Heart attacks, stroke, and other preventable cardiovascular diseases kill or seriously affect many populations. Western diet and lifestyle increase levels of risk factors and their combined effects have made these diseases common. Cardiovascular disease can be avoided or delayed, but the necessary changes to Western diet and lifestyle are not practicable in the short term. Randomized trials show that drugs to lower three risk factors - low density lipoprotein (LDL) cholesterol, blood pressure, and platelet function (with aspirin) - reduce the incidence of ischaemic heart disease (IHD) events and stroke. Evidence that lowering serum homocysteine (with folic acid) reduces the risk of these diseases is largely observational but still compelling.

With this in mind, a meta-analysis has recently been carried out in the United Kingdom (1) to determine the combination of drugs and vitamins to achieve prevention of cardiovascular disease with minimal adverse effects as a single daily polypill (2). The strategy would simultaneously reduce four cardiovascular risk factors: low-density lipoprotein cholesterol, blood pressure, serum homocysteine, and platelet function, regardless of pretreatment levels.

The following polypill formulations are proposed:

• a statin: e.g. atorvastatin or simvastatin;

• three blood pressure lowering drugs: e.g. a thiazide, beta blocker, and angiotensin converting enzyme (ACE) inhibitor;

• folic acid; and

• aspirin.

The polypill is estimated to reduce IHD events by 88% and stroke by 80%. One-third of people taking this pill from age 55 would therefore benefit - gaining on average about 11 years of life free from an IHD event or stroke. Summing the adverse effects of the components observed in randomized trials showed that the polypill would cause symptoms in 8-15% of people depending on the precise formulation. The authors propose that this strategy could largely prevent heart attacks and stroke if taken by everyone aged 55 and older and everyone with existing cardiovascular disease. It would be acceptably safe and with widespread use would have a greater impact on the prevention of disease in the Western world than any other single intervention.

A large preventive effect would require intervention in everyone at increased risk irrespective of the risk factor levels; intervention on several reversible causal risk factors together; and reducing these risk factors by as much as possible.

A low-cost polypill could use generic components that are no longer subject to patent protection. This formulation does not have the lowest rate of adverse effects, but even if about 10% of people were intolerant of the formulation it would still have considerable public health merit. Those found to be intolerant could be prescribed alternatives to avoid the side effects. Controlled trials of different formulations of the polypill would provide direct estimates of acceptability.

The preventive strategy outlined is radical. But the authors argue that a formulation that prevented all cancer and was safe would undoubtedly be widely used, and one that prevented more than 80% of cardiovascular disease would be even more important because such deaths are more common than cancer deaths. It is also pointed out that in Western society the risk factors are high and everyone is at risk. The diseases they cause are common and often fatal and there is much to gain and little to lose by the widespread use of these drugs. No other preventive method would have so great an impact on public health in the Western world.

Reference:

1. Law, M.R., Wald, N.J., Rudnicka, A.R. Quantifying effect of statins on low density lipoprotein cholesterol ischaemic heart disease, and stroke: systematic review and meta-analysis. British Medical Journal, 326: 1423 (2003).

2. Wald, N.J., Law, M.R. A strategy to reduce cardiovascular disease by more than 80%. British Medical Journal, 326: 1419-1422 (2003).