Polypills for the People

A tablet combining six drugs could avert deaths from heart disease and stroke, but some experts balk at the notion of putting prevention in a pill, particularly when similar benefits could be attained from a healthy diet.

When British researchers declared they had devised a pill that could make "a greater impact on the prevention of disease in the Western world than any other known intervention," they met stern opposition. The researchers' idea was simple: Bring together in a single pill several drugs that slice the risk of heart attacks and strokes, give the pill to everyone at risk for these conditions, and voilà, the number of deaths drops. But many public health experts questioned the wisdom of medicating mostly healthy people. Now, Dutch researchers have joined the skeptics with a claim that people can eat their way to similar results.

Nicholas Wald, a public health expert at the Wolfson Institute of Preventive Medicine in London, initially proposed the so-called polypill two years ago in the British Medical Journal (BMJ). Wald's polypill would contain six medications: aspirin to make the blood less sticky, a cholesterol-reducing statin, low doses of three blood pressure-lowering drugs, and folic acid to reduce blood concentrations of homocysteine, a molecule that studies have linked to heart disease risk. Doctors would prescribe the polypill for anyone with existing cardiovascular disease, diabetics over the age of 30, and people older than 55, says Wald.

After pooling previous clinical trial results for each of the six drugs, Wald and his co-author at the Wolfson Institute, Malcolm Law, concluded that the polypill would reduce deaths from heart disease and stroke by more than 80%. In the over-55 group alone, Wald and Law estimate that one-third of the individuals taking the polypill would gain an average of about 11 years free from heart attack or stroke.

Unintended consequences are a concern with any drug. But the medications included in the polypill have been on the market for several decades, so such a formulation probably wouldn't turn up many unanticipated side effects, says Anthony Rodgers of the University of Auckland, New Zealand, who wrote an editorial that accompanied the polypill paper. Several of the drugs in the polypill formula would be used at lower than standard doses, which should lessen the risk of side effects, says Wald. But just to be safe, "introduction of the polypill will probably be done with a system of reporting adverse effects in place," he says.

Even with such safeguards, most people receiving the polypill would not derive any benefit because the formula targets risk factors that provoke only a subset of heart problems and strokes. Some critics question the ethics of giving a drug to people without symptomatic disease, knowing that two-thirds of them will derive no benefit and some will experience unpleasant or even dangerous side effects. A polypill might also give people a false sense of security, discouraging them from adopting a healthy lifestyle, the critics say. Vasan Ramachandran, a physician at Boston University School of Medicine, has calculated that even if the polypill could reduce the risk of disease by 80%, 33 men with borderline risk factors would need to be treated for 5 years for one to see a benefit, and that number is even higher for women.

Furthermore, only a small portion of heart problems--one-sixth in men and one-tenth in women--occur before age 55, and most of these would not be prevented by the polypill, says Ramachandran. His research shows that the borderline risk factors targeted by the polypill, such as slightly elevated cholesterol concentrations, account for only about one-tenth of coronary disease. But Wald says such a scheme is ethically acceptable "if you cannot tell in advance that [people] will not benefit, and the expected preventive benefit is large while the risk of harm is small."

Wald's paper generated considerable controversy, with some experts objecting to promoting a pharmaceutical solution to a problem that lifestyle changes could alter just as effectively. In BMJ's annual Christmas parody issue, Oscar Franco, an epidemiologist at Erasmus University Medical Centre in Rotterdam, the Netherlands, proposed an alternative to the polypill: the "polymeal." The polymeal consists of seven foods shown in randomized trials to reduce the risk of heart disease: fish, dark chocolate, fruits, vegetables, garlic, almonds, and wine. Using the same analytical methods as the polypill authors, Franco and his colleagues showed that the polymeal combination of food and drink could reduce cardiovascular disease by about 76%. The upshot: an additional 6.6 years of life expectancy. Better yet, the polymeal could reduce risk in all adults, without drugs and with only minor side effects, such as garlic breath.

Wald says the polymeal paper "is full of entertaining comments that are obviously not intended to be taken seriously." But Rodgers says that despite the tongue-in-cheek tone of the polymeal paper, "the basic point is very sensible: Healthy diet can reduce cardiovascular disease substantially." Rodgers says there's no reason why the polypill and polymeal couldn't be used in combination to drive disease risk even lower. In that sense, Wald agrees. He says that the polypill should be just one component of a disease-prevention program: "The polypill should be used together with a sensible diet, weight control, and the avoidance of smoking--not as a substitute."

Whether the polypill would catch on remains uncertain. For many people, the polypill might be a more convenient formulation of drugs they currently use, says Wald: "Many elderly people are already taking many of the components of the polypill as separate pills." Others might be reluctant to take medication, especially when they're not sick.

Cost might also be an issue. Wald suggests that the polypill might cost in the range of $2 per dose, or $60 per month. That's cheaper than the polymeal, which Franco calculated would run about $30 per week, although many people might already spend that much on food. But the polymeal still might enjoy an advantage, says Franco. Strawberries, wine, and chocolate are a lot tastier than any pill.

Christie Aschwanden is a freelance writer who adopted the polymeal before she knew it was good for her.