Primary prevention of heart attacks and strokes: seeking consensus on the polypill approach
BMJ 2025; 388 doi: https://doi.org/10.1136/bmj.r208 (Published 05 March 2025) Cite this as: BMJ 2025;388:r208
Heart attacks and strokes rise exponentially with age and make a major contribution to increasing healthcare costs and lost productivity. In the UK more than 7 million people are living with cardiovascular disease. Around 100 000 people have a heart attack and more than 100 000 people have a stroke every year. Direct healthcare costs relating to cardiovascular disease are estimated at £10bn a year, with a cost of £25bn to the UK economy from lost productivity.1
Preventive medication to reduce blood pressure and low density lipoprotein (LDL) cholesterol can have a major effect in avoiding most cases of heart attack and stroke.23 This opportunity has been neglected and should form part of an overall preventive strategy that also includes the avoidance of smoking or being overweight and keeping active. The polypill, which combines blood pressure lowering agents, statins, and anti-platelet agents, and its application in preventing heart attacks and strokes was first proposed in a patent application2 in 2000 and in a research paper published in The BMJ in 2003.3 The proposal was based on a comprehensive review of the evidence from observational studies and clinical trials for reducing blood pressure and serum LDL cholesterol and the consequential reduction in the incidence of heart attacks and strokes. The originally proposed polypill composition was a statin, three low dose blood pressure lowering agents, low dose aspirin, and folic acid. It was estimated that this combination, in a single formulation, could prevent about 80% of heart attacks and strokes.3
Subsequently a polypill consisting of a statin and three blood pressure lowering agents was used in a randomised crossover trial published in 20124 which yielded expected reductions in systolic blood pressure (of about 20 mm Hg) and diastolic blood pressure (of about 10 mm Hg) accompanied by around a 40% reduction in LDL cholesterol. The polypill approach as proposed in 2000 is more than a pharmaceutical formulation; it is a public health strategy in which everyone in the population above a specified age (currently judged to be 50 and over) would be offered a polypill without medical examination or testing but simply an inquiry to identify a few specific contraindications. The concept was heralded by the then editor of The BMJ as one of the most important contributions to medicine in 50 years.5
Since its first description, several randomised control trials using various polypill formulations in diverse settings around the world have shown substantial benefits in reducing risk factors and cardiovascular events with minimal side effects. For example, the PolyIran trial6 demonstrated a 33% reduction in major cardiovascular events after five years in the polypill group compared with the usual care group. The preventive effect was increased to 56% among the most adherent, or to 53% after 40 months of follow-up, which allowed realisation of the full effect of several years of statin medication on cardiovascular events. Modelling showed that with 100% uptake and adherence, 2528 person years would be gained per 1000 people receiving the preventive medication, which is substantially more than the estimated 1148 of person years gained with the current NHS health check screening programme offered to 40-74 year olds.7
The NHS health check is a complex risk factor based screening test with the offer of a statin to those assessed as having a 10 year risk of cardiovascular disease greater than 10%. This approach misses many of those who become affected by cardiovascular disease,7 and uptake (around 40%) and adherence are poor. The polypill approach would only require about an 8% uptake to achieve a better clinical outcome. Despite the advantages of simplicity, effectiveness, safety and potential low cost, the polypill approach has, however, not been taken up in practice on any scale so far.
Barriers to implementation and policy considerations
An online polypill prevention programme has been running on a private basis (accessed on polypill.com) for over 10 years in the UK. The service demonstrates the feasibility of the polypill approach which could be adopted widely as part of the NHS. Such a service has not yet been adopted into mainstream practice anywhere in the world even though the World Health Organization has included several polypill formulations on its essential medicines list.8
There are several barriers to implementing the polypill approach,9 though none are insurmountable. Although the polypill, as an unlicensed medicine, cannot be specifically promoted, the service that offers a polypill can. One of the main barriers to uptake is that it involves a shift on the part of the public and healthcare professionals away from a personalised, risk assessment based approach to a public health service in which individuals above a specified age are directly offered preventive medicine in the absence of contraindication.
“Medicalisation” of large sections of the population is cited as a further objection, but the polypill approach is instead a preventive strategy designed to avoid a person becoming a patient. Clear parallels can be drawn with a wide range of other public health programmes—for example, vaccination programmes, salt reduction in food, folic acid fortification of flour, water fluoridation, vitamin supplementation, and HIV and malaria pre-exposure prophylaxis. Concerns have also been raised about potential side effects, such as dizziness or falls from low blood pressure, although these could be overcome by monitoring symptoms. The current online service assesses possible side effects every 20 weeks before issuing a repeat prescription. Furthermore, the individual components of the polypill have been used separately and together for many years with an excellent safety record.
The statutory obligation of local authorities in England to provide an NHS health check is an important barrier. Implementation of the polypill approach would require an acknowledgment that the health checks have not been successful and a policy change is needed. The health check programme and the polypill approach cannot run together: one offers medication only to those above a 10% 10 year risk cut-off based on several risk factors, while the other offers preventive medication to everyone aged 50 and over.
Pathways to implementation
While there is a clear evidence base underpinning the effectiveness of the polypill approach, a key unknown is the uptake and adherence to a large scale, population based programme. A population based demonstration project would be needed to determine this, and it could be evaluated as part of a pilot implementation phase preceding a wider rollout. Although there is not a clear consensus on the design of a wider rollout of the polypill approach, the scale-up of the existing online service in the NHS, with evaluation of outcomes through national health records, is an attractive opportunity for an implementation scheme.
Two policy changes or directives would be required to enable implementation. Firstly, local authorities would need permission to substitute a polypill prevention programme for the NHS health check. Secondly, it would need to be acceptable and even desirable for the polypill prevention programme to use an unlicensed medicine, allowing for reasonable flexibility in formulation without regulatory restraint. For example, replacing atorvastatin with rosuvastatin because of the reduced interaction with other drugs. Another consideration is whether the polypill should be regarded as a consumer item. The designation of the polypill as an over-the-counter formulation that did not require a prescription may be desirable, but an organised implementation programme through primary care would have the advantage of offering an individual invitation to join a polypill prevention programme at age 50 and also enable regular monitoring.
In summary, the evidence base behind the polypill approach is widely accepted as sufficient as a strategy for the primary prevention of heart attacks and strokes. The status quo is not a justifiable option. A large scale, public polypill implementation project is needed to evaluate uptake, adherence, and cost. Overcoming the barriers to implementation will require a bold policy initiative by government to replace NHS health checks with a polypill strategy based on age alone. The new service could be a flagship strategy in Labour’s commitment to disease prevention. We have the means of preventing most heart attacks and strokes, many more than are currently being prevented. All that is required is to translate what we know into action.
Footnotes
This article is based on the discussions and conclusions of participants attending a consensus building seminar sponsored by UCL and held at Goodenough College in London on 3 May 2024. The objective was “To discuss the polypill approach in the primary prevention of heart attacks and strokes (offered to all from age 50), whether it should be implemented in an NHS demonstration project and, if so, how this could be best achieved.” The participants were Jeff Aronson, Kamran Abbasi, Fatima Bangash, Jonathan Bestwick, Mark Caulfield, KK Cheng, John Deanfield, Robin Ferner, Harry Hemingway, Patricia Hewitt, Aroon Hingorani (co-convenor), Rachel Jordan (rapporteur), Rory Maclean, Tom Marshall, John Martin, David Misselbrook, Joan Morris, Sarah Price, Jack Ross, Peter Rothwell, Nilesh Samani, Richard Smith, Barry Subel, Cathie Sudlow, David Taylor, David Wald, Nicholas Wald (co-convenor).
NW is a director of Polypill Ltd which provides an online polypill service on polypill.com for the primary prevention of heart attacks and strokes. The other authors have no interests to declare.