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
Individuals were selected for the study on the basis of two criteria:
- They needed to be currently taking at least one of the medications in the polypill
- They needed to be aged 50 or over
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.
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
Please read the complete article here.
Sept 8, 2014 - An FDA advisory committee looks at a new cardiovascular polypill about which FDA staff expressed serious reservations http://1.usa.gov/1CNj7AM