Philosophically, I have a deep disquiet about the tendency of my profession to medicalise health. While I have no qualms at all about vigorously treating risk factors for heart disease such as high blood pressure and elevated cholesterol, I confess to being a little dubious about the advisability of blindly treating the general population with the cocktail of drugs known as the “polypill”. It has always seemed to me that advocating proper lifestyle changes is a rather better approach than commencing treatment in otherwise normal individuals. Certainly the combined results of exercise, normalising weight, stopping smoking and excessive alcohol and eating healthily seem to match those achieved by consuming a scatter-gun of pharmaceutical agents. It is unsurprising, therefore, that I viewed the following headline with scepticism:
People who take a four-in-one combination pill daily could halve their heart disease and stroke risk, an international trial which received New Zealand funding has suggested.
Previously it had been claimed the “polypill” could reduce heart disease and stroke by 80 percent.
The trial, which included participants from New Zealand, tested a once-a-day polypill, which contained aspirin and agents to lower blood pressure and cholesterol.
Professor Anthony Rodgers of The George Institute for Global Health said the results showed a “halving in heart disease and stroke could be expected for people taking this polypill long-term”.
Let me say at the outset that I have no issue with the study itself. It seems to me to have been well-run and its conclusions are reasonable. You can access the actual study here. In addition, the actual premise of the polypill is perfectly reasonable, my philosophical objections notwithstanding. The values we set for “normal” blood pressure and “normal” cholesterol are essentially arbitrary – the lower your blood pressure and cholesterol, the lower your chances are of suffering a heart attack or stroke. It is therefore quite plausible that a pill that lowers a healthy person’s “normal” blood pressure and cholesterol would lower the risk of heart disease. This study does indeed demonstrate quite nicely that treating people in the “normal” range does lower their risk factors for heart disease.
The study also concentrates, not on all healthy people, but on the subset of people whose risk for heart disease is more than a 7.5% in the next five years (mainly, older males, smokers and diabetics) and whose blood pressure and cholesterol are not high enough to treat formally. This is significant, because it does, at least partially, overcome my philosophical problems with the polypill. At least these persons are demonstrably at risk – which is why we treat blood pressure and cholesterol in the first place. Unfortunately, it also begs the question as to why we do not treat such people formally with single formula, targeted products. If we are keen to lower their risk factors with a polypill, surely it would be more worthwhile to do this in a more controlled fashion. Perhaps those arbitrary limits that we cherish should be lowered for this subset of patients? They are certainly lowered for diabetics already – we lower blood pressure and cholesterol quite aggressively in these people.
These are not merely academic musings. This particular study demonstrated that the side effect profile of the polypill was substantially worse than originally proclaimed when the polypill was first mooted. This is a fairly alarming finding, as most of the people in the study would be considered healthy by the general population and most doctors. But the problem is deeper than this, because the study only followed up the subjects for 12 weeks. Thus no long term side effects were studied, including the well-known side effects of the individual components – gastric bleeding from aspirin, muscle wasting and pains from simvastatin, cramps and gout from hydrochlorthiazide and a chronic cough and severe swelling from lisinopril. Multiple products in the same pill also make it a lot harder to determine what drug is causing what effect. This is why there are few combination products on the market – and almost all of them contain only two drugs.
In addition, the study showed that the actual lowering of risk was by 50%, instead of the postulated 80%. This may well mean that, for many people, the drug combination has too little benefit for the potential risk. Although 50% might sound a lot, bear in mind that the absolute benefit depends on the absolute risk – a person at 5% overall risk knocks only 2.5% off the absolute risk. someone at 20% knocks off 10% – a much greater gain.
And that finally brings me to the topic of risk and why I have such skepticism about the original newspaper article. The headline indicates that heart disease risk is halved. This is not what the study says at all. The study demonstrates that the estimated risk of heart disease is halved. Least you think I am simply being picky here, I must point out that the Framingham study, that these risks are calculated upon, merely worked out the risk at a certain level of risk factors. Sadly, it does not always follow that lowering those risk factors, reduces the risk. While reducing blood pressure certainly reduces your risk of strokes, it makes much less impact on your risk of heart attacks – the effect being much less linear and quite drug-dependent. Aspirin has been shown recently to make no appreciable difference to the incidence of your first heart attack (but does lower your risk of another). Thiazide diuretics, such as hydrochlorthiazide, do not appear to lower your risk of heart attacks at all.
There is therefore some reason to be skeptical that the risk-factor-lowering effects of the polypill lowers actual risk. Until a LARGE polypill trial runs for 10 years, and uses actual heart attack and death from heart attacks as their endpoints, we will not really know whether these drugs have any place everyday use. I, for one, will not be advocating their use based on this, or any of the current crop of trials.