Our analysis shows that a Polypill Prevention Programme in which people aged 50 and over are offered a daily polypill would be effective in the prevention of MI and stroke. In our working case approximately one million years of life without a first MI or stroke in the UK would be gained every year. There are few public health programmes that could deliver such great gains in reducing morbidity and mortality in many countries throughout the world.
The cost of a mature Polypill Prevention Programme per year of life gained without a first MI or stroke would be approximately £2000 if the cost of providing the polypill were £1 per day per person and, in the working case, £2 billion annually for the UK as a whole (approximately 1.5 % of UK Public Sector Health Expenditure in 2014 ). Our analysis uses the concept of “years of life gained without a first MI or stroke” instead of simply “years of life gained”, because our focus is the prevention of non-fatal and fatal events. In some instances years of life gained may be the preferred measure of health benefit. An example is breast cancer screening where the method of prevention is early cancer detection and its treatment, in which years of life gained without being aware of breast cancer would be reduced. However in the primary prevention of a disorder that causes early death and morbidity, the preferred measure is life years gained without the disorder. Also, we deliberately did not adopt an adjusted measure known as “quality adjusted life years” or “QALYs”. Any adjustment due to disability arising from an MI or stroke would not be relevant in our analysis because we estimated years of life gained without either of these events. In any event, if we had estimated total life years gained, we would have been reluctant to use any adjustments which imply that the life of a disabled individual is of less value than that of a similar individual living without disability. It is increasingly recognised that the quality of life is a personal matter, and not one where the State or other agencies should impose their judgement [18, 19]. Notwithstanding these considerations, a cost of £2000 per year of life gained without a first MI or stroke is amply cost-effective in relation to the conventionally accepted maximum cost figure of between £20,000 and £30,000 per quality adjusted year of life gained allowed by NICE .
Our analysis combines data on males and females. The age-specific incidences being less in females, the cost per year of life gained without an MI or stroke is about £1000 more in females than males if the cost of delivering a polypill service is £1 per person per day. If the costs were set to be the same in both sexes the female cut-off would be about 10 years later (age 60) but, on average, women would lose about 8 months of extra life without an MI or stroke. The sex-specific policy trade-offs are finely balanced and do not justify separate age cut-offs for males and females .
The sensitivity analyses indicate that our estimates are robust to variations in the factors considered (Tables 4 and 5). For example, it is likely that a Polypill Prevention Programme will be taken up more readily among people in higher socio-economic groups. This will have only a modest effect on our estimates; even if the MI and stroke incidence were three times as great in lower socio-economic groups than in higher, and if twice as many people in higher socio-economic groups were to take up the polypill, the incidence of these disorders would be about 10 % lower in people taking the polypill than in the population as a whole, well within the limits of our sensitivity analysis on incidence.
Our results are not influenced by secondary prevention services because our paper is limited to the prevention of first events. The estimates are based on introducing a Polypill Prevention Programme in a population not receiving medication for primary prevention. At present in England there is a primary prevention programme provided by the National Health Service called “Health Checks” that involves adopting a Framingham-type screening approach. Although it might be argued that the polypill approach should be directly compared with this approach, there is both a scientific and a practical reason not to do so. The scientific reason is that provided the cost of a Polypill Prevention Programme is not excessive, it would be more cost effective, as shown in an earlier analysis comparing age screening with screening using multi-factor risk scores . The practical reason is that the English Health Check programme lacks specificity and clarity over the interventions offered, and over the effect of these interventions in reducing morbidity and mortality, thereby making it impossible reliably to assess costs and benefits. The Polypill Programme overcomes these weaknesses and should be assessed independently of any other intervention.
The effect of a Polypill Prevention Programme on the total years of life gained without a first MI or stroke in the UK will depend on the size of the progressive annual cohorts of people aged 50, which can vary by up to 15 % from year to year. As a result, the total of such years gained is unlikely to fall below 850,000. This variation in the 50-year-olds cohort size does not, however, affect the cost per year gained, because as less people take up the polypill, the benefits and costs decline together almost pro rata.
The years of life gained without a first MI or stroke decline with increasing age of starting. For example, starting at age 55 instead of 50 in the working model, the gain in years of life without a first MI or stroke is reduced by about 10 % (910,000 instead of 990,000). At the same time, the net cost is reduced by about 30 % (£1.50 bn instead of £2.11 bn) and the cost per year of life gained without a first MI or stroke is reduced by about 20 % (£1650 instead of £2120). The disadvantage in setting a higher age cut-off, of course, is the failure to prevent MIs and strokes in younger people, and a reduction in overall public health benefit.
Reducing LDL cholesterol and blood pressure will prevent cardiovascular diseases other than MI and stroke, such as angina pectoris and aortic aneurysm. The Polypill Prevention Programme may also have a beneficial effect in preventing arteriosclerotic dementia. There is evidence that use of the polypill will reduce the prevalence of headaches by approximately one-third . Most of the side effects of the polypill relate to intolerance and are not serious. This will result in some people deciding to stop taking it (in our example 17 %). The main serious side effect is rhabdomyolysis, arising from the use of statins, with an estimated risk of approximately 3 per 100,000 persons per year, and mortality of approximately 0.3 per 100,000 persons per year . This estimate is consistent with the observation that in 2013 in England and Wales 7.6 million people took statins [25, 26] and 86 deaths were recorded as being due to rhabdomyolysis (ICD-10, M62.8) , of which about 20 would have been statin related. Statins increase the incidence of diabetes by an estimated 9 % but it is good practice to prescribe, in such cases, the components in the polypill, as the benefit far outweighs the risks .
Discounting the value of future health benefits and financial cost/saving in economic analyses of public health programmes is debatable [18, 29, 30], but it is irrelevant to our analysis. Once the programme is mature, there is a steady state between annual costs and benefits, both being constant from year to year, thus dispelling any possible rationale for discounting.
A challenge in introducing an NHS Polypill Prevention Programme will be to secure professional and public acceptance that the focus should be on providing effective and safe preventive treatment, rather than paying more attention to screening measurements . Such measurements add little beyond the use of age to the prediction of cardiovascular disease. They do, however, add significantly to the workload of medical staff, arising from the associated extra medical consultations, laboratory tests, implementation of screening algorithms and risk counselling. Many doctors may feel that an individual should receive cholesterol lowering treatment only if the LDL cholesterol is raised or blood pressure lowering treatment only if his or her blood pressure is raised above essentially arbitrary cut-off values. This however means that some people at risk do not receive preventive treatment and others receive only some of the components in the polypill, when using all of them confers greater efficacy. Preventive treatment should involve reducing both LDL cholesterol and blood pressure, regardless of pre-treatment levels, because the benefit of doing so is not limited to people with high levels [16, 31, 32].
If everyone aged 50 and over in the UK were invited to join a Polypill Prevention Programme in 1 year, approximately 22 million people would be invited, representing about 2300 per GP practice in year one, and about a hundred in each year thereafter. If recruiting 2300 people in a single year poses too heavy an administrative burden on each practice (about 45 per week), recruitment could be phased over 2 years. That would mean about 1200 invitations per year in the first 2 years (about 22 per week) and about 100 per year thereafter. Perhaps more importantly, once a Polypill Prevention Programme were underway, there would be only about 100 new invitations each year per practice.
General Practice surgeries would identify people on their list when they reach their 50th birthday, write to them to determine contraindications to preventive cardiovascular disease treatment (such as certain pre-existing diseases or medications which each person would indicate in a response to a short list of questions) and, if eligible, offer them a polypill to diminish the likelihood of future MIs and strokes. Acceptance could be done by mail or email and a prescription sent to a pharmacy for dispensing. The polypill could be sent to each polypill participant by post, or could be collected from a designated local pharmacy. The process could be implemented and monitored in a largely automated way, releasing General Practitioner time and resources for patients with medical problems.
Identifying people by age as being eligible for a polypill avoids them feeling that they are patients or being regarded as patients. They do not have a medical disorder that needs treatment; they choose to take a preventive medication to avoid becoming a patient. The UK National Health Service (NHS) and other collectively funded health care systems such as US Health Maintenance Organizations are ideal settings in which to implement the polypill concept.
Others who have conducted cost-effectiveness analyses, adopting different screening strategies and different estimates of cost, have concluded that cardiovascular disease prevention with a polypill is cost-effective, across a range of estimates of drug efficacy and treatment cost [33–35]. For example, an Australian study  ranked a polypill strategy as one of the most cost-effective interventions in the prevention of cardiovascular disease. Another study assessed an age-based screening strategy in low and middle income countries using an age cut-off of 55 years as being cost-effective . In 2014 the US Rand Corporation conducted a case-study of “A Cardiovascular Polypill”  and again found it to be cost-effective .
Our analysis adds to the information available from previous economic analyses of the polypill. It focuses on three important measures relevant to assessing the merits of a National Polypill Prevention Programme: net cost for a total programme, years of life gained without a first MI or stroke, and net cost per year of life gained without a first MI or stroke. These estimates are here applied to the UK as a whole, to guide the National Health Service and other similarly managed health care services to develop policy in this area. The NHS could introduce a Polypill Prevention Programme generally or conduct a prior demonstration project in a large sample of GP practices within the UK, and audit the project.
From the perspective of each individual, and that of society as a whole, a Polypill Prevention Programme offers considerable health benefits at a relatively low cost.