A four-in-one pill that could drastically reduce heart attack deaths has started in trials in Britain last week. Claire O'Connellreports
COULD IT be the ultimate heart pill to ward off all ills? A new "polypill" that combines four commonly prescribed drugs could drastically reduce the death rates from heart attack and stroke and is just starting pilot trials in human volunteers in Britain.
The "Red Heart" pill contains the blood-thinner aspirin, a cholesterol-lowering statin, and an ACE inhibitor and a diuretic to combat high blood pressure.
Researchers believe the once-a-day pill would cost as little as 70 cent per month and could halve the number of deaths from cardiovascular disease and stroke, realising a long-held dream of many doctors, according to a report in the Guardian newspaper.
Putting four well-known and cheap pharmaceutical compounds into a single pill is a simple enough idea, but getting the polypill this far has been a struggle, according to project leader Prof Anthony Rodgers from the University of Auckland.
"The chances of mainstream pharmaceutical industry taking this on are slim," he says. "We spent a few years around about 2000-2002 trying to persuade a number of companies to do this, but got nowhere. Basically, their whole business model is around people paying a few hundred pounds a year for the latest blockbuster drug. A pill with established medicines that halved cardiovascular risk and could be available for £20 a year could be seen as a threat."
However, the project is now underway and the Red Heart pill is currently being manufactured by Indian generics company Dr Reddy's.
This week sees the start of the UK arm of a pilot, which is supported by the British Heart Foundation and the Wellcome Trust and forms part of a larger international trial of the polypill on 700 volunteers. If all goes well, larger clinical trials involving up to 7,000 people are planned for 2009.
Ultimately, a range of cheap polypills could be prescribed to at-risk over-55s in the developed world, according to Prof Simon Thom, clinical professor of cardiovascular pharmacology at Imperial College, London, where the UK pilot is being carried out. He believes that standard versions of the multidrug pill could also be sold affordably over the counter in the developing world, where the rates of cardiovascular disease are soaring thanks to the rapid adoption of Western lifestyles.
Combining more than one drug into a single tablet is not a new approach, but can present challenges for formulation, delivery and testing, particularly if many compounds are involved, says Prof Pat Guiry, who directs the Centre for Synthesis and Chemical Biology at University College Dublin.
"When you have one compound you can work out the physical characteristics of how to keep the tablet to a certain colour, shape, consistency and size," he explains. "Once you have got two compounds they are probably going to have slightly different characteristics.
"It's more of a challenge when you have three and clearly the more you have the tougher it gets."
Now that the Red Heart polypill formulation has been worked out, the challenge is to ensure the single pill is safe and effective, and Guiry notes that the human trials will have to watch for interactions between the drugs.
"They are going to have to do it in a very methodical way, it would have to be carefully done," he says.
However, he sees the benefit of combining commonly prescribed and well characterised medications into a single-dose format, particularly for people who currently take a number of different tablets each day.
"Those people might be asking themselves did I take all four of the drugs or did I take three - if they just have to take one pill, it would be good in a practical sense."
And Trinity College Dublin gerontologist Prof Des O'Neill, who chairs the Irish Heart Foundation's Council on Stroke, cautiously welcomes the prospect of a polypill to tackle cardiovascular disease.
"In essence, it's a helpful idea, particularly if nested within a more broad lifestyle approach that takes smoking, exercise and diet into account. But a little caution is needed, particularly for older people, who are most likely the highest need group, as their individual needs are more complex," says O'Neill.
"While reducing the number of medications is good, on the debit side unpicking a side effect can be challenging - which one was it? - and many older people have mild chronic renal failure where [the diuretic] will have no real effect.
"So, a cautious welcome, and it's important that the trials include enough older people so that we know whether the [drugs] are helpful or not."