Healthy Skepticism Library item: 1399

Warning: This library includes all items relevant to health product marketing that we are aware of regardless of quality. Often we do not agree with all or part of the contents.

Publication type: news

Rabin R.
The Pill Of The Future
Staff Writer 2003 Aug 19

Full text:

In infancy, babies routinely receive a series of vaccinations. Fluoride is added to the drinking water to prevent tooth decay. Now consider this admittedly radical regimen of preventive medicine in midlife: a daily super pill that simultaneously reduces your bad cholesterol, lowers your high blood pressure and gives you a boost of aspirin and folic acid — all together slashing your risk of cardiovascular disease.

The minute you turn 55, you’d be put on the “polypill,” no questions asked. You wouldn’t even need to see a doctor. You’d just start picking up the six-pills-in-one combo at the drug store or add it to your basket at the supermarket checkout counter.

The capsule or tablet would contain three different types of blood pressure medications at half- dose levels to minimize side effects, a drug called a statin to reduce “bad” LDL cholesterol and raise “good” HDL cholesterol, aspirin to prevent dangerous clots from forming in blood vessels and folic acid, proven to lower harmful homocysteine amino acids that can irritate blood vessels and lead to blockages in the arteries.

Sound far-fetched? Not necessarily, say Drs. Nicholas Wald and Malcolm R. Law, who put forth their proposal in the British Medical Journal early this summer. They say such mass medication of the 55-plus population could dramatically reduce the incidence of heart disease — the number one killer in both the United States and Britain.

“It’s been said that it’s unacceptable or radical or wrong or silly to advocate the whole population take this product,” Law said in a telephone interview. “But when you have something like cardiovascular disease that affects over half the population, and you don’t have very good screening tests, there’s no other way to prevent it in a big way.”

Wald and Law, London epidemiologists who analyzed 750 earlier studies of LDL cholesterol-lowering statins and combined blood pressure medications, calculated that putting everyone 55 and older on a polypill would eliminate more than 80 percent of cardiovascular disease. It would extend the lives of at least a third of the population, they predict.

While they estimate that adverse effects would occur in 8 to 15 percent of pill takers, enough to cause one or two per 100 to stop taking the hypothetical pill, fatal side effects would occur in fewer than one in 10,000.All of the components except folic acid have undergone rigorous testing and proved beneficial, the authors said, and other experts agree.

But the idea is controversial, to say the least. Richard Smith, editor of the British Medical Journal, endorsed it, saying it was the most important proposal to appear in the journal in more than 50 years. He even suggested it could make Maytag-repairmen of cardiologists and heart surgeons. “ … Keep this issue of the BMJ,” Smith wrote. “It may well become a collectors’ item.”

One day, he wrote, “We could buy the pills in supermarkets and pubs — perhaps even washing them down with a glass of red wine and preventing still more deaths.”

But skeptics, many of them clinicians, deride the proposal as an ivory-tower dream that fails to address the practical realities of treating real patients — people with disparate risk factors and medical histories, different tolerances for medication and varying predispositions and sensitivities.

“Fantasy medicine,” London physician Dr. Kaiser Chaudhrie responded to the journal article in a letter. “Pie in the sky,” another doctor wrote. “The piece should have been published in a journal of medical hypotheses,” wrote William Hoefnagels, a neurologist from the Netherlands.

John Petrie of New Zealand agreed that the journal was, indeed, “a collectors’ item — the issue has been published on a date other than … April 1st.”

In a more measured but strong statement, officials of the American Heart Association said the usefulness of a polypill is “purely speculative” and stressed that it has neither been tested in clinical trials nor been approved by any regulatory agencies, which tend to subject combination medications to rigorous scrutiny because of the risk of drug interactions.

“There is no evidence that giving an entire population over the age of 55 a magic pill would significantly reduce cardiovascular diseases,” said Dr. Robert O. Bonow, president of the American Heart Association.

The polypill could potentially pose risks to patients, Bonow and others said.

“The problem is, one size doesn’t fit all,” said Dr. Nieca Goldberg, a cardiologist in Manhattan who is spokeswoman for the American Heart Association. “Every patient is an individual, and people need different doses of blood pressure medicine and cholesterol-lowering medicine, and not everyone can tolerate aspirin.

“We need to take the lessons we learned from the Women’s Health Initiative [regarding the safety of hormone replacement therapy] and apply it to this, and the lesson is: It needs to be tested,” she said. “It needs to be tested in men, it needs to be tested in women, it needs to be tested in African-Americans, it needs to be tested in Hispanics, it needs to be tested in the elderly and in the 55-year-olds.”

The medications that would be rolled into the polypill are proven to be effective, but studies have shown that aspirin — one of the more controversial components — does not necessarily save lives when administered en masse because the drop in heart attacks and strokes is offset by an increase in deaths from bleeding complications, Bonow said. Statins are linked to rare cases of rhabdomyolysis, a breakdown of muscle cells that can be deadly. Beta blockers, a type of blood pressure-lowering drug, cannot be taken by asthmatics. And lowering blood pressure too much can cause giddiness or fainting and has resulted in falls among the elderly.

The idea of mass-medicating even healthy people is clearly anathema to many and appears to have touched a nerve in physicians, some of whom take offense to the cookbook-medicine approach. Other critics suggested that the medication model lets people off the hook about changing their behavior.

“A revolutionary step forward, or a dubious get- out-of-jail-free card for couch potatoes who would be better off mending their ways … ?” an editorial in New Scientist magazine asked of the polypill strategy.

But the proponents of the polypill are serious. Wald and Law, professors of preventive medicine at Queen Mary’s School of Medicine and Dentistry at the University of London, have filed a patent application on the formulation and applied to trademark the name Polypill.

They plan to launch random clinical control trials with an eye to getting the polypill on the market in a matter of years, Law said in a telephone interview.

The two are not the first to come up with the idea of combining preventive medications. Just days before their article was published, the U.S. Food and Drug Administration approved Bristol-Myers .Squibb’s Pravigard PAC, which packages buffered aspirin and the cholesterol drug Pravachol, or Pravastatin sodium, side-by-side in neat daily-dose packets for convenience’s sake. The two medications are often prescribed together to reduce risks of cardiovascular disease. The company is developing a combined drug that will contain both components in a single capsule, a spokeswoman said.

“When you work in this field, you become impressed with how terribly common heart disease is, because our risks are high,” said Law, who acknowledged that as a professor he does not actually treat patients. “The effect of eliminating one risk is limited, but if you eliminate several risks you can practically eliminate the risk altogether, and that leads to the idea that people should take several tablets.”

In the United States, heart disease is the leading cause of premature deaths in men from age 40 on and the second leading cause of death in women from 50 on. It is also a leading cause of severe disability.

Together, heart disease and stroke, the principal components of cardiovascular disease, are responsible for 40 percent of all deaths, killing 950,000 American a year, according to the American Heart Association. And even skeptical physicians say the polypill’s advantage would be to reach those who are most difficult to persuade of the need for prevention: people who have not yet suffered a cardiac event but may be at risk, as well as the uninsured.

Aspirin is already prescribed routinely to many men over 45, Law said. “We’re saying the same applies for cholesterol- and blood pressure-lowering drugs. They help everyone. Maybe they help some more than others, but don’t worry about it. Give it to everyone, just make sure they’re safe.”

Dr. Bertrand Bell, distinguished university professor at Albert Einstein School of Medicine in the Bronx, agrees. “Statins belong in the drinking water,” he said in an interview, not entirely facetiously, recalling that he always taught his students that “SAAB is not the name of an imported Swedish automobile but the abbreviation of the names of drugs that should be added to the drinking water: statins, ACE inhibitors, aspirin, beta blockers.”

Dr. Paul D. Thompson, chairman of the committee for prevention of the American College of Cardiology, said he is not entirely opposed to the polypill idea either, though he has reservations about including aspirin and blood pressure medications in the formula because of potential side effects. “The primary prevention recommendation is to assess someone’s overall risk … that way, you get the most bang for your treatment buck,” he said. On the other hand, this approach “cuts out a lot of the costs of screening and physician involvement.”

In two papers that are part of the trilogy published in the British Medical Journal on June 28, Wald and Law attempted to quantify the effect of the polypill by conducting large systematic reviews of hundreds of earlier studies of its separate components.

One paper described three such analyses of hundreds of studies examining the effect of statins on low density lipoprotein (LDL) cholesterol, heart disease and stroke. It concluded that statins lowered LDL cholesterol enough to reduce the risk of heart disease by 60 percent and stroke by 17 percent.

A second paper was an analysis of 354 random double-blind trials in which 40,000 patients were treated with different classes of blood pressure-lowering agents, singly and in combination: thiazides, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists and calcium channel-blockers in fixed doses.

It concluded that combining low doses of different blood pressure-lowering drugs increased the effectiveness of the medications and reduced the occurrence of side effects.

Combination drugs reduced the risk of stroke by 63 percent and reduced heart disease events by 46 percent at ages 60 to 69.

Law and Wald estimated that combining the six ingredients in a low-cost generic pill would reduce heart disease events by 88 percent and stroke by 80 percent.

But “there are no quick fixes in life or medicine, and the polypill is not one for heart disease,” Gerd Assmann, professor of medicine from Muenster, Germany, wrote in e-mail correspondence to the medical journal.

However, Law compared the polypill to a vaccination for a childhood disease that puts everyone at risk — or a prophylactic treatment during a trip to a different part of the world.

“If you go to certain countries in South America, you take an antimalarial pill,” he said. “If you live in a place where there’s a lot of heart disease, you take a tablet to keep you from getting it. It’s the same thing.”