Tuesday, March 31, 2009

The polypill: Medicine's magic bullet

The capsule costs pennies, contains a simple cocktail of medicines, and halves the number of strokes and heart attacks. Doctors want to hand it out in the first mass medication for the middle-aged in Britain. So why are the big drug companies so uninterested?

The magic bullet, containing five medicines in a single capsule, sharply reduced cholesterol and blood pressure levels and has the potential to "halve cardiovascular events in average middle-aged individuals", the researchers say.

The finding is a major boost for a medication with huge potential against the worldwide epidemic of heart disease and stroke. Doctors say that, if further trials prove successful, all men aged over 50 and women aged over 60 should be offered the pill in what would be the first example of mass medication for the middle-aged in Britain.

Yet no Western pharmaceutical company has shown interest in developing the so-called polypill because it does not promise big profits. It would sell for pennies because its five constituent medicines are cheap, have been around for decades and their patents have expired.

In the UK, one in three men and one in four women die prematurely from heart disease and stroke. In 2005, cardiovascular disease caused more than 208,000 deaths, about four in 10 of all deaths. The idea of combating the heart disease epidemic by combining existing medicines into a drug cocktail called a "polypill" was first proposed six years ago. The pill contains aspirin to prevent blood clots, a statin to lower cholesterol and three blood pressure-lowering agents – a diuretic to remove water from the tissues, a beta-blocker to regulate the heart beat and an ACE inhibitor to relax the arterial muscles.

The current UK strategy of identifying and treating people at high risk of heart disease is failing because one-third of those who have a heart attack have no risk factors and one-third of those die. By giving the pill to everyone, the problem of identifying those at high risk is removed.

When the idea was published in the British Medical Journal in 2003, it was described as a "step of genius" and "possibly the most important paper the journal has published in 50 years". But progress in developing the idea has been slow, and the UK has been left behind.

Now, in the first trial to be published in a mainstream medical journal, researchers from McMaster University, Canada and St John's Medical College, Bangalore, have tested a version of the polypill in 2,000 people in 50 centres in India. The results, published in The Lancet, show that over 12 weeks the polypill reduced blood pressure and cholesterol in a similar way to its individual constituent drugs without increasing side effects. As patients are poor at taking multiple drugs, the single pill combination could "substantially improve adherence and therefore the benefits", they say.

Yesterday, Professor Malcolm Law of the Wolfson Institute of Preventive Medicine in London, one of the originators of the polypill concept, said he was encouraged by the results. "It shows you can make it, it works and it doesn't cause side effects," he said.

He and Professor Nicholas Wald, joint authors of the 2003 BMJ paper, have had talks with the Government's Heart Czar, Roger Boyle, and the Medicines and Healthcare products Regulatory Agency (MHRA) about obtaining a licence. Progress has been held up by a lack of funding and charitable foundations are being approached for support. "We have a patent and work is underway to do the necessary studies to gain a product licence through the MHRA," said Professor Law.

Professor Boyle suggested in 2007 that all middle-aged men and women should take a daily statin, one of the constituents of the polypill. The National Institute for Health and Clinical Excellence (Nice) said last year that more than one million adults at high risk of heart disease were missing out on statins that could save their lives. Nice said GPs failed to identify those at risk because patients were not routinely assessed.

Peter Weissberg, medical director of the British Heart Foundation, said the trial was "good news" because it showed the polypill worked. But it was the first of a series of "very important steps" that had to be taken before it would be clear whether its benefits outweighed its drawbacks. "I am sure there will be a public health benefit in terms of heart attacks saved," he said. "But will there be some people who are inadequately treated? There is scepticism that at the end of the day, one size fits all is going to work. If we are going to medicate the population we have got to show it does reduce heart attacks and strokes. We have got to have a drug that is safe, effective and that people are prepared to take."

The Stroke Association said: "High blood pressure and cholesterol are major causes of stroke and it is important that people take medication to combat these risk factors. By combining these medications in one pill, it will make it easier for people to take their medication. However, it is important that more research and investigation is done into this pill to ensure its safety."
By Jeremy Laurance, Health Editor at The Independent