A Remedy Off the Rack?

Often, whether it’s swinging a five-iron or making a speech, the best results come from letting go a little, lowering the bar just a touch. But could that principle extend to doctors treating patients? “At medical school, I was taught to aim for perfection,” says Anthony Rodgers, director of the clinical trials research unit at the University of Auckland. But now Rodgers and others are preparing to show that, when it comes to preventing heart attack and stroke, the way forward for doctors may be to fuss less over drugs and dosages and instead prescribe, for everyone, a single, multi-function pill.

Long debated as a concept, the polypill is ready for trial in Australia and New Zealand. A half-pink, half-white tablet manufactured by Dr. Reddy’s Laboratories in India, it contains small doses of several well-known medications: aspirin (to prevent blood clots), a statin (to lower cholesterol), and two blood-pressure-lowering agents. When two British researchers pushed the case for the polypill in a 2003 report in the British Medical Journal, they argued that if taken daily by people with vascular disease and those aged over 55, it would cut the incidence of heart attack and stroke by more than 80%. While advocates have retreated marginally from that claim, their enthusiasm is palpable. “In terms of delivering care at the community level,” says Anushka Patel, director of the cardiovascular division of Sydney’s The George Institute for International Health, “I think it’s potentially one of the most exciting advances we’ve seen for a long time.”

The task for researchers is to clarify who, eventually, should take the polypill. Separate trials in Australia (in the indigenous community) and New Zealand will involve 1,200 subjects who have had a cardiovascular event. A problem with patients in this category is that, after six months or so, many stop taking the battery of medications prescribed to prevent a second episode. Often they feel well and balk at the cost, inconvenience or stigma of popping five pills a day. But slackening off can be deadly: between a third and a half of the more than 50,000 Australians (and 11,800 New Zealanders) who die each year from cardiovascular disease have previously survived a heart attack or stroke. As a way to boost compliance, condensing treatment into a single pill, says Patel, “is probably going to be one of the biggest steps forward we can make at this stage.” The trials will pit a polypill-based strategy against standard care. The aim: to find out whether the tinkering with dosages that’s been a pillar of cardiovascular treatment—5 mg more of this, 5 mg less of that—really makes much difference. The answer is probably no, says Patel, even though “we might feel threatened as doctors by that.”

More important, she suspects, is the availability of treatment that may be less tailored but easier to stick to. In poorer countries, tailoring is virtually impossible: “getting some medication out to the people” is all that matters, says the University of Auckland’s Rodgers. The polypill will be relatively cheap because the patents on all of its components have expired. “And we know these agents work,” says Rodgers.

A trickier question is who else might eventually be encouraged to take the poly-pill. Like all drugs, each of its components carries the risk of side effects, and these have to be weighed against the potential benefits. For over-55s in excellent cardio health, the net benefit would be minimal. So another study will involve 600 subjects who doctors believe run a 7.5% to 15% risk of having a heart attack or stroke in the next five years, regardless of age. None of them will have cholesterol levels or blood pressure that would qualify them for treatment under current guidelines, just mild to moderate elevation in their readings across multiple risk factors. Treating for overall rather than individual risk recognizes the arbitrary nature of treatment thresholds and the fact that average readings don’t rule out problems.

Apart from side effects and a shift toward off-the-rack medicine, objections to the polypill are based on concerns that we’re becoming too reliant on drugs: “Walking for 45 minutes most days of the week would give the equivalent benefits of the polypill,” says Roger Allan, chairman of the clinical issues committee of Australia’s National Heart Foundation. The polypill, he says, “is the lazy man’s option.” In 2004, health experts in the Netherlands proposed the polymeal—fish, red wine, garlic, vegetables, fruit, almonds, dark chocolate—as an alternative of roughly equal potency.

In an ideal world, concedes Patel, people at risk of heart disease would change their lifestyles. In reality, most don’t. So “in the next several decades, the polypill looks like the answer.” Depending on the trial results, doctors may be prescribing it within three years. By then, staving off a deadly cardiac event could be a whole lot simpler.