For the past four decades, we've been told to stay away from red meat, dairy and cheese -- foods high in saturated fats -- because saturated fat is bad for the heart.
But investigative reporter Nina Teicholz says that isn't the case...
When we translate our ideas to the print medium, the output gets longer, gets edited and gets read by different readers. Here's our guest column from our local Jewish newspaper of record, the Jewish Standard.Cheerios and the future of Judaism in America
Tzvee Zahavy • Columns
Published: 15 May 2009
When we say that we aspire to live the talmudic life, that means two things.
First, it means that we question rigorously all those facts and influences around us. We especially separate our certainties from our doubts.
Guest column
And second, it means that we live in constant touch and tension with our present world to which we can respond and sometimes over which we can exercise some control. A good talmudist does not pretend to have dominion over the unknown future.
OK, what do Cheerios have to do with the future of Judaism in America? ...more...
Under the do-nothing George Bush FDA, anybody could claim anything and nobody would say a word.U.S. objects to General Mills' Cheerios health claims
WASHINGTON (Reuters) - General Mills made unauthorized health claims about the heart-related benefits of its Cheerios Toasted Whole Grain Oat Cereal, U.S. regulators said in a letter released on Tuesday.
The U.S. Food and Drug Administration said it considered language about cholesterol-lowering on Cheerios boxes to be unapproved drug claims. The language did not qualify under the government's approved claims associating fiber from whole grain oats with reduced risk of heart disease, the May 5 letter said.
General Mills officials were not immediately available for comment.
Yes, according to the article in today's Times, the Harvard University Medical School is a corrupt entity.Harvard Medical School in Ethics Quandary
By DUFF WILSON
BOSTON — In a first-year pharmacology class at Harvard Medical School, Matt Zerden grew wary as the professor promoted the benefits of cholesterol drugs and seemed to belittle a student who asked about side effects.
Mr. Zerden later discovered something by searching online that he began sharing with his classmates. The professor was not only a full-time member of the Harvard Medical faculty, but a paid consultant to 10 drug companies, including five makers of cholesterol treatments.
“I felt really violated,” Mr. Zerden, now a fourth-year student, recently recalled. “Here we have 160 open minds trying to learn the basics in a protected space, and the information he was giving wasn’t as pure as I think it should be.”
Mr. Zerden’s minor stir four years ago has lately grown into a full-blown movement by more than 200 Harvard Medical School students and sympathetic faculty, intent on exposing and curtailing the industry influence in their classrooms and laboratories, as well as in Harvard’s 17 affiliated teaching hospitals and institutes.
They say they are concerned that the same money that helped build the school’s world-class status may in fact be hurting its reputation and affecting its teaching.
The students argue, for example, that Harvard should be embarrassed by the F grade it recently received from the American Medical Student Association, a national group that rates how well medical schools monitor and control drug industry money.
Harvard Medical School’s peers received much higher grades, ranging from the A for the University of Pennsylvania, to B’s received by Stanford, Columbia and New York University, to the C for Yale... more racketeering news...
He didn't invent the artificial heart. He doesn't row. He is not licensed to practice medicine. In the pfake Pfizer ads, Jarvik sure looked like an expert that we should trust. He said to take Lipitor to prevent heart attack - so we must do that!Pfizer to End Lipitor Campaign by Jarvik
By STEPHANIE SAUL
Under criticism that its ads are misleading, Pfizer said Monday it would cancel a long-running advertising campaign using the artificial heart pioneer Dr. Robert Jarvik as a spokesman for its cholesterol drug Lipitor.
Pfizer has spent more than $258 million advertising Lipitor since January 2006, most of it on the Jarvik campaign, as the company sought to protect Lipitor, the world’s best-selling drug, from competition by cheaper generics.
But the campaign had come under scrutiny from a Congressional committee that is examining consumer drug advertising and has asked whether the ads misrepresented Dr. Jarvik and his credentials. Although he has a medical degree, Dr. Jarvik is not a cardiologist and is not licensed to practice medicine.
One television ad depicted Dr. Jarvik as an accomplished rower gliding across a mountain lake, but the ad used a body double for the doctor, who apparently does not row.
“The way in which we presented Dr. Jarvik in these ads has, unfortunately, led to mis-impressions and distractions from our primary goal of encouraging patient and physician dialogue on the leading cause of death in the world — cardiovascular disease,” Pfizer’s president of worldwide pharmaceutical operations, Ian Read, said in a statement. “We regret this. Going forward, we commit to ensuring there is greater clarity in our advertising regarding the presentation of spokespeople.”
A company spokeswoman, Vanessa Aristide, said Pfizer was working with its advertising agency, the Kaplan Thaler Group, to develop a new campaign.
Lipitor, with sales of $12.7 billion last year, is protected by patent until 2010. Some patients have, nevertheless, begun switching to a generic version of a competing cholesterol drug, Zocor.
The House Energy and Commerce Committee has been looking into television ads featuring Dr. Jarvik. The committee disclosed that Pfizer agreed to pay Dr. Jarvik at least $1.35 million under a two-year contract that expired next month. John D. Dingell, the Michigan Democrat who is chairman of that committee, raised questions about Dr. Jarvik’s credentials to recommend Lipitor.
Dr. Jarvik, who has recently declined to discuss the Lipitor campaign, could not be reached for comment Monday.
The committee’s investigation has rekindled a debate over the so-called direct-to-consumer advertising of pharmaceuticals, a $4.8 billion business. Mr. Dingell and Bart Stupak, another Michigan Democrat who heads an investigations subcommittee, applauded Pfizer’s decision to pull the Lipitor ads.
“I commend Pfizer for doing the right thing and pulling the Lipitor ads featuring Dr. Jarvik,” Mr. Stupak said in a statement. “When consumers see and hear a doctor endorsing medication, they expect the doctor is a credible individual with requisite knowledge of the drug.”
While endorsing Pfizer’s decision, the committee showed no sign of shutting down its investigation. Mr. Stupak said the committee planned to meet with Dr. Jarvik and collect all of the documents it had requested.
The committee had recently asked 10 advertising agencies that worked on the Dr. Jarvik campaign to submit documents about the use of body doubles. The committee has also contacted at least one former colleague of Dr. Jarvik’s who contends that he was not the actual inventor of the artificial heart, as stated in the ads.
In a letter to Pfizer in August 2006, three former colleagues of Dr. Jarvik’s at the University of Utah complained that the ads erroneously identified Dr. Jarvik as “inventor of the artificial heart.” That distinction, they said, should go to Dr. Jarvik’s mentor, Dr. Willem J. Kolff, and his associate, Dr. Tetsuzo Akutsu.
Pfizer subsequently changed its ads to identify Dr. Jarvik as the inventor of the “Jarvik artificial heart,” but Dr. Jarvik’s former colleagues, members of a large team that worked on the heart, were not entirely satisfied, according to Dr. Donald B. Olsen, a veterinarian who worked on the heart and is president of the Utah Artificial Heart Institute. Dr. Olsen said he was recently contacted by the committee.
A long-simmering dispute over assigning credit for the artificial heart boiled over again during a conference last December at the University of Utah. Dr. Jarvik did not attend the conference, which marked the 25th anniversary of the heart’s experimental use to extend the life of Dr. Barney Clark, a Seattle dentist.
During the meeting, another former Utah colleague of Dr. Jarvik’s, Dr. Clifford S. Kwan-Gett, stated that the Jarvik series of hearts were simply different versions of prototypes that Dr. Kwan-Gett had made more than a year earlier.
Dr. Jarvik’s company, Jarvik Heart, subsequently posted a history of the artificial heart’s development on its Web site, giving his own account of the heart’s development. That posting said Dr. Jarvik’s design overcame two problems of the heart developed by Dr. Kwan-Gett.
Jarvik Heart, based in Manhattan, has been working for the last two decades on a continuous flow pump that can be inserted directly into a patient’s damaged heart to bolster its function.
In the wake of the distressing news about the uselessness of anti-cholesterol drugs, this study is not good news for drug companies. This is not good news for people with depression. This is good news I guess for class-action-lawyers.Depression drugs don’t work, finds data review
David Rose
Millions of people taking commonly prescribed antidepressants such as Prozac and Seroxat might as well be taking a placebo, according to the first study to include unpublished evidence.
The new generation of antidepressant drugs work no better than a placebo for the majority of patients with mild or even severe depression, comprehensive research of clinical trials has found.
The researchers said that the drug was more effective than a placebo in severely depressed patients but that this was because of a decreased placebo effect.
The study, described as “fantastically important” by British experts, comes as the Government publishes plans to help people to manage depression without popping pills.more...
Do the cholesterol drugs do any good for your health? We've seen this issue challenged after a scandal involving suppression of a drug study of Vytorin.
There are some indications that statins aren’t all they’re cracked up to be.
Like the drug ads say, the Vytorin scandal has two causes: (1) who your ancestors are, i.e., all the people at Merck and Schering-Plough who hid the study on its ineffectiveness for two years, and (2) what you eat, i.e., the fact that cholesterol levels may have little or nothing to do with heart disease.The truth is, we’ve always had reason to question the idea that cholesterol is an agent of disease. Indeed, what the Framingham researchers meant in 1977 when they described LDL cholesterol as a “marginal risk factor” is that a large proportion of people who suffer heart attacks have relatively low LDL cholesterol.Although I am pleased that the broad issue is getting attention, I am disappointed that the nasty cover up by Merck and Schering-Plough has receded into the background.
Are you taking Zetia or Vytorin?Well that clears up the "confusion" -- NOT!
If so, you may be worried about recent news stories questioning the benefit of these medicines... on the basis of a single study that has generated a lot of confusion.
In fact, ZETIA and VYTORIN (capitals supplied by advertiser) have been proven to lower LDL (bad) cholesterol along with diet in multiple clinical studies involving thousands of patients...
All of us at Merck and Schering-Plough proudly stand behind the established efficacy and safety profiles of ZETIA and VYTORIN (capitals supplied by advertiser).
In fact, ZETIA and VYTORIN (capitals supplied by advertiser) have been proven to lower LDL (bad) cholesterol along with diet...The correct syntax of this sentence would reveal to us that diet is at least as important as drugs in lowering cholesterol:
In fact, along with diet, ZETIA and VYTORIN (capitals supplied by advertiser) have been proven to lower LDL (bad) cholesterol ...One last thing. The ad uses terms like "multiple," "thousands," and of course, "all of us..." - "All of us at Merck and Schering-Plough proudly stand behind..."
Vytorin Ad Shame Taints Entire Marketing Industry
Cholesterol Drug's Ad Campaign Turns Into PR Nightmare, Fanning Flames of Public Mistrust of DTC
By Rich Thomaselli
CHARLOTTE, N.C. (AdAge.com) -- The video shows the oh-so-familiar commercial for cholesterol drug Vytorin, in which benign-looking "aunts" and "uncles" are dressed up to look like platefuls of fatty foods. What's different, however, is the voice-over: "Nobody knows if Vytorin is safe or effective, but with enough scientific fraud, we can sure make it looks like it is," says the narrator in the YouTube parody.....
Forbes has an excellent article reviewing the situation called, "The Vytorin Consensus."Companies Pull TV Ads for Vytorin
NEWARK, N.J. (AP) — Merck & Co. and Schering-Plough Corp. said Tuesday they have suspended TV ads for Vytorin, a week after a study revealed the cholesterol drug is no more effective than a high dose of one of its components available generically at a third of the cost.
Vytorin, developed by Merck and Schering-Plough, is a combination of Zetia and Merck's Zocor, which lost patent protection in 2006.
The companies market Zetia and Vytorin jointly and split the profits. Shares of both companies fell Tuesday.
The ads tell viewers that about the genetic and dietary causes of high cholesterol — "food and family" — and show "family members" interspersed with food.
Ads have also been pulled for Zetia, said Skip Irvine, a spokesman for Merck/Schering-Plough Pharmaceuticals.
"We've made the decision to voluntarily and temporarily suspend direct-to-consumer broadcast advertising in light of mischaracterization and misinterpretation of the enhanced trial results," he said, declining to elaborate or comment on the data.
However, he said print ads will continue.
The study of 720 patients was meant to show how well Vytorin reduced plaque buildup in neck arteries in people whose genes gave them stratospheric cholesterol.
Instead, it showed $100-a-month Vytorin was no more effective and perhaps a bit worse than Zocor alone, which is sold as a generic for a third as much.
Cover Story January 17, 2008
Do Cholesterol Drugs Do Any Good?
Research suggests that, except among high-risk heart patients, the benefits of statins such as Lipitor are overstated
Martin Winn's cholesterol level was inching up. Cycling up hills, he felt chest pain that might have been angina. So he and his doctor decided he should be on a cholesterol-lowering medication called a statin. He was in good company. Such drugs are the best-selling medicines in history, used by more than 13 million Americans and an additional 12 million patients around the world, producing $27.8 billion in sales in 2006. Half of that went to Pfizer (PFE) for its leading statin, Lipitor. Statins certainly performed as they should for Winn, dropping his cholesterol level by 20%. "I assumed I'd get a longer life," says the retired machinist in Vancouver, B.C., now 71. But here the story takes a twist. Winn's doctor, James M. Wright, is no ordinary family physician. A professor at the University of British Columbia, he is also director of the government-funded Therapeutics Initiative, whose purpose is to pore over the data on particular drugs and figure out how well they work. Just as Winn started on his treatment, Wright's team was analyzing evidence from years of trials with statins and not liking what it found.
Yes, Wright saw, the drugs can be life-saving in patients who already have suffered heart attacks, somewhat reducing the chances of a recurrence that could lead to an early death. But Wright had a surprise when he looked at the data for the majority of patients, like Winn, who don't have heart disease. He found no benefit in people over the age of 65, no matter how much their cholesterol declines, and no benefit in women of any age. He did see a small reduction in the number of heart attacks for middle-aged men taking statins in clinical trials. But even for these men, there was no overall reduction in total deaths or illnesses requiring hospitalization—despite big reductions in "bad" cholesterol. "Most people are taking something with no chance of benefit and a risk of harm," says Wright. Based on the evidence, and the fact that Winn didn't actually have angina, Wright changed his mind about treating him with statins—and Winn, too, was persuaded. "Because there's no apparent benefit," he says, "I don't take them anymore."
Wait a minute. Americans are bombarded with the message from doctors, companies, and the media that high levels of bad cholesterol are the ticket to an early grave and must be brought down. Statins, the message continues, are the most potent weapons in that struggle. The drugs are thought to be so essential that, according to the official government guidelines from the National Cholesterol Education Program (NCEP), 40 million Americans should be taking them. Some researchers have even suggested—half-jokingly—that the medications should be put in the water supply, like fluoride for teeth. Statins are sold by Merck (MRK) (Mevacor and Zocor), AstraZeneca (AZN) (Crestor), and Bristol-Myers Squibb (BMY) (Pravachol) in addition to Pfizer. And it's almost impossible to avoid reminders from the industry that the drugs are vital. A current TV and newspaper campaign by Pfizer, for instance, stars artificial heart inventor and Lipitor user Dr. Robert Jarvik. The printed ad proclaims that "Lipitor reduces the risk of heart attack by 36%...in patients with multiple risk factors for heart disease."
So how can anyone question the benefits of such a drug?
For one thing, many researchers harbor doubts about the need to drive down cholesterol levels in the first place. Those doubts were strengthened on Jan. 14, when Merck and Schering-Plough (SGP) revealed results of a trial in which one popular cholesterol-lowering drug, a statin, was fortified by another, Zetia, which operates by a different mechanism. The combination did succeed in forcing down patients' cholesterol further than with just the statin alone. But even with two years of treatment, the further reductions brought no health benefit.
DOING THE MATH
The second crucial point is hiding in plain sight in Pfizer's own Lipitor newspaper ad. The dramatic 36% figure has an asterisk. Read the smaller type. It says: "That means in a large clinical study, 3% of patients taking a sugar pill or placebo had a heart attack compared to 2% of patients taking Lipitor."
Now do some simple math. The numbers in that sentence mean that for every 100 people in the trial, which lasted 3 1/3 years, three people on placebos and two people on Lipitor had heart attacks. The difference credited to the drug? One fewer heart attack per 100 people. So to spare one person a heart attack, 100 people had to take Lipitor for more than three years. The other 99 got no measurable benefit. Or to put it in terms of a little-known but useful statistic, the number needed to treat (or NNT) for one person to benefit is 100.
Compare that with, say, today's standard antibiotic therapy to eradicate ulcer-causing H. pylori stomach bacteria. The NNT is 1.1. Give the drugs to 11 people, and 10 will be cured.
A low NNT is the sort of effective response many patients expect from the drugs they take. When Wright and others explain to patients without prior heart disease that only 1 in 100 is likely to benefit from taking statins for years, most are astonished. Many, like Winn, choose to opt out.
Plus, there are reasons to believe the overall benefit for many patients is even less than what the NNT score of 100 suggests. That NNT was determined in an industry-sponsored trial using carefully selected patients with multiple risk factors, which include high blood pressure or smoking. In contrast, the only large clinical trial funded by the government, rather than companies, found no statistically significant benefit at all. And because clinical trials themselves suffer from potential biases, results claiming small benefits are always uncertain, says Dr. Nortin M. Hadler, professor of medicine at the University of North Carolina at Chapel Hill and a longtime drug industry critic. "Anything over an NNT of 50 is worse than a lottery ticket; there may be no winners," he argues. Several recent scientific papers peg the NNT for statins at 250 and up for lower-risk patients, even if they take it for five years or more. "What if you put 250 people in a room and told them they would each pay $1,000 a year for a drug they would have to take every day, that many would get diarrhea and muscle pain, and that 249 would have no benefit? And that they could do just as well by exercising? How many would take that?" asks drug industry critic Dr. Jerome R. Hoffman, professor of clinical medicine at the University of California at Los Angeles.
Drug companies and other statin proponents readily concede that the number needed to treat is high. "As you calculated, the NNT does come out to about 100 for this study," said Pfizer representatives in a written response to questions. But statin promoters have several counterarguments. First, they insist that a high NNT doesn't always mean a drug shouldn't be widely used. After all, if millions of people are taking statins, even the small benefit represented by an NNT over 100 would mean thousands of heart attacks are prevented.
That's a legitimate point, and it raises a tough question about health policy. How much should we spend on preventative steps, such as the use of statins or screening for prostate cancer, that end up benefiting only a small percentage of people? "It's all about whether we think the population is what matters, in which case we should all be on statins, or the individual, in which case we should not be," says Dr. Peter Trewby, consultant physician at Darlington Memorial Hospital in Britain. "What is of great value to the population can be of little benefit to the individual." Think about buying a raffle ticket for a community charity. It's for a good cause, but you are unlikely to win the prize.
Statin proponents also argue that when NNTs are calculated after the drugs have been taken for just three or five years, they're misleadingly high. Pfizer says that even though only one heart attack was prevented per 100 people in its trial, "it may be a possibility that several or even all [100] benefit" by reducing their risk of a future heart attack. And the benefit grows when the drugs are taken for more years, backers believe. "It does not make sense to take a statin for five years," says Dr. Scott M. Grundy, chair of the NCEP committee that called for more aggressive statin treatment and director of the Center for Human Nutrition at the University of Texas Southwestern Medical Center at Dallas. "When you take a cholesterol-lowering drug, it is a huge commitment," he says. "You take it for life." Grundy figures the chances of having a heart attack over the course of a lifetime are about 30% to 50% (higher for men than women). Statins, he argues, reduce that risk by about 30%. As a result, taking the drugs for 30 years or more would bring 9 to 15 fewer heart attacks for every 100 people. So only 7 to 11 people would have to take the drugs for life for one to benefit.
Critics reply that this rosier picture requires several leaps of faith. A 30% reduction in heart attacks "is the best-case scenario and not found in many of the studies," says Wright. What's more, statins have been in use now for 20 years, and there's little evidence yet that the NNT decreases the longer people take the drug. Most important, the statin trials of people without existing heart disease showed no reduction in deaths or serious health events, despite the small drop in heart attacks. "We should tell patients that the reduced cardiovascular risk will be replaced by other serious illnesses," says Dr. John Abramson, clinical instructor at Harvard Medical School and author of Overdosed America.
LIFESTYLE CHANGES
In its written response, Pfizer did not challenge this key assertion: that the drugs do not reduce deaths or serious illness in those without heart disease. Instead, the company repeated that statins reduce the "risk of death from coronary events" and added that Wright's analysis was not published in a peer-reviewed scientific journal.
If we knew for sure that a medicine was completely safe and inexpensive, then its widespread use would be a no-brainer, even with a high NNT of 100. But an estimated 10% to 15% of statin users suffer side effects, including muscle pain, cognitive impairments, and sexual dysfunction. And the widespread use of statins comes at the cost of billions of dollars a year, not just for the drugs but also for doctors' visits, cholesterol screening, and other tests. Since health-care dollars are finite, "resources are not going to interventions that might be of benefit," says Dr. Beatrice A. Golomb, associate professor of medicine at the University of California at San Diego School of Medicine.
What would work better? Perhaps urging people to switch to a Mediterranean diet or simply to eat more fish. In several studies, both lifestyle changes brought greater declines in heart attacks than statins, though the trials were too small to be completely persuasive. Being physically fit is also important. "The things that really work are lifestyle, exercise, diet, and weight reduction," says UCLA's Hoffman. "They still have a big NNT, but the cost is much less than drugs and they have benefits for quality of life."
Difficult risk-benefit questions surround most drugs, not just statins. One dirty little secret of modern medicine is that many drugs work only in a minority of people. "There's a tendency to assume drugs work really well, but people would be surprised by the actual magnitude of the benefits," says Dr. Steven Woloshin, associate professor of medicine at Dartmouth Medical School.
A good example: Beta-blockers are seen as essential in treating congestive heart failure. Yet studies show that an average of 24 people must take the drugs for seven months to prevent one hospitalization from heart failure (thus, an NNT of 24). And 40 people must take it to prevent one death (NNT of 40). "Even for medications we consider effective, we see NNTs in the 20s or higher," says Dr. Henry C. Barry, associate professor of family medicine at Michigan State University College of Human Medicine.
For many other drugs, the NNTs are large. Take Avandia, GlaxoSmithKline's (GSK) drug for preventing the deadly progression of diabetes. The blockbuster, with $2.6 billion in U.S. sales in 2006, made headlines in 2007 when an analysis of clinical trial data showed it increased the risk of heart attacks. The largely untold story: There's little evidence the drug actually helps patients. Yes, Avandia is very good at lowering blood sugar, just as statins lower cholesterol levels. But that doesn't translate into preventing the dire consequences of diabetes, including heart disease, strokes, and kidney failure. Clinical trials "failed to find a significant reduction in cardiovascular events even with excellent glucose control," wrote Dr. Clifford J. Rosen, chair of the Food & Drug Administration committee that evaluated Avandia, in a recent commentary in The New England Journal of Medicine. "Avandia is almost the poster child for everything wrong with our system," says UCLA's Hoffman. "Its NNT is close to infinite."
Regarding Avandia, Dr. Murray Stewart, Glaxo's vice-president for clinical development, says that the evidence of its benefits against heart disease and other major complications of diabetes "is still inconclusive." But the drug has other benefits, he argues, such as delaying the need to take insulin.
When other medications widely believed to be effective were put to the test of a clinical trial, they flunked. Hormone replacement therapy didn't protect against heart disease. Anti-psychotic drugs were actually less effective than a placebo in reducing aggression in patients with intellectual disability.
The truth about drugs' effectiveness wouldn't be as worrisome if consumers and doctors had an accurate picture of the state of knowledge and could make rational decisions about treatments. Studies by Darlington Hospital's Trewby, UBC's Wright, and others, however, show that patients expect far more than what the drugs actually deliver.
Why the mismatch? Some of the blame goes to the way results are presented. A 36% decline in heart attacks sounds more dramatic and important than an NNT of 100. "It comes as a shock to see the NNT," says Dr. Barnett S. Kramer, director of the office of medical applications of research at the National Institutes of Health. Drug companies take full advantage of this; they advertise the big percentage drops in, say, heart attacks, while obscuring the NNT. But when it comes to side effects, they flip-flop the message, dismissing concerns by saying only 1 in 100 people suffers a side effect, even if that represents a 50% increase. "Many physicians don't know the NNT," says Dr. Darshak Sanghavi, a pediatric cardiologist and assistant professor of pediatrics at the University of Massachusetts Medical School and a fan of using NNTs.
The whole statin story is a classic case of good drugs pushed too far, argues Dr. Howard Brody, professor of family medicine at the University of Texas Medical Branch at Galveston. The drug business is, after all, a business. Companies are supposed to boost sales and returns to shareholders. The problem they face, though, is that many drugs are most effective in relatively small subgroups of sufferers. With statins, these are the patients who already have heart disease. But that's not a blockbuster market. So companies have every incentive to market their drugs as being essential for wider groups of people, for whom the benefits are, by definition, smaller. "What the shrewd marketing people at Pfizer and the other companies did was spin it to make everyone with high cholesterol think they really need to reduce it," says Dr. Bryan A. Liang, director of the Institute of Health Law Studies at the California Western School of Law and co-director of the San Diego Center for Patient Safety. "It was pseudo-science, never telling you the bottom-line truth, [which is] that the drugs don't help unless you have pre-existing cardiovascular disease." The marketing worked, Liang says, "even in the face of studies and people screaming and yelling, myself included, that it is not based on evidence."
Pfizer replies that the industry is "highly regulated" and that every message in ads and marketing "accurately reflects Lipitor's labeling and the data from the clinical trials."
Drugmakers, however, do make sure that the researchers and doctors who extol the benefits of medications are well compensated. "It's almost impossible to find someone who believes strongly in statins who does not get a lot of money from industry," says Dr. Rodney A. Hayward, professor of internal medicine at the University of Michigan Medical School. The NCEP's 2004 guideline update garnered headlines by recommending lower targets for bad cholesterol, which would put more Americans on the drugs. But there was also a heated controversy in the medical community over the fact that 8 of the 9 experts on the panel had financial ties to industry. "The guideline process went awry," says Michigan State's Barry. He and 34 other experts sent a petition of protest to the National Institutes of Health, saying the evidence was weak and the panel members were biased by their ties to companies.
EASY METRICS
The appearance of conflict of interest is "very important to organizations like ours, and we are all taking it seriously," responds NIH official and NCEP coordinator Dr. James I. Cleeman. "But the facts of the science were entirely correct."
Yet Cleeman's confidence is not universally shared. To statin critics, Americans have come to rely too much on easy-to-grasp health markers. People like to have a metric, such as cholesterol levels, that can be monitored and altered. "Once you tell people a number, they will be fixated on the number and try to get it better," says University of Texas' Brody. Moreover, "the American cultural norm is that doing something makes us feel better than just watching and waiting," says Barry. That applies to doctors as well. They are being pushed by the national guidelines, by patients' own requests, and by pay-for- performance rules that reward physicians for checking and reducing cholesterol. "I bought into it," Brody says. Not to do so is almost impossible, he adds. "If a physician suggested not checking a cholesterol level, many patients would stomp out of the office claiming the guy was a quack."
Yet Brody changed his mind. "I now see it as myth that everyone should have their cholesterol checked," he says. "In hindsight it was obvious. Duh! Why didn't I see it before?"
Cholesterol is just one of the risk factors for coronary disease. Dr. Ronald M. Krauss, director of atherosclerosis research at the Oakland Research Institute, explains that higher LDL levels do help set the stage for heart disease by contributing to the buildup of plaque in arteries. But something else has to happen before people get heart disease. "When you look at patients with heart disease, their cholesterol levels are not that [much] higher than those without heart disease," he says. Compare countries, for example. Spaniards have LDL levels similar to Americans', but less than half the rate of heart disease. The Swiss have even higher cholesterol levels, but their rates of heart disease are also lower. Australian aborigines have low cholesterol but high rates of heart disease.
Moreover, says MSU's Barry, cholesterol-lowering medications other than statins "do not prevent heart attacks or strokes." Take Zetia, which blocks absorption of cholesterol from the intestines. Marketed by Merck and Schering-Plough, the drug brought in $1.5 billion in 2006, with sales climbing 25% in the first half of 2007, says IMS Health (RX). The companies combined it with a statin to create a drug called Vytorin, with over $2 billion in sales in 2007.
In an eagerly awaited trial completed in 2006, the companies compared Zetia plus a statin with a statin alone in patients with genetically high cholesterol. But the drugmakers delayed announcing the results, prompting scientific outrage and the threat of a congressional investigation. The results, finally revealed on Jan. 14, showed the combination of Zetia and a statin reduced LDL levels more than the statin alone. But that didn't bring added benefits. In fact, the patients' arteries thickened more when taking the combination than with the statin alone. Skip Irvine, a spokesman for the joint venture, says the study was small and insists there's a "strong relationship between lowering LDL cholesterol and reducing cardiovascular death."
IRRELEVANT LDL?
If cholesterol lowering itself isn't a panacea, why is it that statins do work for people with existing heart disease? In his laboratory at the Vascular Medicine unit of Brigham & Women's Hospital in Cambridge, Mass., Dr. James K. Liao began pondering this question more than a decade ago. The answer, he suspected, was that statins have other biological effects.
Since then, Liao and his team have proved this theory. First, a bit of biochemistry. Statin drugs work by bollixing up the production of a substance that gets turned into cholesterol in the liver, thus reducing levels in the blood. But the same substance turns out to be a building block for other key chemicals as well. Think of a toy factory in which the same plastic is fashioned into toy cars, trucks, and trains. Reducing production of the plastic cuts not only the output of toy cars (cholesterol) but also trucks and trains. In the body, these additional products are signaling molecules that tell genes to turn on or off, causing both side effects and benefits.
Liao has charted some of these biochemical pathways. His recent work shows that one of the trucks, as it were—a molecule called Rho-kinase—is key. By reducing the amount of this enzyme, statins dial back damaging inflammation in arteries. When Liao knocks down the level of Rho-kinase in rats, they don't get heart disease. "Cholesterol lowering is not the reason for the benefit of statins," he concludes.
The work also offers a possible explanation of why that benefit is mainly seen in people with existing heart disease and not in those who only have elevated cholesterol. Being relatively healthy, their Rho-kinase levels are normal, so there is little inflammation. But when people smoke or get high blood pressure, their Rho-kinase levels rise. Statins would return those levels closer to normal, counteracting the bad stuff.
Add it all together, and "current evidence supports ignoring LDL cholesterol altogether," says the University of Michigan's Hayward. In a country where cholesterol lowering is usually seen as a matter of life and death, these are fighting words. A prominent heart disease physician and statin booster fumed at a recent meeting that "Hayward should be held accountable in a court of law for doing things to kill people," Hayward recounts. NECP's Cleeman adds that, in his view, the evidence against Hayward is overwhelming.
But while the new analyses may rile those who have built careers around the need to reduce LDL, they also point the way to using statins more effectively. Surprisingly, both sides in the debate agree on the general approach. For anyone worried about heart disease, the first step should always be a better diet and increased physical activity. Do that, and "we would cut the number of people at risk so dramatically" that far fewer drugs would be needed, says Krauss. For those people who still might benefit from treatment, a recent analysis by Hayward shows that statins might better be prescribed based on patients' risk of heart disease, not on their LDL cholesterol levels. The higher the risk, the better the drugs seem to work. "If two patients have the same risk, the evidence says they get the same benefit from statins, whatever their LDL levels," Hayward says.
Ways to fine-tune this approach may be coming soon. The company that first sequenced the human genome, Celera Group (CRA), has found a genetic variation that predicts who benefits from the drugs. Perhaps 60% of the population has it, says Dr. John Sninsky, vice-president of discovery research, and for everyone else, the NNT is sky-high. "It does not relate at all to your cholesterol level," Sninsky adds.
If the drugs were used more rationally, drugmakers would take a hit. But the nation's health and pocketbook might be better off. Could it happen? Will data on NNTs, the weak link to cholesterol, and knowledge of genetic variations change what doctors do and what patients believe? Not until the country changes the incentives in health care, says UCLA's Hoffman. "The way our health-care system runs, it is not based on data, it is based on what makes money."
The credibility of the pharma industry is at stake - well actually it is out the window with this one. It would be in the industry best interest and ours (the consumers) if the wrongdoers are sent to prison. If heads do not roll, the industry will suffer even more.Congress Investigating Vytorin Ads
WASHINGTON -
Congress is investigating advertising for the cholesterol-busting drug Vytorin following a study that suggested the pill may have no advantage over a generic cholesterol medicine, according to letters released Wednesday.
In letters dated Wednesday and addressed to Schering-Plough Corp. and Merck & Co., which jointly sell Vytorin, and the U.S. Food and Drug Administration, Reps. John Dingell and Bart Stupak, Michigan Democrats, raised questions about the ads for the medicine.
In the letter to the companies, the congressmen wrote that the House of Representatives' Committee on Energy and Commerce and its Subcommittee on Oversight and Investigations are probing the "withholding of clinical trial data that may significantly affect the medical management of hypercholesterolemia, as well as the use of misleading statement in direct-to-consumer advertisements for prescription medicines."
Vytorin is in the news this week after the results of a long-awaited study, called Enhance, indicated the drug may be no better than a generic statin at slowing the progression of heart disease.
In the FDA letter, the lawmakers write that they are "concerned that the study's results may have been available to Schering-Plough and Merck officials, and yet the massive advertisement campaign for Vytorin was allowed to continue." They ask for agency records related to the Vytorin ads.
The congressmen also asked the companies for records related to the ads as well materials related to Enhance study leader John Kastelein, a cardiologist in the Netherlands. They also seek information about the press release this Monday that disclosed the Enhance results, almost two years after the last patient completed the study.
In 2005, the companies spent $155 million on Vytorin ads, a budget exceeded that year only by Sepracor Inc.'s Lunesta campaign and AstraZeneca PLC's Nexium ads, according to an article in the New England Journal of Medicine.
The companies have defended their handling of the Enhance study.
The Zetia-Vytorin study shows that even when a drug lowers cholesterol dramatically, plaque can increase in a person's arteries. That means that the core claim of all the cholesterol drug makers is called into question by the study. The rupture of plaque is what causes most heart attacks. The closure of arteries by plaque is what causes progressive coronary artery disease.Editorial
Cholesterol Drug Bombs
There have long been suspicions, but it was still very disturbing to learn this week that a heavily promoted cholesterol-lowering drug had flunked a clinical trial of its effectiveness in reducing fatty deposits in arteries. The two companies that reap billions from the drug had been cynically sitting on the results for more than a year.
The drug, Zetia, and a combination pill that contains it, Vytorin, are made by Merck and Schering-Plough and used by millions of patients. They generated more than $5 billion in sales last year. The companies sponsored a clinical trial of the drug’s effectiveness in hopes that positive results would strengthen their marketing efforts.
The trial was conducted in 720 European patients with genes that cause abnormally high cholesterol levels. For two years, the patients received either Zocor, an older cholesterol drug, or Vytorin, a combination of Zocor and Zetia. The assumption was that Vytorin would reduce the growth of fatty plaques — a risk factor for heart attacks and strokes — more than Zocor alone. As it turned out, the plaques grew almost twice as fast in patients taking the Vytorin.
There are reasons to be cautious about interpreting these results. The number of patients was relatively small. And many of them may have used different drug treatments for years before entering the trial, possibly diminishing the effectiveness of adding Zetia.
The companies’ grudging release of the data has raised disturbing questions. A House committee will explore whether they withheld the results lest they interfere with sales and only released them under pressure from Congress and news media reports. Whatever the committee discovers, the experience is one more argument for why scientists involved in studies sponsored by drug companies must insist on the right to review and release data. A new law that strengthens the penalties for companies that do not release data promptly should help.
The findings also raise doubts about the current belief that lowering cholesterol is the key to cardiovascular health. The study showed that Vytorin reduced bad cholesterol significantly more than Zocor alone. The problem was that it failed to reduce the formation of plaque.
The companies are conducting three large clinical trials to test whether Vytorin can nevertheless reduce heart attacks and strokes. Results won’t be available until at least 2011. Meanwhile, with no evidence of effectiveness in plaque-reduction, it seems clear that Zetia and Vytorin should be used sparingly, in cases where all other cholesterol drugs have failed.
We were a bit nervous about slamming the pharma companies yesterday for covering up the results of a scientific study of their drugs. Hey. Maybe they are really good folks, just a bit slow in publishing results of the study of their cholesterol drugs Vytorin and Zetia.Dr. Steven E. Nissen, the chairman of cardiology at the Cleveland Clinic, said the results were “shocking.”And another thing from the Times:
“This is as bad a result for the drug as anybody could have feared,” said Dr. Nissen, a widely published researcher and senior consulting editor to the Journal of the American College of Cardiology. Millions of patients may be taking a drug that does not benefit them, raising their risk of heart attacks and exposing them to potential side effects, he said. Patients should not be given prescriptions for Zetia unless all other cholesterol drugs have failed, he said.
Dr. Harlan M. Krumholz, a cardiologist at Yale, said drug companies had a responsibility to release all their trial findings, positive or negative, as quickly as possible — even if the results might hurt sales.And one more point:
“People may have been on this drug without the ability to know that there was additional data that may have thrown into question its effectiveness,” Dr. Krumholz said. “That’s extremely unfortunate, and that’s an understatement.”
The Enhance trial was meant to prove that Vytorin’s combination of Zetia and Zocor would reduce the growth of fatty plaque in the arteries more than Zocor alone. Instead, the plaque actually grew almost twice as fast in patients taking the combination.Accordingly we conclude that these pharma executives are bad, bad people.
Reducing plaque growth is crucial, because plaque formation — known as atherosclerosis — can lead to the blockages and blood clots that cause heart attacks and strokes, said Dr. Howard N. Hodis, a cardiologist at the University of Southern California. That is why the trial’s finding is worrisome, Dr. Hodis said.
“Clearly, progression of atherosclerosis is the only way you get events,” Dr. Hodis said. “If you don’t treat progression, then you get events.”
The results of the trial require further investigation, Dr. Hodis said. “That just can’t be ignored.”
Cholesterol Drug Has No Benefit in Trial
By ALEX BERENSON
A clinical trial of Zetia, a cholesterol-lowering drug prescribed to about 1 million people a week, failed to show that the drug has any medical benefits, Merck and Schering-Plough said on Monday.
The results will add to the growing concern over Zetia and Vytorin, a drug that combines Zetia with another cholesterol medicine in a single pill. About 70 percent of patients who take Zetia do so in the form of Vytorin, which combines Zetia with the cholesterol drug Zocor.
While Zetia lowers cholesterol by 15 to 20 percent in most patients, no trial has ever shown that it can reduce heart attacks and strokes — or even that it reduces the growth of the fatty plaques in arteries that can cause heart problems.
This trial was designed to show that Zetia could reduce the growth of those plaques. Instead, the plaques actually grew somewhat faster in patients taking Zetia along with Zocor than in those taking Zocor alone. Patients in the trial who took the combination of Zetia and Zocor were receiving it in the form of Vytorin pills.
Dr. Steven Nissen, the chairman of cardiology at the Cleveland Clinic, said the results were “shocking.” Patients should not be prescribed Zetia unless all other cholesterol drugs have failed, he said.
“This is as bad a result for the drug as anybody could have feared,” Dr. Nissen said. Millions of patients may be taking a drug that has no benefits for them, raising their risk of heart attacks and exposing them to potential side effects, he said.
Both companies’ stocks were down in mid-day trading in New York on Monday, with Merck’s share price off by 2.4 percent and Schering-Plough’s down nearly 6 percent.
The results will also add to the controversy surrounding a long delay in releasing the results of the trial, which was known as Enhance. Merck and Schering-Plough completed the trial in April 2006 and had initially planned to release the findings no later than March 2007. But the companies then missed several self-imposed deadlines, blaming the complexity of the data analysis from the study and saying they did not know when or if the data would be ready for publication.
Last month, after several news articles highlighted the delay, they finally agreed to release the results soon.
For Merck and Schering-Plough, which jointly market Zetia and Vytorin and share profits from the drugs, the trial’s results are a serious setback. Zetia and Vytorin are important contributors to both companies’ profits, especially to Schering, which is smaller and less profitable than Merck.
Analysts estimate that about 70 percent of Schering’s earnings depend on the drugs. The controversy over the trial is also a problem for Merck, which is trying to repair its reputation after withdrawing the painkiller Vioxx from the market in September 2004.