Health: Polypill

Lord Turnberg Excerpts

Monday 7th July 2014 Lords Chamber

[Lord Turnberg (Lab)]

My Lords, I too am grateful to my noble friend Lord Hunt for introducing this debate. It is pretty obvious that he, like me, has been briefed by Sir Nick Wald—and I suspect that the noble Earl may have heard a little from him too—so if what I say sounds a little familiar, I hope he will forgive me. Heart attacks and strokes remain among the biggest killers, despite the improvements in mortality rates in recent years. We know many of the risk factors—smoking, alcohol, obesity, salt and lack of exercise—and we must not be distracted, as the noble Baroness, Lady Brinton, says, from dealing with these public health issues. They are not mutually exclusive, of course.

We know that we should do more to detect and treat high blood pressure and raised blood cholesterol levels, but there is one important risk factor that we can do little about. That is age. There is a straight-line relationship between age and the incidence of heart attacks and stroke. The older you are, the higher the risk. The most striking thing about this is that about half of those getting one of these killers do not have one or other of the conventional risk factors—they have normal cholesterol and normal blood pressure. They come as a surprise in people thought to be fit, and it is in these unsuspected and unsuspecting individuals where the polypill may play a role.

The rationale for the polypill relies on a number of basic principles and here I rely specifically on Sir Nick Wald’s briefing, so what I say, as I pointed out, may not be entirely novel. First, we know that using drugs to lower a raised serum LDL cholesterol reduces the rate of heart attacks, and lowering the raised blood pressure reduces the incidence of strokes, but the intriguing observation is that the same drugs reduce even normal levels of cholesterol or blood pressure to a similar proportion as in those with raised values.

Furthermore—and here is the nub of the argument—lowering even normal levels reduces the risk of heart attacks and stroke. For example, Nick Wald calculates that a fall in blood pressure of 10 millimetres of mercury reduces the risk of stroke by about 60% and reducing serum LDL by 1 millimole per litre lowers the risk of coronary artery disease by 40%. The fact is that there does not appear to be a lower limit below which reducing blood pressure or cholesterol is not effective in reducing risk.

The second principle is that you can achieve as good or better effect in reducing blood pressure from a combination of two or more hypotensive drugs given in half or lower doses than a single drug given in a normal dose, and in this way markedly reduce the incidence of side effects. You get the same impact on blood pressure with many fewer side effects from a combination of half doses.

Therefore, combining these pieces of evidence—risk increasing with age, lowering risk factors even when they are seemingly in the normal range, and combining low doses of drugs to reduce side effects—leads to a conclusion that points to a need to give polypills as a preventive measure to those at risk, namely all the population over the age of 55, say, regardless of their conventional risk profile. Indeed, if they have other more obvious risk factors they are likely to be treated for them by one means or another already. It is the unsuspecting population where a polypill is most likely to be effective. In these, it lowers cholesterol and blood pressure as well as risk.

Nick Wald has suggested that one in three individuals taking a polypill containing small doses of simvastatin, losartan, amlodipine and hydrochlorothiazide would live an extra eight years than they would have done without the pill. It could reasonably be concluded that we should be giving everyone over 55 a polypill of this type, and it would help those harbouring unsuspected coronary artery disease or strokes. If this were a preventive programme like vaccination, as my noble friend suggested, we probably would not hesitate, but of course it is not a one-off, single shot like a vaccine. It is to be taken life long, every day, as a prophylactic treatment, more like the contraceptive pill to prevent pregnancy, although of course for rather longer.

So many issues would have to be overcome, and a number of critics of the mass medication that such a programme would entail have to be answered. There is the question of regulation. Although all the constituents of the pill have been through all the regulators and are in fact well out of patent, the MHRA and MEA may well need convincing that the combinations do not need further appraisal and approval. There is the question of side-effects. Although doses are low, there are undoubted side-effects with all the constituents of the pill, even in the low doses used here. They may well become significant when trying to reach whole populations.

Some say that we are already an overmedicalised society and we do not need yet more pills for everyone. I am not sure that that is a terribly good argument, because we rely quite heavily for our longevity on many of the medicines we take. I am one of the few, it seems, who is on simvastatin without side-effects, out of a huge population who are similar to me. In any case, no one is forced to take drugs if they do not want to. Nevertheless, those are views that we cannot easily dismiss and are to be taken seriously.

We come to the question of whether the polypill should be available for prescription on the NHS or simply over the counter at pharmacists. It is probably very cheap, and the economic value of preventing those diseases is a strong argument for prescription. It would at least allow us to get a clear angle on the number and incidence of side-effects, which free availability would not. It would allow doctors the opportunity to assess their patients for other preventable risk factors at the same time, which we have to do something about. On the other hand, an approach in which people simply decide whether to buy the pill over the counter is certainly more libertarian, but would probably not make a great impact on the epidemiology of those diseases, nor on the health of the nation.

There are certainly interesting debates to be had, and I am very grateful to the noble Lord, Lord Hunt, for starting us off on this topic.

[Lord Willis of Knaresborough (LD)]

I am grateful to the noble Lord for giving way. One issue raised earlier was about the dosage and combining those dosages in relation to particular side-effects. It was only 12 months ago, I think, that NICE advised against giving particular doses of simvastatin together with a modifier. When doses are given separately, you can take the evidence and change them. When they are combined in a polypill, that goes out of the window and you are left with all the elements at the dosages that have been agreed. Is that not an argument for retaining the current position of giving separate dosages rather than combining them all?

[Lord Turnberg]

Those are very good points. The doses used in polypills are very low, in fact—20 milligrams of simvastatin, when the normal dose is 40 to 80 milligrams. The other drugs in the polypill are half doses. The point is that, if you have raised LDL cholesterol or raised blood pressure, you should certainly be on the treatments; they have been shown to be effective. It is people who do not have raised cholesterol or raised blood pressure who we are aiming to treat—or to prevent their diseases—so it is a different situation. The point about safety is important. It is clear that we need and should have proper clinical trials of those doses, but the impact of such doses, from what we know about them in this combination, is that they are likely to be safe in the vast majority of cases. What we do not know is the number who will get side-effects.

[Lord Hunt of Kings Heath (Lab)]

My noble friend, and other noble Lords, mentioned the importance of clinical trials, which I am sure is absolutely right. Is not the problem here that in fact no pharmaceutical company will conduct a clinical trial because all the drugs used in combination in the polypill are off-patent, so there can be no protection of that research by any company taking it forward? So there is, if you like, a block here, although people can see the potential benefits. Rightly, noble Lords are asking for clinical research, but there is no possibility of that happening unless the Government take a hand themselves, which is why the debate on antibiotics is interesting. They are completely separate subjects, but the Government had to step in there because, at the moment, the market simply cannot respond to the issue.

[Lord Turnberg]

I agree entirely. I think that it will be difficult for the drug firms themselves to conduct trials because these are generics and they are manufactured by a number of companies. The only way forward, I suspect, if we are to have a clinical trial, is through NHS funding—that sort of trial. My final remark is that I very much look forward to the noble Earl’s response.

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[The Parliamentary Under-Secretary of State, Department of Health (Earl Howe) (Con)]

My Lords, I thank the noble Lord, Lord Hunt, for giving us the opportunity to debate a particularly interesting subject and for having elicited a number of very well informed speeches. In calling for this debate, he has done the House a considerable service by enabling noble Lords, including myself, to bring ourselves up to date on what progress has been made in the development of the polypill concept. As has been said, heart attacks and strokes are major health issues in the western world and a growing issue in the developing world. Reducing mortality for people with cardiovascular disease and improving their outcomes is a key priority for the Government. We have made it clear, through the NHS and public health outcome frameworks and the Government’s mandate to NHS England, that we want to see action taken across the health system to reduce avoidable premature mortality from cardiovascular disease.

The 2013 call to action on premature mortality set out the Government’s ambition for England to be among the best in Europe in tackling the leading causes of early death, including cardiovascular disease. In April this year, we published Living Well for Longer, which brings together what the health and care system will do to meet this challenge.

There has been a great deal of interest in the polypill and its potential for reducing the risk of heart disease over the years. It may surprise some noble Lords that the concept was first introduced into the scientific and public domain as far back as 2003. It was proposed in an article in the British Medical Journal by two people whose names have been mentioned already, Professors Nicholas Wald and Malcolm Law of the Wolfson Institute of Preventive Medicine. Using mathematical modelling, they estimated that a polypill comprising a statin, aspirin, a combination of three blood pressure lowering drugs and folic acid, could reduce heart disease events by 88% and stroke by 80%. Their article concluded that their proposed polypill could,

“largely prevent heart attacks and stroke if taken by everyone aged 55 and older and everyone with existing cardiovascular disease.”

Although the effectiveness of the combined drug and any possible side-effects had yet to be evidenced though patient trials, this captured the imagination of the public health research community, particularly for the prevention of non-communicable diseases such as cardiovascular disease.

Essentially, the polypill is a combination of multiple medicines which aims to prevent or reduce the risk of cardiovascular disease: that is, strokes and heart attacks. Each of the constituent medicines is either at the current recommended dose or at lower doses. The premise is that these combinations should be used in preference to using the same medicines separately. In practice, the polypill can refer to either the fixed-dose combination medicine to reduce cardiovascular risk, patented as the polypill, or any other fixed-dose combination medicine, such as the red heart pill. However, any discussion of polypills is complicated by the huge range of drugs which might be included in any combination.

Polypill active ingredients are licensed separately as medicines and well established in their own right; their use together in fixed combination is what is novel. Just like any other medicine, any application for a marketing authorisation for a polypill needs to be supported by data demonstrating that its quality, safety and efficacy are satisfactory and that the risk-to-benefit profile is favourable for the proposed treatment before such an authorisation or licence can be granted.

My noble friend Lady Brinton drew attention to the side-effects of polypills and statins. She was absolutely right to do so. My information is that the evidence is not yet there on the side-effects of the polypill. Patient safety must of course be paramount in that context.

No polypills are currently licensed for use in the UK for the prevention of heart attack or stroke. I understand that the Medicines and Healthcare products Regulatory Agency has provided scientific advice to a number of sponsors and companies for combination products of this type. However, no application has yet been made to the licensing authorities. In the event that a marketing authorisation proposal is submitted, the data supporting any claims for benefit in the stated patient population, together with any evidence of adverse events, will be carefully reviewed. Only if the overall balance of benefits versus risks is favourable will a marketing authorisation be granted.

Without a marketing authorisation, as the noble Lord will know, doctors can prescribe an unlicensed medicine under their own professional responsibility. That addresses one question raised by the noble Lord, Lord Turnberg, as to whether it is in theory available on the NHS. The answer would be yes, in those circumstances, but any national action to promote the use of a drug that is not licensed is out of the question, as I am sure he is aware. I understand that there are several clinical trials of polypill products in progress in various countries and it will be interesting to see the results.

The noble Lord, Lord Hunt, questioned whether it was the fear of additional workload that was deterring doctors in the context of the polypill. My information is that the evidence on that front is as yet unavailable one way or the other, as regards the primary prevention setting, but that clinical studies are now under way. Indeed, I have in front of me the details of three polypill phase 3 clinical trials which had either completed or were close to completion as of May 2014. I can let the noble Lord have details of those trials if he would like me to do so.

The noble Lord, Lord Turnberg, raised the possibility that the polypill could be prescribed to those people who do not fall into the risk group. That is, of course, the primary prevention group. I am advised, though, that as age advances, the risk of side-effects also increases proportionally. I suggest that before embarking on a course of this nature, we would need evidence that the polypill influences benefit more than risk. We therefore come back to the issue of clinical trials in order to demonstrate that.

Having said that, to answer another of the noble Lord’s questions, I accept that the polypill could be more convenient for some patients and could help them to adhere to their medicines. Whether it would prove cost-effective is something that NICE might in due course consider.

I know that not everyone is convinced by the polypill. There are, for instance, concerns about the medicalisation of otherwise healthy people. Even by its proponents it is seen as secondary to other forms of prevention. Professor Wald himself is quoted as saying:

“This is not the solution for primary prevention … Primary prevention requires education of the public. As a priority this is much more important than any polypill”.

There is a range of population-based interventions that could be put in place to reduce the risk of cardiovascular disease. Each has its pros and cons and may be suitable for some patients and in different circumstances. We know that many premature deaths and illnesses could be avoided by improving lifestyles. The Government’s public health programme includes national ambitions to reduce smoking, obesity, physical inactivity and the harmful use of alcohol—all with appropriate metrics included in the public health outcomes framework.

In addition, through the NHS Health Check programme people between the ages of 40 and 74 are offered a range of tests that include measuring their cholesterol and blood pressure levels. The check has been designed primarily to help healthcare professionals identify cardiovascular risk in the adult population earlier so that steps can be taken to reduce it, but it is worth emphasising that it is also targeted at a range of other conditions.

All 152 local authorities are now offering the NHS Health Check programme, which is a significant milestone in the programme’s evolution. In 2013-14 a total of 2.8 million people—almost 20% of the eligible population—were offered an NHS health check, and just over 1.4 million of them received one, giving a take-up rate of 50%. This is the greatest number of NHS health checks offered and accepted in one year since the programme began.

[Lord Turnberg]

That is all extremely credible. However, the polypill is aimed at those who have passed the health check with flying colours—that is, they have normal cholesterol and blood pressure, do not smoke and are not overweight. It is with this group of individuals, who are not suspected of having the liability to develop a heart attack or stroke, where it seems to have its place.

[Earl Howe]

Again, that is the primary prevention group, and the point that I was seeking to convey earlier was that we would need evidence that the benefit-to-risk ratio was sufficiently positive before proceeding down that course. That is not to say that it is not, but there is work to be done to prove it.

In March 2013 the Cardiovascular Disease Outcomes Strategy was published. This set out possible actions within the current legislative framework, systems architecture and financial settlement to deliver improved outcomes for people with CVD. It set out a framework for 10 actions that would make a real difference in improving outcomes for patients and their families. While I could expatiate on that subject, I am told that my time is drawing to a close, so suffice it to say that I hope that noble Lords have found today’s debate as interesting as I have.

The polypill is certainly an interesting concept. It may be that this type of approach would be more suitable in developing countries, where the real epidemics of cardiovascular disease are building up and where clinical trials are taking place, rather than in a more sophisticated healthcare system such as ours, where prevention and tailored therapy are more the norm. Time will tell.

On the issue of market failure, which was introduced by the noble Lord, Lord Hunt, I am not convinced that the same arguments apply to the polypill as apply to antimicrobials. For one thing, there are a number of clinical trials of polypills in progress, as I mentioned, and the MHRA has provided scientific advice to a number of companies, so clearly there is commercial interest out there. We do, however, welcome any technologies that contribute to providing the best treatment for people with cardiovascular disease.

In answer to the main question of the noble Lord, Lord Hunt, of whether the Government will consider playing a more active role in this debate, I would certainly be interested in looking at the noble Lord’s proposals in more detail and would be happy to discuss the matter with him at a suitable moment. With that, I thank him once again for introducing this extremely interesting topic for our consideration.