The Polypill - is it making a comeback?Simon Curtis - 3 Sep, 2019
Do you remember the polypill? That iconic BMJ cover from back in 2003, claiming it would prevent 80% of heart attacks? Well, the polypill is threatening a comeback, as it has been in the news again this week following the publication of the first big randomised intervention study the PolyIran Study Lancet 2019. This was a cluster randomised controlled trial, in which 6,000 patients in rural Iran aged over 50 were randomised to taking a polypill (containing thiazide, aspirin, statin and ACEi) or having lifestyle advice.
The BBC and other media blazed the headlines that the polypill reduced major cardiovascular events by a third. Your patients may have been interested. However, before we even start on the problems of applicability between people in rural Iran and our patients, the media failed to report the absolute benefits seen. Taking the polypill reduced relative risk by a third, but in absolute terms taking the polypill every day for 5 years reduced the risk of a major CV event for an individual from 9% to 6%. Your patient may now be less interested. Therein lies the problem of applying knowledge that from a public health perspective may have a big impact but for each individual the personal gain may be too small to consider.
One of the fascinating things about doing Hot Topics for so long is seeing how ideas, drugs and medical interventions evolve over time. And in the 16 years since the BMJ made the dramatic claim, detailed in the accompanying paper, that if taken by everyone aged over 55 the polypill could prevent 80% of heart attacks, a lot has changed. Back in 2003 Richard Smith, then editor of the BMJ, wrote an editorial suggesting it was the most important paper the BMJ had published in 50 years. When we presented the ‘polypill papers’ on the Hot Topics course, it was hugely controversial amongst our delegates. Many GPs saw it is a simple, cheap and pragmatic solution to the problem of CVD prevention. Stop smoking, move more, eat healthy and if you want you can also take this pill. Easy. Many more however saw it as medicalisation gone mad, big brother ‘blunderbuss’ medicine that ignored individual biological variation and undermined personal responsibility for healthy lifestyle change. Amongst all the debate however, perhaps the biggest argument for the idea was the ‘prevention paradox’, the fact that many people who have cardiovascular events do not have hypertension or hyperlipidaemia so will be missed if only high risk people are targeted. And perhaps the biggest argument against it was that the claims were based on observational studies and epidemiological data and not on randomised, controlled intervention trials.
Sixteen years later and we are still not prescribing polypills. The zeitgeist has moved on, away from mass medicalisation and towards individualised risk assessment and informed patient choice based on absolute risks and benefits. But perhaps these concepts are the luxuries of developed nations. In low and middle income countries, such as rural Iran, this could provide a pragmatic and affordable way to offer people an intervention to lower their cardiovascular risk above and beyond lifestyle change. Polypills for HIV, TB and malaria have been developed and are widely used in developing countries. So, why not for prevention of cardiovascular disease, which after all remains the world’s biggest killer? Well, the biggest argument against so far has been the lack of evidence from intervention studies and the PolyIran study has now produced evidence of benefit.
So, will we be prescribing Polypills anytime soon? I can’t see it happening here in Europe, there are just too many variables to consider as we strive to practice personalised medicine and furthermore, we still lack intervention data relevant to our patient population. But from a public health perspective in low and middle income countries? That is an interesting idea, and the PolyIran study shows that the polypill may yet have a future.