The Polypill: conventional medicine or quackery?

Simvastatin, hydrochlorothiazide, losartan, and amlodipine. If asked to classify those things as either "conventional medicine" or "quackery", most people would doubtless choose the former.

However, everything depends on context.

A combination of those 4 drugs is currently being marketed as a "Polypill". The idea is that the combination of drugs helps to reduce blood pressure and cholesterol, which in turn reduces the risk of heart attack or stroke. Now, the idea of using drugs to reduce blood pressure or cholesterol and hence reduce cardiovascular risk is nothing new, and is undoubtedly a well established part of conventional medicine, with an impressive evidence base to back it up.

But in general, such medication is currently only used for those people judged to be at increased cardiovascular risk, perhaps as a result of high blood pressure. What is new is the idea of giving all these drugs together as a combination Polypill to everyone over the age of 50, irrespective of their cardiovascular risk profile.

Well, I say "new". In fact, the idea has been around since 2003, when it was proposed in an article in the British Medical Journal. It's actually not a completely crazy idea. We know that the components of the Polypill can reduce cardiovascular risk in some patients. Maybe putting them all together can reduce cardiovascular risk even more. Maybe they reduce it so much that they reduce it even for people who are not at particularly high risk in the first place.

But you'll notice there are a lot of "maybe"s there. The Polypill article claimed that the Polypill could reduce cardiovascular risk by over 80%, but this was based on a whole series of heroic assumptions. The main assumptions were that the risk reductions of the various components of the pill would be additive, and that the risk reductions would apply to those initially at low risk as much as to those at high risk. As I wrote in a rapid response at the time, those assumptions are untested.

10 years later, the assumptions remain largely untested. The Polypill website reports a clinical trial which looked at short-term effects on blood pressure and cholesterol, so we do at least now know that the Polypill can reduce blood pressure and cholesterol over a period of 12 weeks in highly selected patients, but I don't think that was ever in doubt. What is noticeably lacking is any data on cardiovascular outcomes. We simply do not know the extent to which the Polypill reduces cardiovascular risk.

Despite this complete lack of evidence that the benefits of the Polypill are as claimed, they are now being marketed via a website which makes a bold claim that it can reduce the risk of heart attack and stroke by two thirds. At least that's been toned down somewhat since the more outrageous original claim of a more than 80% reduction, but it is still an utterly evidence-free claim.

And this, dear reader, is why I believe we are looking at quackery here. Although the components of the Polypill are indeed conventional drugs with a good evidence base in appropriate patients, they are being sold on the basis of dramatic but unsubstantiated claims. That is the stuff of quackery.

It is interesting to read a quote from Prof Nicholas Wald, one of those marketing the Polypill:

"You need randomised trials that demonstrate efficacy and safety for each component and in combination. It’s so difficult that for practical purposes it’s impossible”

Doesn't that claim about it being "too difficult" to do randomised trials sound familiar? Homeopaths also like to claim that the reason they don't have randomised trials supporting their products is that they are "too difficult". To be fair, it certainly is difficult to do a randomised clinical trial looking at cardiovascular outcomes: you typically need to recruit many thousands of patients and follow them up for several years. However, it's not impossible, and many such trials have been done.

But given that the trial has not been done, there is no excuse for making claims about the Polypill as if it had. To do so is nothing other than quackery.

And not only do we not know the extent to which the Polypill reduces cardiovascular risk, the fact that it has not been tested in long term clinical trials means that we also lack information about its safety. Although the drugs used in the Polypill are well established drugs with reasonably good safety records, they are not completely devoid of side effects, and we do not really know whether the combination of drugs introduces new safety issues. Crucially, we really have no information to judge whether the benefits outweigh the risks.

This lack of information on the risk-benefit ratio is of particular concern for people who are not at high cardiovascular risk: exactly the people at whom the Polypill is being marketed (those at high cardiovascular risk may well already be receiving treatment within the normal system of conventional medicine). For those at low risk of a heart attack in the first place, then even if the Polypill results in a substantial reduction in their relative risk, the reduction in their absolute risk will be tiny. The risk of side effects, unless it's truly negligible, may well then outweigh any benefits.

But this does not stop the marketers telling people that the Polypill will benefit them and selling it to them anyway. This is quackery.

We should also note that the combination pill is not, as far as I have been able to discover, licensed in the UK. I would have thought this makes the Polypill website illegal, although I find it hard to believe that they would not have taken legal advice before launching the website, so perhaps I'm wrong about that. But in any case, it's a worry. When a medicine is unlicensed, apart from the concerns about efficacy and safety that I've already discussed, we do not have the same guarantees of pharmaceutical quality that we do from a licensed product. How can we be sure that the ingredients are of described, are of good quality, and do not contain unsafe impurities?

Now, don't get me wrong. I'm not saying that the Polypill is a bad idea. It's an interesting idea, which is certainly worthy of study. What I am saying is that to market the Polypill to the general public with impressive sounding but unsubstantiated claims before it has been properly studied is pure quackery.