What is a Polypill?

Cardiovascular disease is the major cause of mortality worldwide.¹ In recent years, the mortality associated with cardiovascular disease has decreased in developed countries, however, it is rising in developing countries where the use of preventative medication is lower.²

Cardiovascular disease refers to a range of diseases involving the heart and blood vessels. For example, coronary heart disease is a type of cardiovascular disease. Cardiovascular events include adverse incidents related to the cardiovascular system, such as a heart attack.³ Risk factors of cardiovascular disease include high blood pressure and cholesterol levels, and plaque build-up in arteries.⁴

Preventative treatments, such as medications and lifestyle changes, are often prescribed to people at high risk or who have already had a cardiovascular event in order to reduce the risk of future cardiovascular events occurring.⁵

The polypill has been suggested as a preventative treatment for cardiovascular disease that has some benefits over other treatments. So, what is a polypill and what are its benefits?

What is a polypill?

A polypill for cardiovascular disease is a single pill that has a fixed dose of a combination of medications that are often prescribed individually for the prevention of cardiovascular disease.⁶ A polypill can also be used for the prevention of future cardiovascular events in those with established cardiovascular disease.⁷ The medications in the polypill have extensive evidence for their benefits in cardiovascular disease patients.⁶

The polypill is intended to be taken every day. One aim of the polypill is to make it easier for people to stick with taking their medications since more than one medication is present in one pill. This way, people are less likely to have to take more than one type of pill each day.¹

The types and number of medicines in a polypill can differ – there are numerous formulations of the polypill across the world.⁸

Often, a polypill will contain a statin to lower cholesterol levels, a blood pressure-lowering medicine, and an antiplatelet drug to prevent blood clots from forming.⁷ These are all drugs recommended for preventing cardiovascular events in those at high-risk.² They are also associated with a decrease in mortality for people who have cardiovascular disease.¹

History of the polypill

The concept of a single pill containing a combination of drugs dates back to the 1970s. A fixed-dose combination treatment pill was first discussed as a possibility for preventing cardiovascular disease at an expert meeting in 2001.⁵

In 2002, it was proposed to combine aspirin (prevents blood clot formation), statin (lowers cholesterol), ACEI, and beta-blocker – two drugs intended to lower blood pressure – in order to reduce cardiovascular events for patients who have previously had one.²

The term “polypill” came from a publication by Wald and Law (2003), who suggested that polypill use could significantly reduce cardiovascular events. They suggested it be prescribed to anyone over the age of 55, regardless of whether risk factors are present, and to those who have had a cardiovascular event before the age of 55.²

Over the past few decades, many clinical trials have tested the efficacy, safety, and short- and long-term benefits of using polypills. Such research also aims to determine who is the best population for polypill use.     

Who is the polypill intended for?

Primary Prevention

Polypill has been tested for preventing cardiovascular disease in those who have risk factors, such as high blood pressure, but have not yet developed the disease. Primary prevention is often considered for people who are at high risk of developing cardiovascular disease rather than those who are at low or moderate risk, although some studies are testing polypill use in this population.⁵

Secondary Prevention

Secondary prevention aims to prevent a future cardiovascular event, such as a heart attack, from occurring in those who have already had one.⁵ It focuses on reducing the mortality associated with cardiovascular disease in this high-risk population.

Benefits of the polypill

Clinical trials of the polypill have found that keeping up with taking medication is better with the polypill than taking multiple different pills.⁵

Some clinical trials show improvement in systolic blood pressure and cholesterol levels, which are risk factors for developing cardiovascular disease, for those taking the polypill.⁸ In those with established cardiovascular disease, polypill intervention can reduce the risk of future, potentially fatal, cardiovascular events.⁸

Another benefit of polypill treatment is its cost-effective nature, making it valuable for preventing cardiovascular events in at-risk populations in developing countries.²

Negatives of the polypill

The polypill is a fixed-dose combination of medications, making it difficult to adjust the dose of one or a few of the medications in the polypill.¹ It can be more inconvenient to adjust the polypill doses compared to adjusting the dosage of these medicines prescribed individually.

Another consequence of the medicine combination of a polypill is that an adverse side effect of one component may force a person to stop taking the polypill, which includes additional drugs other than the problematic one.¹

Future directions of the polypill

Tackling some of the limitations of the polypill are likely required to increase its uptake around the world. For example, it has been suggested that developing different polypill formulations for specific cardiovascular events or diseases, such as stroke, as well as for high-risk primary prevention would allow the polypill to be more customized to patients’ situations.¹

There is a need for more clinical trials in order to better understand the impact of polypill treatment on deaths associated with cardiovascular disease and its ability to prevent cardiovascular events. Research focusing on low- to moderate-risk populations for primary prevention is also required. The effect of polypill treatment in this particular group needs more research.⁵

References:

1. Roy, A., Naik, N., & Srinath Reddy, K. (2017). Strengths and limitations of using the polypill in cardiovascular prevention. Current Cardiology Reports, 19(5), 45. https://doi.org/10.1007/s11886-017-0853-y
2. López-Jaramillo, P., González-Gómez, S., Zarate-Bernal, D., Serrano, A., Atuesta, L., Clausen, C., Castro-Valencia, C., Camacho-Lopez, P., & Otero, J. (2018). Polypill: An affordable strategy for cardiovascular disease prevention in low-medium-income countries. Therapeutic Advances in Cardiovascular Disease, 12(6), 169–174. https://doi.org/10.1177/1753944718764588
3. Ye, S. (2013) Cardiac Events. In: Gellman M.D., Turner J.R. (eds) Encyclopedia of Behavioral Medicine. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1005-9_1250
4. National Health Service. (2018). Cardiovascular disease. Retrieved from https://www.nhs.uk/conditions/cardiovascular-disease/
5. Webster, R., & Rodgers, A. (2015). Polypill: Progress and challenges to global use—update on the trials and policy implementation. Current Cardiology Reports, 17(12), 1–8. https://doi.org/10.1007/s11886-015-0673-x
6. Muñoz, D., Uzoije, P., Reynolds, C., Miller, R., Walkley, D., Pappalardo, S., Tousey, P., Munro, H., Gonzales, H., Song, W., White, C., Blot, W., & Wang, T. (2019). Polypill for Cardiovascular Disease Prevention in an Underserved Population. The New England Journal of Medicine, 381(12), 1114–1123. https://doi.org/10.1056/NEJMoa1815359
7. Selak, V., & Webster, R. (2018). Polypills for the secondary prevention of cardiovascular disease: Effective in improving adherence but are they safe?. Therapeutic Advances in Drug Safety, 9(2), 157–162. https://doi.org/10.1177/2042098617747836
8. Roshandel, G., Khoshnia, M., Poustchi, H., Hemming, K., Kamangar, F., Gharavi, A., Ostovaneh, M., Nateghi, A., Majed, M., Navabakhsh, B., Merat, S., Pourshams, A., Nalini, M., Malekzadeh, F., Sadeghi, M., Mohammadifard, N., Sarrafzadegan, N., Naemi-Tabiei, M., Fazel, A., … Malekzadeh, R. (2019). Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (Polyiran): A pragmatic, cluster-randomised trial. The Lancet (British Edition), 394(10199), 672–683. https://doi.org/10.1016/S0140-6736(19)31791-X
9. Image by Arek Socha from Pixabay