tehran University of Medical Sciences - Digestive Disease Research Center; Digestive Oncology Research Center; Liver and Pancreaticobiliary Disease Research Center

More...

Abstract

Background: A fixed-dose combination therapy ("polypill" strategy) has been proposed as an approach to reduce the burden of cardiovascular disease (CVD), especially in lower resource settings. We conducted the PolyIran Study to assess the effectiveness and safety of a four-component polypill including aspirin, atorvastatin, hydrochlorothiazide and either enalapril or valsartan, for primary and secondary prevention of CVD.

Methods: The study population comprised of rural participants of the Golestan Cohort Study aged 50 years or older. Considering villages as clusters, the study participants were cluster randomized to a package of non-pharmacological preventive interventions either alone (minimal care arm) or together with a once daily polypill (polypill arm). Participants were followed for 60 months. The primary outcome was occurrence of major cardiovascular events (MCVE), which was compared between the two arms using Cox regression models with shared frailty.

Findings: Overall, 6838 individuals were enrolled in the study, including 3417 (in 116 clusters) in the minimal care arm and 3421 (in 120 clusters) in the polypill arm. Median (interquartile range) adherence to polypill tablets was 80.5% (48.5%-92.2%). During the follow up, 202 and 301 participants in the polypill and minimal care arms, respectively, had one or more MCVE (adjusted hazard ratio [HR]=0.66; 95% confidence interval [CI]: 0.55-0.80). Polypill was effective for both primary and secondary prevention of CVD. When restricted to participants with high adherence, the risk of MCVE was further reduced (adjusted HR=0.43; 95%CI: 0.33-0.55). Overall, the frequency of adverse events was comparable between the two arms.

Interpretation: Using polypill was effective in preventing MCVE. Medication adherence was high, and rates of adverse events were low. The polypill strategy may be considered as an additional effective component in controlling CVDs, especially in low resources settings.

Trial Registration: Cllinicaltrials.gov identifier: NCT01271985.

Funding Statement: The study was supported by and Alborz Darou, Barakat Foundation, and Tehran University of Medical Sciences. Golestan Cohort study was supported by Cancer Research UK (grant number: C20/A5860), Tehran University of Medical Sciences (grant number: 81/15), and the International Agency for Research on Cancer.

Declaration of Interests: The authors disclose no conflicts.

Ethics Approval Statement: The protocol of the PolyIran Study was reviewed and approved by Institutional Review Board (IRB) of Digestive Diseases Research Institute and Tehran University of Medical Sciences.

Suggested Citation

Roshandel, Gholamreza and Khoshnia, Masoud and Poustchi, Hossein and Hemming, Karla and Kamangar, Farin and Gharavi, Abdolsamad and Ostovaneh, Mohammadreza and Nateghi, Alireza and Majed, Masoud and Navabakhsh, Behrooz and Merat, Shahin and Pourshams, Akram and Nalini, Mahdi and Malekzadeh, Fatemeh and Sadeghi, Masoumeh and Mohammadifard, Noushin and Sarrafzadegan, Nizal and Naemi-Tabiei, Mohammad and Fazel, Abdolreza and Brennan, Paul and Etemadi, Arash and Boffetta, Paolo and Thomas, Neil and Marshall, Tom and Cheng, Kar Keung and Malekzadeh, Reza, Effectiveness of Polypill for Primary and Secondary Prevention of Cardiovascular Diseases: A Pragmatic Cluster Randomized Controlled Trial (June 21, 2019). Available at SSRN: https://ssrn.com/abstract=3408063

Gholamreza Roshandel

Tehran University of Medical Sciences - Digestive Disease Research Center

Iran

Masoud Khoshnia

Tehran University of Medical Sciences - Digestive Disease Research Center

Iran

Hossein Poustchi

Tehran University of Medical Sciences

Number 21, Dameshg St.
Vali-e Asr Ave.
Tehran, 14195
Iran

Karla Hemming

University of Birmingham

Department of Civil Engineering
Edgbaston, VT Birmingham B15 2TT
United Kingdom

Farin Kamangar

Morgan State University

1700 E. Cold Spring Ln
Baltimore, MD 21251
United States

Abdolsamad Gharavi

Tehran University of Medical Sciences - Digestive Disease Research Center

Iran

Mohammadreza Ostovaneh

Tehran University of Medical Sciences - Digestive Disease Research Center

Iran

Alireza Nateghi

Tehran University of Medical Sciences - Digestive Disease Research Center

Iran

Masoud Majed

Tehran University of Medical Sciences - Digestive Disease Research Center

Iran

Behrooz Navabakhsh

Tehran University of Medical Sciences - Digestive Disease Research Center

Iran

Shahin Merat

Tehran University of Medical Sciences - Digestive Disease Research Institute ( email )

Number 21, Dameshg St.
Vali-e Asr Ave.
Tehran, 14195
Iran

Akram Pourshams

Tehran University of Medical Sciences - Digestive Disease Research Center

Iran

Mahdi Nalini

Tehran University of Medical Sciences - Digestive Disease Research Center

Iran

Fatemeh Malekzadeh

Tehran University of Medical Sciences - Digestive Disease Research Center

Iran

Masoumeh Sadeghi

Isfahan University of Medical Sciences

Hezar Jerib Avenue
Isfahan, 81745
Iran

Noushin Mohammadifard

Isfahan University of Medical Sciences

Hezar Jerib Avenue
Isfahan, 81745
Iran

Nizal Sarrafzadegan

Isfahan University of Medical Sciences

Hezar Jerib Avenue
Isfahan, 81745
Iran

Mohammad Naemi-Tabiei

Golestan University of Medical Sciences

Gorgan, Golestan
Iran

Abdolreza Fazel

Golestan University of Medical Sciences

Gorgan, Golestan
Iran

Paul Brennan

World Health Organization

20 Avenue Appia
Geneva 27, CH-1211
Switzerland

Arash Etemadi

Government of the United States of America - Division of Cancer Epidemiology and Genetics

Bethesda, MD 20892
United States

Paolo Boffetta

Mount Sinai Health System - Icahn School of Medicine

One Gustave L. Levy Place
New York, NY 10029-6574
United States

Neil Thomas

University of Birmingham - Institute of Applied Health Research

Birmingham, B15 2TT
United Kingdom

Tom Marshall

University of Birmingham - Institute of Applied Health Research

Birmingham, B15 2TT
United Kingdom

Kar Keung Cheng

University of Birmingham - Institute of Applied Health Research

Birmingham, B15 2TT
United Kingdom

Reza Malekzadeh (Contact Author)

Tehran University of Medical Sciences - Digestive Disease Research Center ( email )

Iran

Digestive Oncology Research Center ( email )

Iran

Liver and Pancreaticobiliary Disease Research Center ( email )

Iran

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