By Krishna Chinttapalli London

A combination pill containing six different drugs could reduce mortality from strokes and myocardial infarctions by 88%, according to a recent study in the BMJ (2003;326:1419-22). Dubbed the "polypill," it would be intended as a preventive measure and be taken once daily by everyone over 55 years of age and younger people with a clinical history of cardiovascular disease.

The researchers, Nicholas Wald and Malcolm Law, from Queen Mary's School of Medicine and Dentistry, London, performed a series of meta-analyses of existing data on the effects of different types of drugs used for the management of strokes and cardiovascular disease. From this they have calculated that the optimal formulation of a single pill comprises low dose aspirin, one statin, folic acid, and three blood pressure lowering drugs of different classes at half the standard dose. These drugs would target four different risk factors, namely platelet function, low density lipoprotein cholesterol, serum homocysteine, and hypertension. The authors have concluded that no other preventive method would have so great an impact on public health in the Western world.

Both the proposed pill and its target population have attracted controversy. Richard Bonow of the American Heart Association said: "The usefulness of the 'polypill' is purely speculative at this point--it would have to be tested in the real world before any conclusions could be drawn." He claims that it is sending out the wrong message at a time when doctors stress the importance of a healthy lifestyle in preventing cardiovascular disease.

An end to rattling patients

Others have pointed out that many of the 750 trials analysed only included high risk populations, and that the efficacy of the drugs in low and medium risk patients is not known. Bonow also questions the "one size fits all approach" and says that some people will be undertreated, whereas in people with a low risk of cardiovascular disease the potential side effects may outweigh the benefits.

However, the authors argue that, in the Western world, the risk factors are high in everyone and any reduction is beneficial. Many of the drugs have been used for at least a decade, and consequently their side effects are well known. The use of three antihypertensives in low doses and of low dose aspirin is expected to limit side effects to 8% of users. For them, alternative formulations are suggested. All of the drugs are now off-patent, and Wald says that the cost could be less than £1 ($1.6; a1.4) a day, enabling it to be used in developing countries too.