Jump to: navigation, search


In medicine, the term Polypill has been coined to refer to a medication which contains a combination of active ingredients.

In an important and controversial article in the BMJ in 2003, Wald and Law proposed the concept of a polypill combining 6 medications that are already on the market and have been used for decades in order to reduce cardiovascular disease. Wald and Law used an innovative analytic approach that combined the numerical results from several high quality meta-analyses of the individual impact of these medications to produce an estimate of the overall combined effect of the proposed polypill on morbidity and mortality.

So, the "polypill" is both

  1. an idea for a physical pill - to increase adherence / compliance by reducing the number of pills that a person has to take, and
  2. a novel methodological approach - in a sense a numeric "meta-analysis of meta-analyses" to estimate the combined impact of several medications and / or interventions.

Since then, there have been many articles written proposing other sorts of "polypills", and using methodology similar to Wald and Law's.

One of the most promising is a "polypill" for diabetes (and potentially for pre-diabetes). (See : Kuehn B. M. 2006. ""Polypill" Could Slash Diabetes Risks" JAMA. 2006;296:377-380.)

Wald and Law's "Polypill" Strategy to Reduce Cardiovascular disease by more than 80 %

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 - calculated from the overwhelming evidence in favor of the polypill's individual components. The concepts they present are well recognised: reducing blood pressure, cholesterol and taking a low dose of aspirin will help prevent heart disease and stroke. Tests of the Wald and Law polypill have been recommended in 2005. Additionally, "polypills" are currently available in India. Any GP can currently prescribe the ALL the components of the polypill separately for her/his patients. Unfortunately, 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).

Wald and Law has taken the unusual and novel perspective that everyone over the age of 55 should take a pill containing medications to manage these issues irrespective of individual risks. The idea is that if you reduce all blood pressures and cholesterols in all patients the population will benefit. 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 50 year longitudinal study (and still going) 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 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”.

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-inflamatory properties.
  2. An ACE inhibitor (for blood pressure control AND to protect the kidneys).
  3. Aspirin (antiplatelet and antiinflamatory 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

If Wald and Law's analysis is correct, major cost savings and productivity gains can be obtained from a polypill approach. Similarly, the Diabetes / Syndrome X polypill is estimated to save 100s of billions of dollars.

More importantly, the tremendous human cost of these devastating and underappreciated 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 carers. Kidney failure and dialysis (common in end-stage diabetics) is also devastating.

A health care system or major insurer - like Kaiser Permanente - could do very well both financially and on a human level - if they fully tested and introduced the polypills.

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 are 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 low fat diet, that over time you can dramatically reduce your cardiovascular risk.

Unfortunately, most people - in reality - find this far too difficult, unpleasant, invasive and intrusive to adhere to, and therefore can not - in reality - achieve and sustain these gains.

Furthermore, there is increasing evidence that even among individuals with healthly lifestyles, that 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 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 article - which is quite well written - proposes - with tongue in cheek - a mixture of many different healthy food types. The authors have referred to this as the polymeal.


Wald and Law. 2003. A strategy to reduce cardiovascular disease by more than 80% British Medical Journal on June 28, 2003.

Kuehn B. M. 2006. ""Polypill" Could Slash Diabetes Risks" JAMA. 2006;296:377-380.