Hailed as the new wonder cure, a polypill containing four common drugs to ease the risk of cardiovascular diseases could be what scientists call 'a global mass preventative medication'.
The term, coined by two professors from Queen Mary University, London, in 2003 describes a pill that everyone over 55 would take every day as an anticipatory measure.
The Program to Improve Life and Longevity (PILL) pilot study, a randomised global study published in the medical journal PLoS ONE in May 2011, now suggests the pill, which contains 75mg aspirin, 20mg simvastatin to lower cholesterol, 12.5mg hydrochlorothiazide and 10mg lisinopril, to lower blood pressure, halves the predicted risk, though it also leads to higher rates of side effects than previously thought.
Imperial College London emeritus professor of clinical lipidology Gilbert Thompson spoke to pharmaceutical-technology about whether the polypill will overhaul the cholesterol drugs market, about the dangers of statins, and which new cholesterol drugs promise a successful solution to cardiovascular diseases in the near future.
Elisabeth Fischer: What's behind the widespread interest in a cholesterol polypill?
Gilbert Thompson: The proponents of the idea think that it's going to result in a considerably greater reduction in the prevalence of coronary disease than existing preventive measures.
Personally, I'm not sure if it is such a good idea but the epidemiologists and public health doctors feel the greater the reduction that can be achieved, the better.
EF: Why are you sceptical towards the cholesterol polypill?
GT: The idea is to hand it out to everybody over the age of 55 irrespective of their cardiovascular risk status.
This raises two issues: first of all, you are going to give the pill to an awful lot of people who don't need it, who don't have any risk factors and aren't at increased danger for cardiovascular disease.
There will be a lot of unnecessary medication.
If they hand it out to everybody over the age of 55 it means the entire population of middle-aged and elderly people are patients and not just free living individuals.
By giving it to people who don't need it you are going to put some of them at slightly increased risk of developing side effects, particularly from the point of view of the aspirin component.
Statins are extremely effective drugs and remarkably safe, but occasionally you will come across a person who has a genetic predisposition to develop muscle problems with statins.
If you're just dishing this polypill out without any kind of medical supervision they could come to serious harm. It's a very rare complication, but it's not something which you can totally ignore.
The polypill sounds great in theory but in actual practice I'm not entirely convinced that it's going to work as well as protagonists say it will. Pilot studies have been done but I don't think anybody has yet shown in an actual clinical trial that the intended or expected reductions in risk and event have been achieved, and obviously one will have to wait until these trials are done before one can really make a judgement.
EF: Will people take the polypill even though they feel healthy?
GT: I suppose the person who is being given the polypill won't really know whether or not they are at increased risk of a cardiovascular event. I would have thought, with that being the case, the likelihood of them complying with taking the pill is not all that great.
We know that even in patients who are known to have high cholesterol levels, about 30% have stopped taking their statin tablets altogether within a year. Simply because they lose interest or are non-compliant.
EF: How much do we know about the long-term effects of statins?
GT: There is a slight increase in the likelihood of people taking statins of developing diabetes.
It's slightly less than 10% and the risk is greatest for people who are taking a high dose, but the dose in the polypill would be fairly low. The other issue that concerns me is Alzheimer's disease (AD), which is very much age related. By the age of 80, in western countries, roughly 10% of the population will have developed AD and that increases as the age of the population rises.
If you increase the proportion of the population who survive until the age of 90 by giving them statins then that's going to increase the proportion of the population prone to develop AD.
In the absence of any cure for AD, one wonders whether that is a good thing. This is obviously a bit of a philosophical issue rather than a purely medical one.
I'm not against cardiovascular prevention - in fact I've spent most of my career trying to achieve that. But I've been focussing particularly on people who are at premature risk of dying from coronary disease, especially those with familial hypercholesterolemia, which is a genetically determined condition affecting about one in 500 of the population. It's now clear that if one can detect these people in early life and treat them with statins, they do wonderfully well.
Previously, one would see patients with this condition dying in their teens or before they got to the age of 30.
My approach has been to try to identify people who are high risk, focus on them and treat them properly as patients, rather than just dispense pills to the whole population and hope for the best.
EF: What better alternatives to the polypill are currently out there?
GT: I think the existing way in which prevention is managed is quite sensible. The GP investigates the risk factors in all the people in his practice who he has reason to believe might have an increased risk, particularly those with a family history of heart disease.
Then he or she will measure the blood pressure, the smoking status and the cholesterol in these people, calculate their risk and if it's high, they will treat them.
They will treat the appropriate risk factor with the appropriate drug. They won't just simply hand out the same drugs to everybody in the practice.
The current approach is pretty effective and certainly over the past 20 years the death rate in people below the age of 75 from cardiovascular disease has halved in the UK, which is a considerable reduction.
EF: Is there any space for improvement of cholesterol drugs?
GT: There are other drugs in the pipeline. Statins have completely revolutionised the management of people with high levels of cholesterol. They weren't around when I first started treating patients and so I know exactly what an enormous difference they've made. The way in which statins work is to lower the level of LDL cholesterol, otherwise known as bad cholesterol. Now there are drugs being developed that look at the question of whether raising the level of HDL cholesterol, the so-called good cholesterol, is going to be effective.
So far, the trials have not been very conclusive. One trial was stopped halfway through a few years ago because the patients on the cholesterol HDL raising drug, called torcetrapib, were dying faster than those on the placebo.
But there are other HDL-raising compounds, which are undergoing clinical trials at present. It will be very interesting to see what the outcome of those studies is.
One approach is thyro-mimetic, which is currently undergoing clinical trials. It's a thyroid hormone-like compound but it doesn't have the main thyroid hormone actions of speeding up your metabolism, making you lose weight and stimulating the cardiovascular system. But it does have the effect of lowering the level of LDL in the blood. Those are some of the compounds, which may supplement statins in the future.
EF: What would you say is the most promising approach for the future?
GT: I would have thought that probably it will be a combination of a statin with one of these other compounds. At present, people with severely raised levels of cholesterol are usually treated with a combination of a statin and another drug called exetimibe, a cholesterol absorption blocker.
But I could see that eventually it might be that you have the combination of a statin and one of these other compounds I've mentioned. The ideal situation is to try and get the level of LDL as low as possible and the level of HDL as high as possible. So that combination of LDL-lowering and HDL-raising drugs is a very attractive one.