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A polypill is a medication which contains a combination of active ingredients with the intention of reducing the number of tablets or capsules that need to be taken.



The broad concept of a polypill for cardiovascular disease has existed for decades, with early proponents coining the term "aspolol" i.e. a combination of aspirin and atenolol. Fixed dose combinations are common in other clinical areas, such as tuberculosis and HIV/AIDS. The Wellcome Trust and World Health Organisation convened a meeting to discuss the concept in 2001 [1], but did not progress it at that time. The concept was mentioned by Dr. Salim Yusuf in an editorial in The Lancet in 2002.[2]

In a 2003 article in the BMJ, Wald and Law coined the term "polypill" and proposed the concept of combining six medications that have been used for decades to treat cardiovascular disease and providing this to all people with cardiovascular disease and those in Western countries aged 55 years or more. They combined the numerical results from several meta-analyses of the individual effects of these medications to produce an estimate of the overall combined effect on morbidity and mortality.

Articles using similar methods have proposed other sorts of polypills, including one for diabetes (and potentially for pre-diabetes).[3]

Cardiovascular polypill

In their paper A strategy to reduce cardiovascular disease by more than 80% (published in the British Medical Journal) on June 28, 2003, Wald and Law postulated that by using a combination of well known, cheap medications in one pill (the "Polypill") would be a particularly effective treatment against cardiovascular disease. They presented a statistical model which suggested widespread use of the polypill could reduce mortality due to heart disease and strokes by up to 80%. The treatment is potentially cheap, with few side effects (in perhaps 10-15% of recipients) and the research was based on data from many trials relating to the individual components.

To date there have, however, been no actual patient research on the real benefits of the combined medications compared to the inferred benefits which were calculated from the evidence in favor of the polypill's individual components. The concepts they present are based on these principles: reducing blood pressure, cholesterol and taking a low dose of aspirin to help prevent heart disease and stroke.(In the interim, however, there is concern that the use of aspirin in a healthy population causes more harm than good.[4]) Tests of the Wald and Law polypill have been recommended in 2005. Additionally, "polypills" are currently available in India. Any GP can currently prescribe all the components of the polypill separately for her/his patients. The ingredients of the polypill are off patent. Since this would make the polypill quite cheap (some estimates on the BMJ rapid responses were less than 70 pounds per year), there is little financial incentive for pharmaceutical companies to pay the high costs of a clinical trial. (Naturally, however, large insurers, or national healthcare systems, may have considerable financial incentive to pay for such trials).

Cardiologists in Spain (Sanz and Fuster, 2009) are currently developing a polypill for secondary cardiovascular prevention. This project is being done in collaboration with Ferrer-Internacional, which is a Spanish pharmaceutical company based in Barcelona with experience in the development and launching of international projects.These authors believe that this polypill delivered at a low price could improve adherence to treatment, reduce the cost and make treatment affordable in low-income countries. Furthermore, they preview that success in this area of prevention could lead to the development of polypills for several other diseases, such as diabetes and stroke.

Treatment of population risk

Wald and Law has taken the novel perspective that everyone over the age of 55 should take a pill containing medications to manage these issues irrespective of individual risk factor levels. The idea is that most people in Western Countries are at high overall risk, and the lowering risk factor levels will benefit all. Central to this is the realisation that risk factors are continuously associated with risk, and the dichotomies of, for example, "hypertension" and "no hypertension" have no scientific basis.[5] Basically, the polypill could be used as a default medication for all people over 55 (or for others with comparable risks).

Currently, individual cardiovascular risk can be calculated based on the 50-year (and still going) longitudinal study on the population of Framingham, Massachusetts (the Framingham Heart Study). The polypill takes a population-based approach to management. The concept of "normal" and treatment thresholds becomes less relevant when taking a population-based approach to disease control. Traditionally, the approach has been to treat only if certain risk thresholds have been reached.

Paradoxically, even though an individual maybe not reach these traditional thresholds, benefit will still accrue by further reductions in blood pressure, cholesterol etc. This is because there is a sliding scale of risk; the concept of abnormal on one side of the line corresponding to high risk and requiring treatment, and normal on the other side, being low risk requiring no treatment is now under scrutiny.

Doctors will be treating population risk rather than individual risk factor thresholds as is current mainstream practice. So, if everyone was given the “Polypill” the average blood pressure and cholesterol levels within the population would fall, thus reducing overall population risk.

The "polypill" would contain 3 blood pressure medications at low dose:

This is combined with

Folic acid has been shown to reduce the level of homocysteine in the blood which is another risk factor for heart disease.

Further research is being planned and coordinated after an international forum recently discussed the concept of the “Polypill”.

The Indian Polycap Study

A study called The Indian Polycap Study (TIPS) was sponsored by Cadila Pharmaceuticals Limited and led by Dr. Salim Yusuf of McMaster University in Hamilton, Ontario, and Dr. Prem Pais of St. John's Medical College in Bangalore, India. The results of the randomized, controlled, double-blind study, reported in March 2009 at an American College of Cardiology conference and published online by The Lancet, documented the outcome of 2,000 individuals with an average age of 54 given the medication, all of whom had at least one heart disease risk factor: diabetes, hypercholesterolemia, hypertension, obesity or smoking.

During a 12-week treatment period, 400 of the study participants were given Polycap. The remainder were divided into eight groups of 200 who were given either individual components or groups of them.[1] Three of the groups of 200 received only aspirin, simvastatin or thiazide respectively; Three groups received two of the three blood pressure medications; Another received all three blood pressure medications, while the last received all three combined with aspirin.

The individuals who were given Polycap saw their blood pressure drop from six to seven points for both their systolic and diastolic levels. These reductions in blood pressure could cut the risk of heart disease by 62% and of stroke by 48% based on the results of other studies that showed risk reductions from cutting blood pressure levels. The combined pill was almost as effective as the individual pills with no increase in side effects.

Polypill for diabetes and Syndrome X

Diabetes - particularly Type II diabetes is a major cause of morbidity and mortality. Diabetes also contributes substantially to cardiovascular risk. Unfortunately, some of the ingredients in Wald and Law's original polypill may not be advisable for patients with diabetes (for example : beta-blockers - which can lead to weight gain, and thiazide diuretics). The polypill for diabetes includes :

  1. A Statin. To reduce LDL cholesterol and they also have recently been shown to have anti-inflammatory properties.
  2. An ACE inhibitor (for blood pressure control AND to protect the kidneys).
  3. Aspirin (antiplatelet and anti-inflammatory properties), and
  4. Metformin - an excellent medication for diabetes that is also associated with weight loss.

Many people who are overweight are diabetic without knowing it. Many additional people have pre diabetes and may benefit from active intervention. Overall, people who have diabetes or prediabetes, high cholesterol and /or high blood pressure and are overweight are considered to have metabolic syndrome X, and may benefit substantially from the Diabetes polypill.

Perhaps, as the polypill strategy becomes widely adopted, people over 55 with a "normal" body mass index or waist circumference will take the Wald and Law polypill, and the obese or substantially overweight will take the Diabetes / Syndrome X polypill.

Cost effectiveness

Wald and Law's analysis predicts major cost savings and productivity gains can be from a polypill approach. Similarly, the Diabetes / Syndrome X polypill is estimated to save hundreds of billions of dollars.

More importantly, the human cost of these chronic diseases can be substantially reduced. When a person has a stroke, it can ruin his or her quality of life. It also places a major burden on careers. Kidney failure and dialysis (common in end-stage diabetics) is also devastating.

Sources of resistance

Medical expertise and simplicity of treatment

If a polypill strategy works for a large percentage of the patient population, it may threaten some experts and specialists who might stand to lose financially (although no doubt most of these experts would be delighted by the human benefits, and would probably endorse it - despite any personal financial hardship that this might cause them).

The polypill, being a simple "off-the-rack" default treatment, also reduces the sense of control and exercise of expertise that comes from prescribing individually tailored medication regimens. Unfortunately, individually tailored approaches may be more expensive and difficult and time consuming to access.

Lifestyle Modification and "punishing the sinners"

There is a large cohort of health professionals that advocate lifestyle modification. It is true that, if you stop smoking, exercise an hour or more a day, and eat a healthy diet, over time you can dramatically reduce your cardiovascular risk.

A counter-argument to this is that most people find this regimen too difficult, unpleasant, invasive and intrusive to adhere to, and therefore cannot achieve and sustain these gains.

Furthermore, there is increasing evidence that even among individuals with healthy lifestyles, some medications, like statins, can even further reduce one's cardiovascular risk.

It is, no doubt, best to remind patients about the benefits of lifestyle modifications and encourage them to pursue them, but proponents of polypills argue that this does not justify delay of potentially highly beneficial medications like the polypill. In practice, most people above 55 will not be able to sustain sufficient lifestyle modifications, and will benefit from medications such as those contained in the polypill.

In a sense, overly strong devotion to the lifestyle modification approach implies that "sinners" (those who are unable or unwilling to dramatically alter their lifestyle and habits) should expect to suffer for their non-compliance. This does not seem to be an appropriate way to deal with our fellow human beings who, like ourselves, are sometimes flawed and weak but nevertheless deserve effective preventive care.

Naturally, individuals who prefer to first try a lifestyle modification approach should be encouraged to do so. But they should also be reminded that many people do not succeed and that effective medical treatment is available.

Cardiovascular disease and diabetes are often asymptomatic until substantial irreversible damage has been done. This makes a dogmatic "lifestyle modification" approach particularly dangerous because it may drive away patients from treatment.


Wald and Law's approach has generated substantial controversy and criticism. Some of the more original contributions in this regard have take the form of satire. One such facetious article proposes that consumption of a mixture of many different healthy food types, mainly a Mediterranean diet and Red Wine will have similar benefits as the Polypill. The authors have referred to this as the polymeal. The BMJ even ran a Polymeal contest inviting people to come up with a meal using the 6 ingredients.


  • Fuster V, Sanz G (April 2007). [Expression error: Missing operand for > "A polypill for secondary prevention: time to move from intellectual debate to action"]. Nat Clin Pract Cardiovasc Med 4 (4): 173. doi:10.1038/ncpcardio0858. PMID 17380163. 
  • Sanz G, Fuster V (February 2009). [Expression error: Missing operand for > "Fixed-dose combination therapy and secondary cardiovascular prevention: rationale, selection of drugs and target population"]. Nat Clin Pract Cardiovasc Med 6 (2): 101–10. doi:10.1038/ncpcardio1419. PMID 19104519. 
  • Xavier D, Pais P, Sigamani A, Pogue J, Afzal R, Yusuf S (February 2009). [Expression error: Missing operand for > "The need to test the theories behind the Polypill: rationale behind the Indian Polycap Study"]. Nat Clin Pract Cardiovasc Med 6 (2): 96–7. doi:10.1038/ncpcardio1438. PMID 19104516. 
  • Yusuf S, Pais P, Afzal R, et al. (April 2009). [Expression error: Missing operand for > "Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): a phase II, double-blind, randomised trial"]. Lancet 373 (9672): 1341–51. doi:10.1016/S0140-6736(09)60611-5. PMID 19339045. 
  • Gorman, Rachael Moeller. "The Polypill" Proto, Winter 2007


  1. . World Health Organization. Secondary prevention of non-communicable disease in low and middle income countries through community-based and health service interventions. World Health Organization - Wellcome Trust meeting report 1–3 August 2001, Geneva. 2002
  2. Yusuf S (July 2002). [Expression error: Missing operand for > "Two decades of progress in preventing vascular disease"]. Lancet 360 (9326): 2–3. doi:10.1016/S0140-6736(02)09358-3. PMID 12114031. 
  3. Kuehn BM (July 2006). [Expression error: Missing operand for > ""Polypill" could slash diabetes risks"]. JAMA 296 (4): 377–80. doi:10.1001/jama.296.4.377. PMID 16868284. 
  4. Smith R (August 30, 2009). "Aspirin does more harm than good in healthy people: research". http://www.telegraph.co.uk/health/healthnews/6114302/Aspirin-does-more-harm-than-good-in-healthy-people-research.html. 
  5. Law MR, Wald NJ (June 2002). [Expression error: Missing operand for > "Risk factor thresholds: their existence under scrutiny"]. BMJ 324 (7353): 1570–6. doi:10.1136/bmj.324.7353.1570. PMID 12089098. 
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