It’s easy to fall for the polypill hype, but the reality is this medication has never been proven to benefit anyone

There’s been a ton of press over the last couple of days regarding a study of what is termed the ‘polypill’ – a combination medication conceived more than a decade ago with, supposedly, the prevention of heart disease and stroke in mind. The original ‘formulation’ combined blood pressure- and cholesterol-lowering medications, along with aspirin and vitamin B12. From time to time in the scientific literature we have seen studies which purport to support the idea of polypill taking for disease prevention. And the latest of these was published this week. Here, in short, is the study design and what it showed. After that, I’ll offer my own interpretation of the data.

This latest study tested the impact of a polypill comprising the following drugs:

  • amlodipine (blood pressure lowering medication) – 2.5 mg
  • losartan (blood pressure lowering medication) – 25 mg
  • hydrochlorothiazide (blood pressure lowering medication) – 12.5 mg
  • simvastatin (a statin) – 40 mg

The medication was given for 12 weeks to men and women aged 50 and over. At another time, they took a placebo for 12 weeks. In this sense, individuals acted as their own ‘controls’ in this study. Individuals were selected for the study on the basis of two criteria:

  1. They needed to be currently taking at least one of the medications in the polypill
  2. They needed to be aged 50 or over

The impact on blood pressure and cholesterol levels was assessed. The polypill did bring significant reductions here. The authors estimate from the degree of reductions here that heart disease and stroke would be reduced by 72 and 64 per cent respectively. Impressive numbers. There’s talk of this extending life by a decade or more.

But here’s the thing: this study simply can’t be used to judge whether the polypill prevent cardiovascular disease and delays death. These ideas are based on speculation based on the idea that lowering blood pressure and cholesterol translates into significant benefits for health. Yet, as I explored most recently here and here, blood pressure and statin medications are generally very ineffective for the purposes of disease prevention and preventing death. Most people who take these drugs just won’t benefit.

This is particularly the case when individuals are deemed to be at low risk of cardiovascular disease. Normally, medication is prescribed on the basis of, say, blood pressure or cholesterol levels. But not in this study: here people were selected on the basis of age, irrespective of perceived risk. Of course it’s possible that some might benefit from the polypill, but it’s also likely that many more will not.

And of course the drugs in the polypill are not without risk. Any one of these medications on its own might cause problems, but the risk is magnified when medication are taken in combination. The design of the study (individuals had to be on at least one of the drugs in the polypill prior to the study) essentially preselects for individuals who, compared to members of the general population, are more likely to tolerate the medication being tested. So, risk of side-effects in the study population would be generally lower than we would expect to see in real life.

But, all of this is a diversion from the main point that we simply cannot predict the value of a drug on its impact on so-called ‘surrogate markers’ such as blood pressure and cholesterol. I mean, who would have predicted that ezetimibe, a potent cholesterol-lowerer, would never be shown to have benefits for health, or that the drug torcetrapib (which lowers ‘bad’ cholesterol and raises ‘good’ cholesterol) happens to increase the risk of people dying?

If we want to know how effective the polypill is, we need to test its impact on health. What impact does the polypill have on risk of heart disease, stroke and overall risk of death? We just don’t know because this latest study does not tell us. There are four previous polypill studies in the literature, and none of them look at these critically important ‘end points’ or ‘outcomes’ either.

The lead author of the latest study is David Wald, son of Professor Sir Nicholas Wald, co-inventor of the polypill. Professor Wald and a colleague (Professor Malcom Law) hold a polypill patent. I suspect they have at least some desire to cash in on their invention. But if they want to do that, why not test the polypill in a way which does not lead to wild speculation but cool hard facts? Perhaps if the polypill was properly studied we’d get to see that, like so many drugs, the ‘expected’ benefits fail to materialise. Maybe it’s better to keep the dream alive with a string of studies and articles that allow rampant speculation and uber-enthusiasm but simply fail to tell us what we really need to know.

References:

1. Wald DS, et al (2012) Randomized Polypill Crossover Trial in People Aged 50 and Over. PLoS ONE 7(7): e41297. doi:10.1371/journal.pone.0041297

15 Responses to It’s easy to fall for the polypill hype, but the reality is this medication has never been proven to benefit anyone

  1. Feona 20 July 2012 at 6:04 pm #

    And, of course, even more money to be made by prescribing yet more pills to counteract the inevitable side effects of the polypill!

  2. hilda glickman 20 July 2012 at 6:51 pm #

    Why don’t doctors at least try to lower blood pressure etc with nutrients first? I giess it’s because they don’t know much about the impact of food and nutrients on health. If you think nutrients are not powerful think of yourself as a baby and then now. How did you get like that? From food. Poweful stuff!

  3. Robin Davies 20 July 2012 at 9:56 pm #

    Why on earth should I take 3 different bp lowering drugs at the same time when beetroot jiuce does the same job perfectly?

  4. John Walker 20 July 2012 at 11:23 pm #

    Does beetroot juice have this effect? Any science I can read to substatiate this? I eat lots of beetroot, (Pickled though, because as beetroot comes, it’s like eating a spadeful of earth! )

  5. Chris 21 July 2012 at 2:15 pm #

    Confusing… Nitrates seem to be the given reason for Beetroot lowering blood pressure but nitrates are frowned upon elsewhere in the paleoshere. I also thought there were nitrates in meat so if that is correct meat would have the same effect, No?

  6. Eddie Mitchell 21 July 2012 at 2:48 pm #

    “Two of the ingredients of the polypill: Amlodipine (blood pressure lowering medication) – 2.5 mg. Simvastatin (a statin) – 40 mg.

    FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. Do not exceed 20 mg simvastatin daily with Amlodipine.”

    http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm

    This medication is going the way of Actos and Avandia before it gets off the ground. Yet another med with little if any benefit for most, but built in side effects leading to serious injury and death. Looks like a nice earner for the statinaters.

  7. Dr John Briffa 21 July 2012 at 3:05 pm #

    Eddie

    That’s very interesting about the interaction with amlodipine (I wasn’t aware of it).

    More than a decade after the polypill was conceived, it remains to be subjected to testing with regard to clinical endpoints. Makes me wonder, to be honest, whether it’s inventors and patent-holders are really committed to proving the benefits (or otherwise) of this ‘drug’.

  8. Magarietha 21 July 2012 at 7:05 pm #

    I heard yesterday morn, one Dr. David Lloyd (an olympics volunteer) say on Sky News that everyone should take it. That your bp and cholesterol can never be too low. A super fit sports news anchor challenged him about taking pills and he told HER that right now her bp and cholesterol is too high and she answered NO! both low and low. And he said yet again: Doesn’t matter must still come down more… that there’s huge evidence that if you take this stuff you will live longer. He was adamant. he probably would get and apoplexy re. the low carb diet, which halved my cholesterol – all of it.

  9. Eddie Mitchell 21 July 2012 at 10:51 pm #

    Ah, lowcarb, the highly dangerous and not approved by DUK and the NHS diet. The diet that can reduce a type two diabetics BG numbers to non diabetic in a week, without medication.. Can reduce BP without drugs. Can improve HDL cholesterol and reduce Trigs from 5 to 1 in a few months. The big problem, there is no money for big pharma or the junk food multi-national food companies. No brown envelopes to corrupt lobbying members of parliament etc. etc.

    This is not rocket science, base your food on green non starchy vegetables, and lowcarb fruits. Add some high quality protein and fats man has ate since the beginning of time. Get a good nights sleep and some easy exercise such as swimming and walking. You know it makes sense, why fight it.

  10. Doc´s Opinon 23 July 2012 at 1:45 am #

    I totally agree with you Dr. Briffa. Reductions in blood pressure and cholesterol levels cannot be translated into a reduction in stroke and heart disease or improved survival. Moreover, as pointed out by Eddie Mitchell there have been a number of reports recently on the interaction between simvastatin and other commonly used drugs, among them amlodiopine and other commonly used calcium channel blockers.

    It has been suggested that the polypill may become useful in “poorer” countries because it is cheap. Thus, a large number of people may be treated with relatively little costs, per capita. Many of the polypill studies so far have been performed in India. However, most experts believe that therapy in “richer” countries will continue to be tailored. We live in a strange world don´t we.

  11. blackdog 23 July 2012 at 2:37 pm #

    Chris, the chemical in beetroot and most root vegetables is nitrite, not nitrate. This can ‘morph’ into nitrosamines in the presence of high heat and/or stomach acid. It’s the preservative added to cooked meat, bacons and sausage to stave off botulism. Nitrosamines are carcinogenic but not in the presence of vitamin C which has to added to these products to prevent stomach cancer. It is alleged that high intake of preserved meats can increase the possibility of cancers, but this is only correlation. Normal grass fed meats have quite low levels and vegetables quite high levels especially when fertalised with… nitrates.
    High intakes of beets is unlikely to have much effect on BP except if the extracted macronutrients present are utilised, some of which may increase nitric oxide production which dilates blood vessels and thus lowers BP. But nitric oxide half life is only a few seconds so you would have to have a continuous supply, which the body does generate, but which can wane with age and disease.
    I would always keep root vegetable intake within bounds, take some Vitamin C every day, aim for organics which do not use nitrate fertalisers and remember that most will also have a high carbohydrate content which will push up plasma glucose and over time the resultantant side effect of a higher BP

  12. Chris 23 July 2012 at 6:47 pm #

    #blackdog (love the name btw – one of my fav led zep songs), thanks for that useful response and straightening out my confusion. Grow my own organic veg including a few beetroot, many brassica’s, onions, garlic shallots and leaks – and to the bewilderment of the whole allotment site – no potatoes. The old boys really scratch their heads on that one… :-)

  13. Karl 24 July 2012 at 2:29 pm #

    A possible limitation in large-scale prevention of stroke and cardiac mortality with this type of treatment is that mortality from these disease classes is being increasingly pushed up in the oldest age groups, and there may be insufficient evidence for the benefits of aggressively reducing cholesterol and blood pressure among old people with slightly elevated readings.

    The controversies surrounding statins or other lipid-lowering agents for primary prevention have been mentioned earlier in this blog. As for blood pressure lowering, in a meta-analysis of epidemiological studies on people without previous vascular disease (Lewington et. al., Lancet 2002, pmid 12493255), 20/10 mm lower systolic bp/diastolic bp meant about 60 percent lower hazards for mortality from stroke, ischemic heart disease and other vascular disease in 40–49 year olds, but only about 30 percent lower hazards in 80–89 year olds. Moreover, lowering bp with drugs may not have effects equivalent to these observed correlations, and there is some evidence from clinical trials that lowering bp beyond about 130/80 may even increase the hazards of cardiac events and circulatory mortality, especially in old people, and people with preexisting cardiac disease, perhaps due to the risk of insufficient perfusion (Chrysant, World J Cardiol. 2011, pmid 21499494).

  14. Robin Davies 24 July 2012 at 7:02 pm #

    Here’s some info on the Beetroot juice story:

    http://www.nhs.uk/news/2010/06June/Pages/Beetroot-juice-and-blood-pressure.aspx

  15. Doc´s Opinion 26 July 2012 at 6:49 pm #

    The effect of the polypill on surroagte end points such as blood pressure and cholesterol and cholesterol is not surprising considering the dugs that are used; blood presure lowering drugs and a cholesterol lowering drug. The essential question however is whether this will translate into improved survival and fewer clinical events in a huge heterogenous population. In a recently published polypill study, side effects were more common than expected. http://www.ncbi.nlm.nih.gov/pubmed/21647425

    The clinical efficacy of the polypill has to be tested in a large-scale clinical trial before it is launched. However, it is still uncertain which combination of drugs would be best, should aspirin be included and so on. So far, the developing countries have been the main target for such a clinical trial. Howvever, the feasibility of conducting such a large-scale Polypill clinical trial in developing countries remains unclear.

Leave a Reply