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Red Yeast Rice Supplements: Not a Safe Alternative to Statins

Posted by medconsumers on July 1, 2009

Many people who cannot tolerate any of the cholesterol-lowering drugs called statins (e.g., Lipitor, Pravachol, Zocor) turn to an herbal supplement called red yeast rice, which lowers the low-density lipoprotein (LDL) cholesterol. Statin intolerance is most often chalked up to muscle pain (myalgia). A rare side effect of all statins is the potentially fatal disease called rhabdomyolysis, which causes destruction of the skeletal muscles.

A new trial, with only 62 statin-intolerant participants, randomly assigned them to take either red yeast rice supplements (1800 mg) or a placebo twice daily for six months. All took part in a 12-week program of education, diet, exercise, and relaxation sponsored by a local cardiology practice.

Both groups lost weight but the people taking the supplements showed greater reductions in LDL than the people on placebos. And the supplement group did not suffer more muscle pain. Yet despite these promising findings, the editorial that accompanied this study, published recently in Annals of Internal Medicine, advised doctors not to recommend the red yeast rice supplement. Reason: it is “an unapproved, unstandardized form of lovastatin labeled as a nutraceutical.”

The basis for this charge is a 2008 test of ten different brands of red yeast rice supplements by ConsumerLab.com. This independent testing group revealed that all ten supplements contained naturally occurring statin compounds in varying doses—some as high as that of prescription statins. This explains why the supplement used in the new study contained lovastatin (sold under the brand name: Mevacor).

There are other reasons why the new trial failed to show that supplements are better than statins. It lasted only six months and thus could not rule out the possibility that red yeast supplements taken longer would cause muscle pain. Unlike statins, the supplements have not been proven to reduce the risk of heart attack and stroke. The new study was primarily funded by the Commonwealth of Pennsylvania.

For information on the risks and small benefits of statin drugs, read this. And if you are taking Zetia or Vytorin, read this. And if you want to know more about statin drugs vs. the Mediterranean diet, read this.

Maryann Napoli, Center for Medical Consumers©

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Take a Closer Look at Statin’s Benefit

Posted by medconsumers on December 1, 2008

Going on Statin’s? Take a New Look at the Size of the Benefit

The current practice of advising healthy adults to go on prolonged drug therapy just got a big boost from a large international trial. It found that people with normal cholesterol can halve their risk for heart attack and stroke by taking the cholesterol-lowering statin drug Crestor (generic name: rosuvastatin). Although at low risk for heart disease, all the participants had high blood levels of C-reactive protein, or CRP, which indicates the presence of inflammation within the artery walls.

This trial, which is expected to greatly expand the market for Crestor, was funded by its maker, AstraZeneca. And it is the brainchild of the lead author Paul M. Ridker, MD, who co-owns the patent on the CRP test. The 17,802 participants—men 50 or older and women 60 or older—were randomly assigned to take either 20 mg Crestor or a placebo each day. Results were so definitively in favor of Crestor that the trial was stopped three years ahead of its five-year schedule. Millions more healthy Americans are now candidates for Crestor, and there is talk of including a CRP screening with the routine blood test for cholesterol.

The findings from this trial called JUPITER were first presented early last month at a meeting of the American Heart Association. The next day, they became freely accessible at the Web site of The New England Journal of Medicine days before the intended publication date—a move that signals the importance of new trial results.

Crestor’s 50% reduction in cardiac events was widely reported in the media, but few reporters explained that this statistic is actually far more modest than meets the eye. JUPITER’s finding is, in fact, no different from the results of other trials designed to test whether a drug can prevent a disease in healthy people—only a tiny minority will benefit from years of drug therapy.

If the small chance of benefit is important to you, so too is this critical look at JUPITER.

50% reduction explained:

JUPITER defined cardiac events as heart attack, stroke or confirmed death from cardiovascular causes. According to the editorial that accompanied JUPITER, at least one of these cardiac events occurred in 1.8% of the participants in the placebo group (157 of 8,901 participants) and 0.9% of those taking Crestor (83 of the 8901 participants). In short, over the nearly two-year duration of the trial, few of these low-risk people had a cardiac event whether they were taking Crestor or not. To single out cardiovascular deaths, there were 37 deaths in those taking placebos and 31 deaths in those on Crestor.

What it means to you:

If you fit the profile of the people who participated in JUPITER, your chance of benefiting from Crestor is also explained in the editorial that accompanied JUPITER: For every 120 people who take Crestor for nearly two years, one cardiac event will be avoided. Or, put another way: Out of every 120 people who take Crestor, 119 will receive no benefit.


Profile of the participants:

JUPITER excluded people with diabetes, high LDL cholesterol, uncontrolled hypertension, cancer diagnosed in the past five years, or inflammatory ailments, such as severe arthritis, lupus or inflammatory bowel disease—among other conditions too numerous to mention in this space.


Stopping JUPITER early:

All major trials have a Data and Safety Monitoring Board. For ethical reasons, JUPITER’s DSMB stopped the trial as a majority of participants neared the two-year mark when those on the placebo had nearly 1% more cardiac events than those on Crestor. The early stopping of trials, an increasingly common practice, has been criticized by researchers and consumer groups. It favors the drug company’s interest since more adverse effects are likely to be reported if the trial is allowed to continue. On the other hand, the benefit may also increase. Some of the JUPITER participants were tracked for nearly five years. The difference in favor of Crestor continued a steady increase as these participants neared the five-year point.


Adverse events:

There was a small increase in the diagnosis of type 2 diabetes in people taking Crestor. This increase comes close to the nearly1% benefit shown for Crestor. Newly diagnosed diabetes was reported in 3.0% of people on Crestor and 2.4% of people on placebos. The rate of any serious adverse event was the same whether participants were taking Crestor or a placebo. However, JUPITER followed participants for a median of 1.9 years, and people take statins for the rest of their lives.


Other long-term statin info:

Since 1995, nine primary prevention trials, comparing a statin drug with a placebo, have been published. They followed participants for about five years. Although all the trials collected serious adverse events, all have failed to make the complete data available to researchers. Thus, the safety of statins is unknown.

Interesting statistic:

25% of the participants in JUPITER who were assigned to take Crestor had stopped taking the drug when the trial was stopped at 1.9 years.

Noteworthy aspects of JUPITER:

This is the first trial to have a representative proportion of female, Hispanic, and African-American participants. Findings were separated out according to subgroups which showed that the reductions in cardiac events were roughly the same for all—50%.

Noteworthy previous research:

JUPITER is not the first trial to show that a statin drug can benefit people with no history of heart disease or high LDL cholesterol. Other statins—e.g., lovastatin (Mevacor), pravastatin (Pravachol)—produced similar, though slightly smaller, reductions in cardiac events. These studies, which date back to 1999, provided the first hints that the benefit of statins may be unrelated to their cholesterol-lowering effect (they are far better at lowering cholesterol than they are at lowering the risk for stroke, heart attack and death).


Cost:

Crestor is still under patent and is therefore not available generically. A month’s supply of Crestor is $105. The cost of statins, including generic versions, can vary considerably, according to Consumer Reports. A month’s supply of another statin, sold generically as simvastatin, can cost $30 at some retail pharmacies and as little as $6 at Costco.

Inflammation and heart disease:

The role of CRP and inflammation in heart disease is hotly debated, according to The New York Times, which quoted Paul M. Ridker, MD, the lead author of JUPITER, saying that he believes inflammation plays an important role, probably by causing plaque in the arteries to rupture. Dr. Ridker went on to say, “Screening for cholesterol alone is like having two passengers in a car but only one air bag. If we’re not screening for CRP, we don’t have the opportunity to save that person’s life.” Dr. Ridker, a cardiologist at Harvard Medical School, co-owns the patent on the test that measures CRP. He is expected to earn millions of dollars once it becomes part of the routine blood test for all adults.


Other conflicts of interests:

Dr. Ridker and most of his 13 JUPITER co-authors have received grants, lecture and consulting fees, and other funding from AstraZeneca and other drug companies, many of which make statin drugs. The list at the end of the JUPITER paper in The New England Journal of Medicine was so extensive that it took up six inches of tiny type.


Should you be tested?

Some say JUPITER calls into question the prevailing hypothesis that high cholesterol is a major risk factor for heart disease. This position is bolstered by the long-known, but oft-forgotten, fact that half of all heart attacks occur in people with normal cholesterol levels. Many assume that CRP testing will soon become routine.

In one of their excellent podcasts recorded at the University of British Columbia, Vancouver, (www.ti.ubc.ca), James McCormack, Pharm.D, and Michael Allan, MD, dismissed the obsession among some researchers who are trying to tease out whether statins work by lowering cholesterol, or reducing inflammation or some other mechanism. McCormack and Allan say that statins clearly reduce the risk for cardiac events, and this was shown to be 1% in low-risk people like the JUPITER participants. Other trials show the benefit is higher in high-risk people, e.g., the 2% benefit for those who have had a heart attack or stroke. If these benefit rates sound good to you, say McCormack and Allan, then just take the statin and forget about having your CRP or cholesterol measured—they add nothing to the decision.


For more information:

To read the JUPITER trial findings, click here. Physicians from all over the world have answered the journal’s survey, asking whether JUPITER will change their practice. Their comments can also be read at the Web site.

Maryann Napoli, Center for Medical Consumers ©

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Why is Anyone Taking Zetia or Vytorin?

Posted by medconsumers on October 1, 2008

Vytorin and Zetia Continue to be Prescribed Despite Hints of Harms and No Proof of Benefit

There is no proof that Zetia can do anything beyond lowering cholesterol—no evidence that it can reduce heart attacks or cardiovascular disease, which, of course, is the ultimate goal. Once again, this blockbuster drug sold alone or as a combination medicine has produced negative clinical trial results. This time it failed to provide any benefit to people with heart-valve disease. Worse, there were more cancers and cancer deaths among the drug-treated participants than in those taking a placebo, though these findings are described as “due to chance.”

Release of preliminary results of this trial had generated so much interest in the media last summer that The New England Journal of Medicine allowed the final results to be available on its Web site in early September—well in advance of the planned publication date.

Zetia is a relatively new cholesterol-lowering drug that can be prescribed alone. Vytorin combines Zetia with the 22-year-old statin drug, called simvastatin (brand name Zocor), into a single pill. Last year this expensive, heavily promoted combination drug became what only can be described as a drug maker’s worst nightmare. Study results showed that Vytorin was no better at reducing atherosclerosis of the carotid (neck) arteries than the older, cheaper simvastatin alone. There was also a hint that Vytorin might actually worsen artery disease.

And if that’s not bad enough, Merck and Schering-Plough Corp., which jointly market Vytorin, had withheld these unfavorable study results for nearly two years. It was, of course, in the financial interest of both companies to do so because Vytorin and Zetia are among the top-selling drugs worldwide. Four years after both drugs went on the market, backed by an aggressive ad campaign that featured a “food and family” cholesterol theme, yearly sales reached $5.2 billion.

On its Web site last month, The New England Journal of Medicine also published an editorial and an analysis that addressed Vytorin’s possible cancer-causing effect. The analysis was based on all the people diagnosed during the new heart-valve study and two other, much larger ongoing Vytorin trials. It was conducted by an Oxford University, U.K, research team, which found no increase in cancer incidence, but did find an increase in cancer deaths among those taking Vytorin. This finding was described as due “entirely to the play of chance rather than to a true increase in cancer mortality.”

The New England Journal of Medicine editors, however, are not so sure. In an editorial, they described a plausible mechanism for a cancer-causing effect, “[Zetia] interferes with the gastrointestinal absorption not only of cholesterol, but also other molecular entities that could conceivably affect the growth of cancer cells.” Once the cancer concerns were made public again last month, the FDA announced that its own analysis is in the works.

What makes this Vytorin/Zetia story so appalling is the fact that Zetia’s only advantage over the older statin drugs is a 17% greater reduction in LDL cholesterol. Incredibly, Merck and Schering-Plough were able to sell doctors and the public on the idea that this is more important than proof that this drug can cut the risk of heart attack (which has been proven for statins prescribed to high-risk men and people with heart disease). Zetia was studied for only 12 weeks before it went on the market.

Despite their uncertain safety records, Zetia and Vytorin continue to be prescribed to people with high LDL cholesterol. After the initial bad publicity, sales of Vytorin and Zetia dropped 40% in the first six months of 2008. That’s encouraging. But the question remains: Why is anyone still taking these drugs?

Maryann Napoli, Center for Medical Consumers ©
October 2008

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Failed Vytorin Study Raises Questions About Cholesterol

Posted by medconsumers on February 1, 2008

A firestorm of bad publicity erupted over cholesterol drugs last month when an expensive combination drug proved to be no better than an older drug alone. This finding was suppressed for 20 months by Merck and Schering-Plough, the two companies that make Vytorin, which is a one-pill combination of Zetia and Zocor. Their two-year trial failed to prove that Vytorin is better than Zocor alone for slowing plaque accumulation; instead atherosclerosis worsened in those taking Vytorin.

But the study results were not revealed until the two drug companies were pressured into doing so by an article in The New York Times and a Congressional inquiry. Worldwide, about one million prescriptions for Vytorin and Zetia are written each week, and they generated about $5 billion in sales last year. Zocor can be purchased under its generic name simvastatin for less than $6 for a month’s supply; whereas an equivalent amount of Vytorin costs about $100. It was obviously in the two companies’ interest to withhold the negative results for as long as they could get away with it.

When Vytorin came on the market two years ago, it was impossible not to be cynical about its purpose. Merck’s patent for Zocor was running out, and its blockbuster status would soon be diminished with generic competition. The company joined forces with Schering-Plough, maker of Zetia, and sought FDA approval for Vytorin. Their FDA-required trials showed a 17% greater reduction in LDL, the so-called bad cholesterol, than Zocor alone.

Making this 17% reduction in LDL look like an amazing achievement was not much of a stretch. Merck and the makers of other statin drugs like Lipitor and Pravachol had already paved with way. Their respective marketing machines had long ago misled most of us (doctors included) into thinking that cholesterol reductions equal heart attack reductions. One consistently overlooked fact about statins: They are far better at lowering cholesterol than preventing heart attacks or strokes. And those small reductions in heart attacks and strokes shown in clinical trials are largely confined to high-risk middle-aged men and those with heart disease or diabetes. Vytorin, on the other hand, has not been proven to reduce heart attacks or strokes in anyone.

LDL Reduction Irrelevant

Though doctors tend to focus their statin-taking patients on the size of their LDL reductions, heart disease researchers have long ago noted that this is likely irrelevant. Statin trials often show that the size of the cholesterol reductions are not consistent with reductions in heart attacks. Such observations led researchers to suspect that the ability of statins to reduce heart attacks and strokes has less to do with cholesterol reduction and more to do with other biological effects like plaque stability and anti-inflammatory effects. Another important but overlooked observation: “Elevated LDL identify less than one half of individuals who will die from coronary heart disease” (Rosenson et al. Antithrombotic Properties of Statins, JAMA, May 27, 1998).

The fall-out from the Vytorin debacle continues to reverberate. At this writing, Merck and Schering-Plough are running full-page ads daily in the Times and Wall Street Journal, warning people not to be confused by a single study and to continue taking Vytorin. The advice was backed by the American Heart Association, which appeared to be an independent source until The Times reported that the AHA receives nearly $2 million a year from Merck/Schering-Plough Pharmaceuticals.

One of the unintended consequences of two drug companies withholding their negative trial results is that it led some in the media, notably Alex Berenson, an investigative reporter for the Times, to look back at another important failed cholesterol drug trial and question the very foundation of heart disease prevention. In his heretically titled article “Cholesterol as a Danger Has Skeptics,” Berenson cites Pfizer’s trial of its much-anticipated drug torcetrapib that raised HDL, the good cholesterol, and lowered LDL. The trial had to be stopped in 2006 because the drug caused heart attacks and strokes. (Sound familiar? Postmenopausal hormones were widely prescribed because they were so good at improving cholesterol levels but they also increased the risk of heart attack, stroke and blood clots.) “Torcetrapib’s failure shows that lowering cholesterol does not prove a drug will benefit patients,” said a skeptical Walter Reed cardiologist quoted in Berenson’s article.

Many researchers, physicians and scientists around the world have long questioned the import of high cholesterol for anyone other than middle-aged men. In fact there is an International Network of Cholesterol Skeptics (disclosure: we belong), but the skeptics have been marginalized over the years. Now some mainstream media like Business Week and the cardiology Web site, TheHeart.org are willing to give them voice.

Could the house of cards be falling? Would the house of cards be allowed to fall when a worldwide $40 billion-a-year industry is at stake?

For More Information

The International Network of Cholesterol Skeptics www.thincs.org

Business Week magazine (www.businessweek.com) click into past issues, January 17, 2008 Lipitor cover story: “Do Cholesterol Drugs do any Good?”

TheHeart.org from Web MD www.theheart.org, see video blog of Eric J. Topol, MD, who questions the import of LDL reduction in “Temple of the LDL Cholesterol.”

Maryann Napoli, Center for Medical Consumers ©
February 2008

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Heart News 2007

Posted by medconsumers on December 31, 2007

The heart-related news has lately been a roller coaster of good, bad, and maybe not so bad. One popular prescription cholesterol-lowering statin drug might soon be sold over the counter. Defibrillators of the kind implanted years ago in Vice President Dick Cheney were in the news last month when studies showed they are more likely to be given to white men. But this needn’t be seen as yet-another example of women and minorities deprived of appropriate heart care. A new study showed that men with implanted defibrillators had a higher death rate than women with exactly the same heart condition who were not given implanted defibrillators.

And remember those drug-coated stents that scared heart patients over a year ago when it was announced that they increased the risk of potentially fatal blood clots long after they were inserted to prop open a constricted artery? Well, drug-coated stents made headlines again last month suggesting that they may not be so dangerous after all.

What do we make of all this?

For starters, an over-the-counter cholesterol-lowering drug might be a good idea for certain people. Not simply as a money-saver, but as a means of getting good-quality written drug information to the user. With a few exceptions, prescription drugs do not automatically come with FDA-approved printed information, though it comes tucked into the packaging of virtually all drugs sold over the counter.

We might be grasping at straws here, but mandated consumer drug information produced with FDA oversight is far better than the current situation. Then warnings like this about Lipitor—“tell your doctor if you have more than two drinks a day”—might actually reach the people who take the drug.

The prescription drug under consideration for over-the-counter status is Mevacor. That it is a statin drug and therefore a member of the top-selling drug class worldwide—$35 billion in annual sales—makes the switch all the more interesting. (Other statins are Lipitor, Crestor, Lescol, Pravachol, and Zocor.) Merck, the company that makes Mevacor, has recently applied to the FDA for permission to sell the drug over the counter. And an advisory committee of experts will decide the issue this month. (In 2005, an FDA Advisory Committee rejected a similar application for Mevacor.)

Two statin drugs Pravachol and Zocor are already available generically, which means that their patents have run out and now any company can produce these drugs under their generic names at a far lower cost than any brand-name statin. For example, Zocor, prescribed generically as simvastatin, costs from 75 cents to $1 a day at most retail drug stores and 10 cents a day, if purchased at a discount pharmacy like Costco’s. Lipitor, on the other hand, can cost $2.50 to $4 a day. From the FDA point of view, generic versions are equivalent to branded drugs because they must go through a process of proving that to the agency.

Many drug plans are encouraging members who take an expensive statin to switch to one of the generic versions with financial incentives like lower co-payments. And if Mevacor gets FDA approval for over-the-counter sale, statin users will have yet another low-cost alternative with the added feature of eliminating some doctor visit charges.

All this is cutting into the huge profits long enjoyed by Pfizer, the company that makes Lipitor, which is the most prescribed drug in the world. Naturally, the company wants to make as much money as possible before Lipitor loses its patent in March 2010. Consequently, Pfizer has escalated its long-running ad campaign featuring Dr. Robert Jarvik, inventor of the Jarvik artificial heart, who has been hugely successful in convincing many doctors and consumers that Lipitor is superior to other statins.

Currently, some of the Jarvik/Lipitor ads, say, “There’s a common misconception that all cholesterol-lowering medications are the same.” And more specifically, “In clinical studies LIPITOR lowered bad cholesterol significantly more than generic Zocor and Pravachol.”

Both points refer to a 2004 clinical trial that found people with heart disease showed a reduced degree of atherosclerosis progression if they were on high-dose Lipitor (80 mg) for 18 months, compared with those on a moderate dose of Pravachol (40 mg). There was also a greater reduction in LDL, or “bad” cholesterol, shown in the heart patients who took the high-dose Lipitor.

Three things to keep in mind about this trial, known by its acronym REVERSAL: Its participants all had heart disease (the overwhelming majority of U.S. statin-takers do not); REVERSAL was not designed to see whether Lipitor or Pravachol prevented heart attacks or strokes. And lastly, it compared a high-dose of Lipitor with a moderate-dose of Pravachol, leaving open the possibility that Pravachol at 80 mg might be just as good. Still, REVERSAL provides the basis for the Pfizer claim that Lipitor is not only better than other statins but it should also be prescribed in high doses for people with heart disease.

As for the most crucial goals of statin therapy: all statins, with the exception of Crestor, have been shown in clinical trials that predate REVERSAL to reduce the risk of heart attack and stroke in people who already have heart disease.

Healthy But High Risk

As for people without heart disease, the proven benefit of statins is largely confined to high-risk men between 30 and 69 years. The magnitude of this benefit, however, is not impressive—1.5% fewer of those taking a statin will suffer a non-fatal heart attack. But one analysis of all statin primary prevention trials showed that this 1.5% benefit was canceled out by an equivalent risk of experiencing a serious reaction to the statin.

The promotional activities of statin manufacturers have successfully focused most doctors and the general public on the excellent cholesterol-lowering effects of these drugs. But no head-to-head comparison study of all six statins has answered the most important-to-consumers questions: Which drug is best at preventing a heart attack or stroke? How large is the benefit?

There is a Jarvik/Lipitor print ad that answers the how-large-is-the-benefit question for high-risk people without heart disease. “In patients with multiple risk factors for heart disease, Lipitor reduces risk of heart attack by 36%* if you have risk factors such as family history, high blood pressure, age, low HDL (‘good’ cholesterol) or smoking.” In smaller print, the same ad has this explanation of “reduces risk” under the asterisk: “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.” This ad is a rarity because it explains the 36% reduced risk. Take Lipitor for years and your risk of having a heart attack drops from 3% to 2%.

Lately, Pfizer has been trying to stem the exodus to generic statins by touting a new study that purportedly shows more heart attacks or strokes in people who switched from Lipitor to simvastatin, compared with those who stayed on Lipitor. There’s little reason to take this study too seriously.

First of all, Pfizer funded the study, and drug company-funded studies are notorious for coming up with conclusions that favor their products. Second, it was presented on a poster at a recent European cardiology conference, and has yet to be published or fully peer reviewed. (The New York Times, however, recently reported that this study has been accepted by the British Journal of Cardiology and will soon be published.) Lastly, the study is based on an analysis of medical records of British heart patients who did or did not switch from Lipitor to the generic version of Zocor (simvastatin). The study’s design is not regarded as high quality; in fact the authors describe its limitations this way: “This is an observational database study, and as such has recognizable limitations; therefore the findings should be regarded as hypothesis-generating.”

NB: There’s a consensus among cardiologists that statins are generally safe and are extensively studied. Perhaps they are, but three of the five major primary prevention randomized trials have not released all of their statistics on serious adverse reactions, according to James Wright, MD, and John Abramson, MD, who co-authored a commentary early this year in The Lancet, entitled “Are Lipid-Lowering Guidelines Evidence-Based?” The full story about the safety of statin drugs is unknown.

NEWS ABOUT DEFIBRILLATORS

An unexpected finding showed up when a team of Duke University researchers tracked elderly people with heart failure who did and did not have defibrillators implanted to prevent sudden death. Those who had a defibrillator implanted lived no longer than those who did not. That was the contrary-to-expectations finding 180 days after implantation.

But when these heart patients were followed longer, the results were worse for the men. Their mortality rate in the year after implantation was higher than that of women without defibrillators, though all had similar heart problems. To take into account the fact that women live longer than men, Leslie H. Curtis, PhD, and colleagues at Duke University School of Medicine, confined their study to men and women under the age of 75 years.

Their new findings come at a time when implantable defibrillators are, once again, in the news for having serious defects that have caused a few deaths. These devices monitor the patient’s heart rhythm and deliver an electric shock once dangerously erratic rhythms are detected.

The Duke researchers analyzed a national 5% sample of the Medicare claims filed for more than 35,000 people from 1991 through 2005. All had been diagnosed with heart attack and either heart failure or cardiomyopathy. Men were three times more likely than women to have the device implanted. Of those with heart disease but no prior cardiac arrest or tachycardia (rapid heartbeat), defibrillators were implanted in 32 per 1,000 men and about 9 per 1,000 women.

The gap between man and women didn’t close for the most seriously ill patients—those with prior cardiac arrest or tachycardia. For this group, the implanted defibrillator rate was 102 per 1,000 men and 38 per 1,000 women.

A related study, published in the same October 3 issue of the Journal of the American Medical Association, found that black men and women were also less likely to have a defibrillator implanted than white men.

“The bad news may not be for women and minorities, but for white men who are undergoing a procedure that for primary prevention does not extend their lives,” wrote Rita F. Redberg, MD, in an editorial that accompanied the two studies.

NEWS ABOUT DRUG-COATED STENTS

The bad news about this topic originally came from the World Congress of Cardiology in September 2006. Presented at this international conference were clinical trials that found a slightly increased risk of death and a higher rate of potentially fatal blood clots in people who had drug-coated stents implanted during a coronary-artery-opening procedure called angioplasty. The trials compared them with other heart patients whose constricted coronary arteries were propped open with stents not coated with a drug.

The higher risks among those given drug-coated stents did not show up until four years of follow-up. These complications were confirmed in two separate analyses of the combined results of company-sponsored trials by Boston Scientific, maker of the Taxus stent, or Johnson & Johnson, maker of the Cypher stent. The medicine coating these stents is intended to keep the constricted arteries from closing up again.

Last month the national media reported good news about drug-coated stents from the annual meeting of the American Heart Association in Orlando, Florida. Two-year follow-up results from a new, yet-to-be-published clinical trial showed that drug-coated stents are no more risky than bare-metal stents. Some media reports left the impression that the issue of stent safety had been resolved with this trial. “Heart Stent Gets a Reprieve From Doctors” was the over-the-top New York Times headline.

Keep in mind that the new trial announced at the heart meeting lasted only two years and the blood clots in the above-mentioned company-sponsored trials did not show up until four years. More details will be available when the new trial is published in Circulation, the journal of the American Heart Association, according to a “Late-Breaking News Release” from the heart meeting.

The meeting organizers managed to focus the media on stents rather than the more critical issue—overuse of artery-opening procedures. Many of the one million or so Americans who undergo angioplasty each year (with or without stents) can be treated just as successfully with drug therapy. It is generally the same multiple drug therapy advised for everyone who undergoes angioplasty. This was proven in a government-sponsored study called the Occluded Artery Trial, or OAT, published last year in The New England Journal of Medicine. A follow-up analysis of the OAT results was presented at the American Heart Association meeting. Yet no mainstream media reported the new OAT analysis, according to Health News Review, a medical media watchdog group led by journalist Gary Schwitzer.

All 2,166 OAT participants had a totally blocked major coronary artery and were 3 to 38 days away from suffering a heart attack. All were randomly assigned to receive an artery-opening procedure plus drug therapy or drug therapy alone. The multiple-drug therapy included daily aspirin, beta-blockers, ACE inhibitors and cholesterol-lowering drugs.

After four years, the OAT participants in the angioplasty/drugs group had the same rate of survival, second heart attack, and heart failure as the group given drug therapy alone. When the 469 American OAT participants were singled out (this was an international trial), the angioplasty-treated heart patients generated costs that were $10,000 higher than the drug-treated people. After three years, the cost difference had dropped to $7,000.

In an editorial that accompanied the OAT findings last year in The New England Journal of Medicine, L. David Hillis, MD, and Richard A. Lange, MD, wrote, “The open-artery hypothesis, although not previously validated in a prospective, randomized study, has nonetheless been embraced by many practicing physicians.” Translation: Heart surgeons have been opening constricted coronary arteries for years on the unproven premise that this will save lives and reduce the risk of a future heart attack. The OAT results failed to validate that hypothesis.

Opening a blocked artery during or right after a heart attack has been proven beneficial, but the OAT results showed no benefit to the common practice of performing angioplasty well after the patient had been stabilized—3 to 38 days after suffering a heart attack.

Maryann Napoli, Center for Medical Consumers ©
2007

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Honesty in Drug Advertising: Some rare examples

Posted by medconsumers on May 1, 2007

“In patients with multiple risk factors for heart disease, LIPITOR REDUCES RISK OF HEART ATTACK BY 36%* If you have risk factors such as family history, high blood pressure, age, low HDL (‘good’ cholesterol) or smoking.”

The noteworthy part of this New York Times ad is the asterisk and this explanation of the 36% statistic: “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.”

Take a moment to appreciate the significance of this rare finding of candor in one of those ubiquitous Lipitor ads featuring Dr. Robert Jarvik, “inventor of the Jarvik Artificial Heart and Lipitor user.” Most drug ads would rather proclaim a “36% reduction” and leave it at that, but this version shows exactly what it means. Take Lipitor for years and your risk of having a heart attack drops 1%. Granted, the explanation is in much smaller type than the 36%, but at least it’s there.

Another Jarvik/Lipitor Times ad proclaims: “In patients with type 2 diabetes, LIPITOR REDUCES RISK OF STROKE BY 48%* If you also have at least one other risk factor for heart disease…” The explanation: “That means in a large clinical study, 2.8% of patients taking a sugar pill or placebo had a stroke compared to 1.5% of patients taking Lipitor.”

It’s rare to see ads with drug benefits expressed in what statisticians call absolute risk terms, which are more understandable to the public as well as doctors. Tom Abrams, director of the FDA Division of Drug Marketing, Advertising and Communications, explained in a telephone interview that the FDA encourages drug companies that provide quantitative information (e.g., 36% reduced risk of heart attack) in their ads to show what it means. In other words, the ad must answer the question: 36% of what?

Whether quantitative information goes into an ad is up to the drug companies, but once it does, the FDA wants them to put in the explanation, Abrams said, though only the most egregious non-compliers get a warning letter. Why no explanation of the quantitative information in all TV versions of these ads? “This is a quicker media and companies believe that people can’t process the information?” he said.

Well, honesty in some print ads is better than nothing. The next thing to look for is the quantification of the drug’s severe adverse effects…in absolute risk terms.

Maryann Napoli, Center for Medical Consumers ©
May 2007

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Statins and Mediterranean Diet

Posted by medconsumers on February 1, 2007

One might reasonably expect the U.S. government’s cholesterol-treatment guidelines to be firmly based on scientific evidence. Certainly, that was the claim of the National Cholesterol Education Program when it issued an updated report in 2004. What alarmed some researchers and consumer advocates at the time was the expansion of statin use to include people who do not have heart disease but are supposedly at “moderately elevated risk” for developing it.

The updated guidelines would put an additional 23 million Americans on statins for the rest of their lives. A cloud of doubt hung over the entire issue once it became known that the majority of physicians who established the guidelines had financial ties to companies that make statin drugs.

Statins, the top-selling class of drugs in history, are cholesterol-lowering drugs that include atorvastatin (Lipitor), lovastatin (Mevacor), pravastatin (Pravachol), fluvastatin (Lescol), simvastatin (Zocor) and rosuvastatin (Crestor). Their benefit to people with heart disease is proven, but there is a controversy regarding the use of these drugs by everyone else. Three-quarters of all Americans now on long-term statin therapy do not have heart disease.

In a recent issue of the medical journal, Lancet, John Abramson, MD, Harvard Medical School, and James Wright, MD, University of British Columbia, Vancouver, co-authored a commentary entitled, “Are Lipid-Lowering Guidelines Evidence-Based?” They conducted an analysis of all the major trials in which participants were randomly assigned to take either a statin or a placebo. The seven trials that included adults between 30 and 80 years old who already have heart disease clearly showed that statins lower the risk of a cardiac death as well as a death from any cause.

However, their analysis of the other trials that included healthy but high-risk people without heart disease showed that statins should not be prescribed to women of any age who do not have heart disease or diabetes, or to men older than 69 years who do not have heart disease or diabetes because no benefit was shown for them.

There is a modest benefit for men aged 30-69 years who are at high risk of developing heart disease. Out of 50 high-risk men taking a statin every day for five years, only one avoids a “cardiac event” —that is, a heart attack or heart-related death. Put another way, out of every 50 men who stay on statins for five years, 49 risk an adverse drug reaction for no benefit. “In our experience,” wrote Drs. Abramson and Wright, “many men presented with this evidence do not choose to take a statin, especially when informed of the potential benefits of lifestyle modification on cardiovascular risk and overall benefit health.”

*****

What follows is an interview with the lead author of this analysis, John Abramson, MD, who is also the author of the 2004 book entitled, “Overdosed America” and serves as an expert consultant to plaintiffs’ attorneys in litigation involving the drug industry including Pfizer and Lipitor. He is interviewed by Maryann Napoli.

MN: Whenever I write about statins, I get calls from readers that indicate many are misled about their level of risk. Typical is the healthy woman over the age of 65 pressured to take statins by her doctor who says that she is at high risk for a heart attack solely because of age and high cholesterol.

JA: 1) The evidence shows that the higher her cholesterol, the longer she will live; 2) no trial shows that statin therapy will benefit her; 3) people over 65 who exercise routinely, eat a Mediterranean-style diet, don’t smoke, drink moderately, will have a 60% lower rate of death than the people who don’t do these things.

MN: That one trial with people over 70, called PROSPER (PROspective Study of Pravastatin in Elderly at Risk), is often misrepresented.

JA: This trial clearly showed the limited benefit of statins in the elderly. For those who already have cardiovascular disease, taking a statin reduces the risk of heart attack or cardiac death. But it also showed that people in this age range who are at increased risk of, but do not have, cardiovascular disease do not benefit from taking a statin. Importantly, the study also found that at four years, there was one extra new cancer for every 70 people taking a statin. No reduced risk of stroke and no benefit for people without cardiovascular disease and an increased risk of cancer, yet millions of elderly Americans without heart disease or diabetes are taking these drugs because they and their doctors are misled into believing that clinical trials have shown that statins are beneficial.

MN: And people who have had a heart attack?

JA: Statins are definitely helpful for people who have already had a heart attack. Still, the Lyon Diet Heart Study shows how much more effective a healthy diet is in reducing the risk of heart attack for these folks. The participants were randomly assigned to receive counseling about a Mediterranean-style diet (see end of article) or a standard post-heart attack diet. Those who went on the Mediterranean-style diet developed 72% less heart disease than those in the control group. There was also a 56% lower death rate and 61% less cancer than the people in the control group. Simply eating a Mediterranean-style diet is nearly three times more effective at preventing recurrent heart disease and death in post-heart attack patients than is taking a statin. Even more surprising, those on the Mediterranean-style diet did not have lower cholesterol than those eating the standard post-heart attack diet. So when your doctor tells you to get your cholesterol down…keep that in mind.

MN: Lifestyle changes aren’t given much attention.

JA: The vast majority of communication about heart disease is influenced by the drug companies. They focus on cholesterol, rather than diet, exercise, and not smoking because their primary responsibility is to maximize the financial return to their investors, and that’s where the money is. All but one of the major statin trials was funded by a company that makes statins.

MN: That should make us all wary—studies show that the majority of drug company-funded studies produce results favorable to their product.

JA: The ALLHAT [Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial] was the only one of the 14 major statin trials included in the most recent review [published in the Lancet in October 2005] not funded by a drug company. It included a good mix of people: men and women with and without heart disease and/or diabetes. Half of the participants were randomly assigned to be treated with a statin and half to go to their regular doctor and do whatever he or she thought was right. By the end of the study, 26% of the people assigned to “usual care” had been put on a statin by their doctors and 77% of those in the statin group were still taking the statin (the others discontinued because of side effects, other medical conditions, etc.). But the results showed that there was no less heart disease or death in the group with three times as many people taking statins.

MN: These results seem to be widely misperceived.

JA: One of the reasons is a misleading editorial that accompanied the publication of ALLHAT in the Journal of the American Medical Association. It stated: “Physicians might be tempted to conclude that this large study demonstrates that statins do not work; however, it is well known that they do.” That’s not quite what I think of as evidence-based medicine. The editorialist actually had the chutzpah to suggest that statins may be less effective when they are prescribed by primary care physicians, as they were in the ALLHAT, than by cardiologists. At the time of the editorial, the writer had financial relationships with at least seven drug companies. He is now employed by Merck, which makes Zocor.

MN: All but two of the statin trials failed to report their serious adverse events, defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization, requires prolongation of hospitalization, or results in significant disability.

JA: The statin trials that report only the drug’s effects on heart disease are not presenting what we all really need to know. The most important question is: What is the overall effect of taking the drug? In other words, if a statin decreases the risk of heart disease but does not reduce the overall risk of serious illness or death unrelated to heart disease, is it worth taking? And the difficulty of answering this question ought to lead people to wonder if there are alternative ways to reduce the risk of heart disease.

MN: Why do journals allow drug companies to publish only heart-related results of their trials?

JA: Medical journals are not fulfilling their responsibilities when they publish trial results and omit all serious adverse events and deaths from all causes.

MN: Any parting thoughts?

JA: People ask, “Why can’t I just take a pill, eat what I want and forget about going to the gym?” And I say to them: If the pill worked, that would be a good question, but there just isn’t any evidence from clinical trials showing that statins are beneficial for women or older men who don’t already have heart disease or diabetes. Healthy lifestyle changes are a more effective, less expensive, and safer way to reduce your risk of heart disease and improve your chances of staying healthy overall.

For information on the Mediterranean-style diet: go to www.americanheart.org and type into the search box: Lyon Diet Heart Study.

Maryann Napoli, Center for Medical Consumers ©

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Report Side-Effects of Statin Drugs

Posted by medconsumers on November 1, 2006

This is an excellent Web site for anyone who is currently on a statin drug or who has stopped taking one because of a serious adverse reaction. Although cholesterol-lowering statin drugs first went on the market 20 years ago, there are major information gaps concerning their adverse effects.

Beatrice A. Golomb, MD, PhD, who heads the UCSD Statin Study at the University of California at San Diego, has been working for years to change things by collecting information directly from the public. She has recently launched a new online survey (www.statineffects.com) “for people who have had adverse responses to statins or to other cholesterol-lowering drugs, and also [for] people who have done well on these drugs.” Statins are a class of cholesterol-lowering drugs that includes atorvastatin (Lipitor), simvastatin (Zocor), pravastatin (Pravachol) fluvastatin (Lescol), lovastatin (Mevacor), and rosuvastatin (Crestor).

The very existence of this study is tacit acknowledgment of deficiencies both in the FDA drug approval process and in its post-market surveillance system. Drug trials are designed to prove a benefit and typically do not provide a full picture of harm. Add to the mix the fact that most statin drugs are taken by older people. Many report to Dr. Golomb that their doctors attribute such problems as joint pain and memory deficits to aging and do not consider the possibility of statin side effects.

The site is more than a survey opportunity. It has information on known adverse effects divided into two sections: “Side Effects Your Doctor Will be Familiar With (muscle symptoms and changes in liver function, as noted in a blood test)” and “Lesser Known Side Effects” (e.g., peripheral neuropathy, memory loss, thinking and concentration problems), as well as a description of symptoms that should be reported immediately to your doctor.

Maryann Napoli, Center for Medical Consumers ©

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Statins: Low Odds of Benefit

Posted by medconsumers on July 1, 2006

Statin-Treatment Guidelines: 198 to 1 odds that the drug won’t help

Would you go on long-term statin drug therapy if you knew that the odds are one in 23,000 that the drug will save you from a cardiac death? How about one in 198? And are you prepared to stay on that drug for the rest of your life, though the full story on the drug’s harms is yet to be known? That is what the experts who put together the U.S. and Canadian statin-treatment guidelines expect of the public, according to an analysis published last month in the British Medical Journal.

So much of medical decision-making boils down to probabilities. What is my chance of having a heart attack? And how will this drug reduce the risk? Cholesterol drug ads, for example, proclaim a 25% reduction in heart attack. But that means nothing unless you know your personal odds of a heart attack. Always ask: 25% of what?

If, for example, you are a healthy middle-aged woman with high cholesterol but a tiny chance of having a heart attack in the next five years, then the drug offers a 25% reduction in those already miniscule odds. But, if you are a middle-aged male smoker who has already had a heart attack, then the 25% reduction offers a large benefit.

Researchers who study drug trials have another way of determining odds called number needed to treat. They frame the research question this way: How many people must take this drug every day for five years to save one person from a cardiac death? That formula is the basis of the new analysis of international guidelines for prescribing the cholesterol-lowering statin drugs that include Lipitor, Mevacor, Zocor, Pravachol, Crestor, and Lescol. It highlights some major deficiencies in the information intended to guide physician prescribing practices. And in turn, deficiencies in the information consumers need to make informed decisions.

The statin-treatment guidelines from five countries—Australia, Canada, New Zealand, the U.K., the U.S.—and several European medical societies were assessed by a team of Canadian researchers led by Douglas G. Manuel, MD, of the Institute for Clinical Evaluative Sciences in Toronto. The number needed to treat was determined by applying each set of guidelines to the same population of 6,760 Canadian men and women, aged 20 to 74 years.

The “winners” are the Australian and British guidelines because they are the most effective in potentially avoiding the most deaths. However, the New Zealand guidelines were deemed the most efficient because they potentially avoided almost as many deaths while recommending statin drugs to the fewest people. Based on the New Zealand guidelines, the number needed to treat is 108, or for every cardiac death prevented, 108 people must take statins for five years. (By comparison, the number needed to treat is 198 and 154, for the U.S. and Canada, respectively.)

What is most troubling about the results of this new analysis is not just that the U.S. and Canadian guidelines identify a larger pool of people as candidates for statin therapy in order to prevent one cardiac death. But it is also the fact that the crucial topic of drug-related harm was ignored by those who established the guidelines. “Treatment guidelines don’t discuss harms. I don’t know why,” said Douglas G. Manuel, MD, the lead author of the analysis, in a telephone interview.

“Harms are idiosyncratic, meaning everyone has more or less the same chance of harm. I say that with lots of caveats,” explained Dr. Manuel, a scientist and primary care physician. “But this is not so where it concerns benefits. If a person is at high risk because he has had a heart attack, then the benefit [of statin therapy] will be large. But as a person’s risk of heart disease gets lower, then I am more uncomfortable [about prescribing statins].”

The harm question was put to David Atkins, MD, medical officer at the U.S. Agency for Healthcare Research and Quality, the lead federal agency charged with improving the quality, safety, efficiency, and effectiveness of health care for all Americans. “Many guidelines about drugs skirt around the issue of harms,” he said in a telephone interview. “With anti-hypertension drugs, for example, side effects include sexual dysfunction and dry mouth, but they affect a small number of people—2-5%.” They are not addressed, Dr. Atkins explained, because it “complicates the message too much.” What’s more, he said, “Doctors tend to regard the issue of side effects as trivial in light of a heart attack.”

All of the statin-treatment guidelines are purportedly evidence based, meaning they are drawn from the same published results from clinical trials in which participants have been randomly assigned to take a statin or a placebo and followed for about five years. However, a healthy skepticism is in order where it concerns women without heart disease. A 2003 government report, Diagnosis and Treatment of Coronary Heart Disease in Women: Systematic Reviews of Evidence on Selected Topics, concluded, “There is insufficient evidence to determine whether lipid lowering [i.e., with drugs, diet or other lifestyle changes] reduces risk for any clinical outcome [e.g., heart attack, stroke].” The main reasons for the “insufficient evidence” are: women are underrepresented in statin trials and most of the trials pool the results of men and women together.

Informed decision-making about statin therapy is hampered further by another problem with medicine’s gold standard evidence—the randomized clinical trial, according to Dr. Manuel. “My expectation to get good information about harms from a randomized clinical trial is somewhat low because we are missing key parts of the information about adverse events from drugs in general, not just statins. What we need is better postmarketing surveillance,” he said, referring to mandatory reporting of adverse drug reactions after a new drug goes on the market. (Currently, reporting is voluntary and captures less than 10% of all serious adverse drug reactions.)

The FDA-required clinical trials conducted prior to approval usually have a few thousand participants at best. Only when hundreds of thousands of people begin taking a drug for years do the rare or uncommon serious adverse reactions come to light. Cardiologists are often quoted in the media saying that statins are safer than aspirin, but they are likely unaware that drug trials frequently fail to report all serious adverse reactions. (To see how common it is for drug companies to withhold information about adverse reactions suffered by clinical trial participants, see “Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles.”)

Statin trials are a case in point. James Wright, MD, and colleagues at the University of British Columbia conducted a 2003 review of all five statin primary prevention trials and found that the serious adverse events* went unreported in three of these published trials. When Dr. Wright was asked for an update, he explained by e-mail that the serious adverse events were collected in all 12 major statin trials. However, ten of these trials have failed to report these important results (i.e., make them publicly available). Worse, the authors of these trials refused the UBC reviewers’ repeated requests for the harms data.

Treatment guidelines may be aimed at physicians, but the brunt of their deficiencies will be borne by the people who unquestioningly follow their doctors’ recommendations, especially those who are at low risk of developing heart disease. Understanding the probabilities that relate to the drug as well as your own personal risk is crucial to informed decision-making.

If your doctor says that statin therapy will reduce your odds of having a heart attack by 25% but cannot answer the question—25% of what?—here is how to do it yourself. Go to the National Heart, Lung and Blood Institute Web site for the less than perfect 10-year risk calculator. If, for example, you have a 2% chance of having a heart attack in the next ten years (two out of 100 people with exactly your risks), then the 25% reduction from statin therapy will bring your odds down to 1.5%. Predictably, the quiz, or anything else on this Web site, won’t help you understand the odds of harm or benefit from statin drugs. It is easy to see why pharmaceutical companies like to convey benefit in terms of a 25% reduction in their ads without explaining what that means or how it relates to a person’s baseline risk of having a heart attack. It is much harder to understand why information gathered and disseminated by a government agency funded with taxpayers’ money would not be more forthcoming.

Bottom Line: The new analysis of international guidelines shows a wide variation in the number needed to treat, though all are based on the same clinical trials. Harms are not addressed, possibly because there is a consensus among cardiologists that statins are safe and that serious side effects are rare. But there is also a consensus among people who study the FDA’s postmarketing surveillance system that less than 10% of all serious adverse drug reactions are reported to the agency. Inefficient guideline like those from Canada and the U.S. will send many people to statin therapy who have only a low risk for heart disease. Using the Canadian guidelines, Dr. Manuel and colleagues estimated that at least 23,000 low-risk people would have to take statins for five years to prevent one death from heart disease.

* Defined as “any untoward medical occurrence that results in death, is life-threatening, requires hospitalizations, requires prolongation of hospitalization, or results in persistent or significant disability.”

Maryann Napoli, Center for Medical Consumers ©

Controversy over U.S. Cholesterol-Treatment Guidelines

On July 12, 2004, the U.S. National Cholesterol Education Program updated its statin-treatment guidelines, greatly expanding the pool of candidates for statin drugs. They include men and women without heart disease but who have a moderately high risk of developing it, plus low-density lipoprotein (LDL) levels between 100 and 129 mg/dL; and those with heart disease and LDL levels between 70 and 100 mg/dL. The new recommendations are applied to men and women regardless of age. Overnight, millions more Americans became eligible for life-long statin therapy.

Within days of the announcement, two reporters at Newsday revealed that eight of the nine physicians on the committee that established the new guidelines had strong financial ties to companies that make statin drugs.

Two months later an open letter went to the media and the heads of the National Institutes of Health (NIH) and its division, the National Cholesterol Education Program, calling for the creation of an independent review panel free of conflicts of interest to conduct another review of all the new data from the five studies that led to the updated recommendations. The letter was written by Merrill Goozner of the Center for Science in the Public Interest and signed by 36 physicians, researchers, scientists, and politicians.

The letter charged that the expanded guidelines do not reflect the evidence. Among the objections: the evidence does not support the broad use of statins in women (including those at “moderately high risk”) and people over 70 without heart disease. And there is conflicting evidence about the value of statins to people with diabetes. Additionally, the letter asked whether the lower levels of LDL are justified by the scientific evidence.

A point-by-point response came in a letter from Barbara Alving, MD, NIH acting director, which is also available on the NCEP Web site. A new panel will be formed when results of the ongoing trials are available and the guidelines require another update, wrote Dr.Alving, and future guidelines will be posted in draft form on the National Heart, Lung, and Blood Institute Web site, along with “financial disclosure information.”

Maryann Napoli, Center for Medical Consumers ©

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Vytorin: Yet Another Cholesterol Drug

Posted by medconsumers on February 1, 2006

Vytorin Ads Aimed at Keeping Profits High

“Pay no attention to direct-to-consumer ads for prescription drugs. These are meant to sell drugs, not educate consumers, and they only add to the prices you pay.” Even if you follow this wise advice offered by Marcia Angell, MD, in her acclaimed 2004 book, The Truth About Drug Companies, chances are you will have one of the following drugs prescribed by a physician. They are currently advertised heavily to doctors as well as the general public. Not surprisingly, the most aggressively promoted drugs wind up to be the most frequently prescribed…and the most frequently given out as free samples. In many cases, there are lower cost alternatives.

Vytorin to Lower Cholesterol

When a blockbuster drug is due to lose its patent protection—and blockbuster is usually defined as sales over a billion dollars a year—the drug company must find creative ways to keep the profits high. Vytorin illustrates one path commonly taken by drug companies. This drug is the creation of the pharmaceutical giant Merck, which will soon face competition from cost-cutting generic drug companies when its blockbuster cholesterol-lowering drug, Zocor, goes off patent this year.

Working with another drug company, Schering-Plough, Merck has come up with Vytorin.  Sometimes referred to as the newest statin, the top-selling class of cholesterol-lowering drugs in the world, Vytorin combines an older statin, Zocor (generic name: simvastatin), with a newer cholesterol-blocking drug called Zetia, made by Schering-Plough. To allow plenty of time to sell doctors the idea that they should prescribe a newer, more expensive drug, Vytorin came on the market in 2004—well before Zocor’s patent runs out. Its sales have risen steadily ever since.

How Long Did the Vytorin Studies Last?

People are usually on cholesterol therapy for life; yet the two FDA-required clinical trials lasted only 12 and 23 weeks, respectively. In both trials, participants were randomly assigned to take either Vytorin, a placebo (sugar pill), Zocor, or Zetia. The study participants taking Vytorin showed greater reductions in the so-called “bad cholesterol,” or low-density lipoproteins. Whether Vytorin is better than any other single-ingredient statin drug at reducing the risk of a heart attack or stroke has not been studied.

Cautions:

Statins are great at lowering cholesterol; but they are much less impressive at lowering the risk of heart attack and stroke in people without heart disease. Media reports usually refer to statins as safe or well tolerated. Rarely is it mentioned that virtually all the clinical trials involving statins were conducted by the drug’s manufacturer. And many of these drug trials have failed to release all the data involving adverse reactions. [See the review of primary prevention trials www.ti.ubc.ca, Letter #48.] Therefore, the safety of long-term statin use remains unknown. Even less is known about the safety of the other drug in Vytorin, called Zetia, which works by partially blocking the absorption of cholesterol in the small intestine. Zetia was approved by the FDA in 2002 based on its cholesterol-lowering ability, shown in two trials that lasted only two and eight weeks, respectively.

Alternatives:

Two statins, Zocor and Pravachol, will become available generically this year, and only one, lovastatin (brand name: Mevacor), is already available generically for $1.00 to $1.88 a day, compared with $4.00 a day for the top-selling statin, Lipitor. If you are taking an expensive statin, ask your doctor whether you can switch to generic lovastatin. No long-term head-to-head comparison trial of all six statin drugs has been conducted to determine whether Lipitor is superior to the others in reducing the risk of heart attack or stroke.

Maryann Napoli, Center for Medical Consumers ©
February 2006

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