Cholesterol skeptics have their day

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(Fortune) -- Is low cholesterol the pathway to a healthier heart? That's certainly what most medical experts - and their patients - have assumed for the last 30 years or so. But a recently-released study of Merck and Schering-Plough's cholesterol-lowering drug, Vytorin, is giving new voice to medical critics who have groused for decades about the questionable benefit of using medications to lower cholesterol and thereby prevent heart disease.

On January 14th, after a long delay, Merck and Schering-Plough unveiled results of their so-called ENHANCE study, an investigation into whether their co-marketed statin, Vytorin was able to not only lower "LDL" or "bad" cholesterol, but by doing so, clear patients' arteries of plaque.

The results of the 720-patient trial were surprising. In the end, researchers found that Vytorin, a combination pill that melds Schering's Zetia with Merck's Zocor, was no better at slowing the build up of fatty plaques in the arteries than a generic cholesterol pill alone. That could have profound implications for the two firms, and for the drug industry at large.

Not everyone was surprised, however. A small, vocal cadre of medical experts has always questioned the efficacy of cholesterol-lowering drugs. Take, for instance, Dr. John Abramson, a clinical instructor at Harvard Medical School, and author of "Overdosed America: The Broken Promise of American Medicine." For years, Abramson has railed against the drug industry for pushing what he labels "the myth that lowering cholesterol with drugs is the most effective way to prevent heart disease."

Abramson believes that using a statin - a treatment that stimulates the liver's low-density lipoprotein (LDL) receptors to clear more LDL from the bloodstream - to reduce cholesterol levels can be beneficial, but only for patients who have heart disease or diabetes (or for men under age 65 who are at high risk, through factors like weight or family history). But for many people who take statins, Abramson claims, there is no evidence the drugs are beneficial.

"American doctors, and the public, have been duped," he says. "These drugs have been on the market for 21 years; they are the best-selling drug class in history. And yet there is still not a single study that documents a health benefit to women of any age or men over 65 who don't already have heart disease or diabetes."

Abramson is not alone. Peter Langsjoen, a cardiologist at East Texas Medical Center in Tyler, Texas only prescribes cholesterol-lowering drugs in rare cases. Sure, statins lower cholesterol, says Langsjoen, but low cholesterol isn't the pathway to Nirvana, he insists. It's just a number. "We've created cholesterol neurosis," jokes Langsjoen. "It's a sham based on an attractive theory. But once you explain to patients that their ancestors who ate lard and bacon and eggs every morning were awfully darn healthy, they get it. It's because they were more active."

The critique - while controversial - has been around for years. In one particularly noteworthy study conducted in Lyon, France, during the 1990s, heart attack sufferers who were counseled to eat a Mediterranean-style diet (that is, 5 servings of fruits and vegetables, more whole grains, olive oil and fish, and less red meat, butter, fatty cheeses and egg yolks) had significantly less risk of recurrent heart attack or death. That healthier diet showed two-to-three times more benefit than is achieved by taking statins in a similar context. Surprisingly, patients in the Lyon Diet Study achieved these benefits without reducing their cholesterol levels at all. The study was deemed so important by the American Heart Association that it issued a public advisory about it in 2000.

In another study - known as PROSPER - sponsored by Bristol-Myers Squibb (BMY, Fortune 500) and published in 2002, subjects over age 70 who are at high risk but don't yet have heart disease saw no benefit from taking a statin. Of all people taking statins, those with and without heart disease, PROSPER suggests there was no longevity benefit from taking a statin.

If this line of reasoning is true, it represents an economic earthquake for the pharmaceutical companies, and raises a series of troubling questions. Anti-cholesterol drugs are a $36 billion segment of the world's second-most profitable legal industry behind Big Oil. Roughly, 19 million American adults take a cholesterol-lowering medicine of some kind. And according the most recent National Cholesterol Education guidelines - the suggestions most doctors adhere to - about 36 million Americans should be on some form of statin therapy.

But equally important: If statins aren't the wonder drug that's been claimed for decades, how did doctors get it so wrong? The national guidelines state that use of a statin to reduce LDL cholesterol is recommended for people at high or moderately-high risk of heart disease. People in the high-risk group should aim for a LDL cholesterol count of less than 70 mg/dL, and those in the moderately high-risk group should have a count between 129 and 100 mg/dL.

The guidelines were published by the National Cholesterol Education Program (NCEP), a branch of NIH's National Heart, Lung, and Blood Institute. Critics of the drug industry claim that the guidelines themselves are biased toward drug therapy because a majority of the medical experts who drew up those suggestions have financial relationships with drug companies. It's no secret that academic researchers receive funding from industry in the form of grants, paid consultancies, and the like. In fact, the biotech and pharma industries fund more than 60% of biomedical research in the U.S., up from 32% in 1980.

"There's a mountain of evidence that shows that people who have financial relationships with industry produce biased research and come up with biased recommendations for treatment," notes Shannon Brownlee, author of "Overtreated: Why Too Much Medicine is Making Us Sicker and Poorer". Brownlee points out, as has been widely reported, that of the nine medical experts who devised the national cholesterol guidelines, six had received research grants, speaking honoraria, or consulting fees from at least three of the five companies that produce brand-name statins.

James Cleeman, the program's coordinator, doesn't dispute that the guidelines were drawn up by doctors who receive money from drug companies. However, he disagrees with the charge that the nation's cholesterol guidelines were fashioned by compromised experts. "In many cases, these are incidental relationships that did not influence our guidelines," Cleeman says. "The idea that lowering cholesterol is irrelevant is not correct,"he continues. "Half of men and one-third of women in the U.S. will get heart disease. You will see more heart attacks over time averted by lowering LDL cholesterol."

Another question - the ENHANCE trial ended in April of 2006. Why are the results just trickling out now? Federal and state regulators are asking the same thing, as they look into Merck (MRK, Fortune 500) and Schering-Plough's (SGP, Fortune 500) Vytorin marketing claims. The companies have said they acted in good faith in conducting the trial and communicating the results. "Merck and Schering stand behind the safety and efficacy of Vytorin," says Merck spokesperson Amy Rose.

As with so much health science, it may be years before doctors and patients receive more data on just how useful it is to reduce cholesterol - and even then it may not be definitive. For their part, Merck and Schering are touting a closely-watched 10,000-patient study known as IMPROVE-IT. That study, however, isn't expected to end until sometime in 2011.