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Posts Tagged ‘Heart’

Heart surgery 2nd opinion center

Posted by medconsumers on September 22, 2009

For years, we have been reporting the overuse of the coronary artery-opening procedure called angioplasty, aka percutaneous coronary intervention. About one million people in the U.S. undergo this procedure annually; despite the fact that well-designed clinical trials proved that many are in non-emergency situations and can be treated just as effectively with the multiple drug therapy. These are the same drugs, by the way, that most people will be told to take after they’ve had an angioplasty. The procedure, done in non-emergency situations, has a death rate of at least 0.63%.

Lown Cardiovascular Center, Brookline, Massachusetts is the place to go if you want a second opinion about the necessity of angioplasty or coronary bypass surgery. Long-time readers may recognize the name of cardiologist Thomas Graboys, MD, of the Lown Cardiovascular Center, who was frequently quoted in HealthFacts over the years, expressing concern that angioplasty had become a cash cow for many hospitals. In one memorable interview, he said that many symptomless people are scared into undergoing angioplasty after “failing” a stress test and told they are sitting on a “time bomb.” Such people, he said, could have been safely treated with daily aspirin and avoided the procedure.

Dr. Graboys, professor of medicine at Harvard Medical School, first came to our attention in 1992 when he co-authored a seminal study showing that angioplasty can be safely deferred in many people who have been told that the procedure is urgently needed. This and many other studies he co-authored over the years led him to recommend a second opinion when a cardiac catheterization is advised because this diagnostic procedure puts people on the proverbial conveyer belt to having an angioplasty or coronary bypass surgery. Sadly, Dr. Graboys is no longer with the Lown Cardiovascular Center. He was forced into premature retirement in 2006 due to Parkinson’s disease and dementia. He wrote a book about the experience called Life in the Balance.

Visit the Lown Cardiovascular Center Web site to see what a second opinion involves and to read the bios of the six cardiologists on the staff and no cardiovascular surgeons. Let us know if there’s a similar center in your area.

Maryann Napoli,Center for Medical Consumers(c)

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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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Blood Pressure Drugs for All at High Risk, Whether or Not Blood Pressure is High

Posted by medconsumers on June 1, 2009

The typical doctor visit starts with blood pressure measurement, and everyone with a high reading is told to come back again in three months. If blood pressure remains high, one drug or more is the next step, and then three-month follow-up visits continue indefinitely.

A team of British researchers wants to radically change this scenario. Blood pressure lowering drugs should be prescribed to anyone who is at high enough risk to benefit from treatment, whatever their reason for being at high risk and regardless of whether they have high blood pressure or not. What’s more, the British researchers want to change the traditional doctor-visit focus from: has your blood pressure gone down and stayed down? to: is your drug therapy causing any adverse effects?

All blood pressure drugs can dramatically reduce the risk of heart attack and stroke; and all are virtually interchangeable, say the British researchers. Therefore, any tailoring to the needs of the individual would be based on whether the drugs cause adverse effects. Fewer doctor visits would be the result, as well as fewer adverse drug reactions, many of which are currently caused by doses that are too high. Eliminated is the uncertainty many doctors have about which drugs to prescribe and who should be treated.

The proposed radical shift in thinking about blood pressure drugs appeared online last month in the British Medical Journal. Malcolm Law and colleagues based their proposal on an in-depth analysis of the data from 147 blood pressure drug trials published between 1966 and 2007. The trials had a combined total of nearly a half-million participants, aged 60 to 69 years.

Law and colleagues base their conclusions on these trials that compared people with and without heart disease given drugs or a placebo; people with normal blood pressure and high blood pressure (hypertension) with and without drug therapy.  All five classes of blood pressure drugs were represented, as well as differing doses.

Here’s what they found: Any one of the main classes of blood pressure drugs given at the standard dose will reduce the incidence of fatal and non-fatal heart attack by about 25% and stroke by about 33% and heart failure by about 33%. These reductions held up, say Law and colleagues, whether or not the people had heart disease and whether or not they had high blood pressure.

Of course, you would want to know what your risks are for each heart problem if you don’t take any drugs so you can get a clearer idea of what the risk becomes once you do. The British researchers did the math for you based on older people living in England and Wales. At age 65, the risk of having a heart attack (fatal and non-fatal) in the next ten years is about 10% in men and 5% in women. If they go on blood pressure drugs at half dose, the risk in men goes down to 5.4% and in women to 2.7%.

Adverse effects will be minimized with low-dose combination therapy. Cost is dismissed because four of the five drug classes are off patent, and the fifth (angiotensin receptor blockers) will be off patent by the end of this year. “It is difficult to defend the widespread practice of tailoring treatment. The case for individualizing blood pressure lowering disappears with low dose combination therapy based on three drugs; the greater efficacy compared with selective monotherapy or dual therapy avoids the need to choose between drugs,” wrote Law and colleagues.

Some exceptions were found to the all-drugs-are-equally-effective finding. For example, beta blockers [some brand names: Tenormin, Toprol] have an edge over other drugs when given after a recent heart attack; and calcium channel blockers are less effective than other drugs in the risk of heart failure but they had a greater stroke prevention effect than other drugs. Some drugs should be avoided in pregnancy.

Two of its co-authors, Malcolm R. Law and Nicholas J. Wald, made headlines six years ago when they proposed something similar in concept called the polypill. The polypill combines three blood pressure drugs at half the standard dose, a statin, folic acid, and aspirin. At the end of their new research paper, Law and Wald acknowledged that they had “competing interests” (i.e., conflicts of interest) because they hold patents “on the formulation of a combined pill to simultaneously reduce four cardiovascular risk factors, including blood pressure.”

Their research paper is bound to reignite a worldwide debate among doctors about the use of drugs for prevention. What’s needed now is the release of all data used in the new meta-analysis of blood pressure lowering drugs so that an additional critical analysis can be conducted by a team of researchers without competing interests.

There may be strong reasons against the idea that the benefits outweigh the risks for everyone on blood pressure drugs. For starters, the implication that adverse drug effects are banished with low doses has already been disproved in low-dose aspirin studies. No matter how low the dose in these studies, the cases of gastrointestinal bleeding are higher in the people taking low-dose aspirin than in the people taking a placebo. This is true of the Women’s Health Initiative in which the study participants were taking only 100 mg aspirin every other day.

For more information
The May 19, 2009 issue of the British Medical Journal “Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomized trials in the context of expectations from prospective epidemiologic studies.”

Maryann Napoli, Center for Medical Consumers© June 2009

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Drug-Coated Stent No Riskier Than Bare-Metal Stent, But…

Posted by medconsumers on June 1, 2009

Drug-coated stents, intended to keep coronary arteries from closing up again, have been under suspicion for causing harm to people years after they had an artery-opening procedure. In earlier studies, the powerful drugs used to coat the tiny wire-mesh cylinders known as stents, were linked to a slightly higher rate of death and potentially fatal blood clots. A new study of Swedish people who were implanted with either a bare-metal stent or a drug-coated stent appears to exonerate the latter.

While this is good news for people who already had a drug-coated stent implanted, it should not distract from the fact that too many Americans continue to undergo artery-opening procedures for non-emergency heart conditions that can be just as successfully treated with drugs alone.

The Swedish study was led by Stefan K. James, MD, Uppsala University Hospital, and published last month in The New England Journal of Medicine. It is based on the information reported to a nationwide registry of all people in Sweden implanted with either a bare-metal or drug-coated stent between 2003 and 2006 (nearly 48,000). Registry studies represent real-world care; whereas clinical trials are likely to deliver what is thought of as exceptionally good care, i.e., highly experienced surgeons at academic teaching hospitals operating on patients with the best prognoses.

The Swedish study found that the 1- to 5-year results from the registry patients were the same, regardless of the type of stent implanted. There was only one advantage to the drug-coated stent. The treated artery is less likely to become constricted again (restenosis). This advantage, however, was slim. Dr. James and colleagues described it this way, “The rate of restenosis at one year was low for both types of stents and was 1.5 percentage points lower with drug-coated stents than with the bare-metal stents.”
Dr. James was asked by e-mail who is an appropriate candidate for a stent, given the fact that researchers now know that a constricted artery does not indicate the location of a future heart attack. “You are correct,” he responded. “The use of the drug-coated stent should be reserved for patients at high risk for restenosis, such as diabetics.” Dr. James explained that there is also a role for drug-coated stents for people with long and very narrow constrictions, less than 3mm in diameter, in the coronary arteries.

The Swedish study illustrates the importance of following people for years after a surgical procedure to see how they fare. Earlier research from the Swedish registry, also published in The New England Journal of Medicine, indicated that people implanted with drug-coated stents had a 30% higher mortality rate. This landmark study, published in 2005, alerted doctors for the first time that the drugs used to coat the stents were causing a slightly increased risk of death and potentially fatal blood clots. It generated attention around the world and many cardiovascular surgeons changed their practice accordingly. Now surgeons start their patients on Plavix prior to surgery and continue the drug long after implantation of a drug-coated stent.

Bottom Line: Stents were first introduced to stop the high rate of restenosis that occurred after a coronary artery-opening procedure, also known as angioplasty. When it was discovered that tissue growth around the implanted stent also caused restenosis, the drug-coated stent was introduced. Some stents are coated with paclitaxel, an anti-cancer drug that has anti-inflammatory effects and others with sirolimus, an immunosuppressive drug. When the 2005 Swedish registry study indicated that the drugs used to coat the stent increased the risk of dangerous blood clots, Plavix, was introduced into the mix. Plavix (generic name: clopidogrel), heavily promoted on TV, has its own risks, primarily stomach or intestinal bleeding and ulcers of the stomach or intestines.

For decades, people have been told that large constrictions in the coronary artery signal future heart attacks which must be prevented by an immediate artery-opening procedure called angioplasty. This hypothesis was disproved 3 years ago by two landmark trials.  Many, if not most, of the one million or so Americans who undergo angioplasty each year (with or without stents) can be treated just as successfully with the same multiple-drug regimen advised for just about everyone after angioplasty.

The exception: People in the midst of a heart attack are appropriate candidates for angioplasty. Unfortunately, about one-third of all heart attack patients do not receive artery-opening treatment within the recommended 12 hours after the first symptoms of a heart attack.

More Information About the Two Landmark Trials:
Heart attack patients who did not receive the recommended treatment in time are represented in the federally-funded Occluded Artery Trial (OAT). This trial, published in 2006 in The New England Journal of Medicine, randomly assigned people who were in stable condition 3 to 28 days after a heart attack to have either an artery-opening procedure with stenting plus multiple-drug therapy or multiple-drug therapy alone. After 3 to 5 years, the people given multiple-drug therapy alone did just as well as the people who underwent an artery-opening procedure plus drugs.

The OAT found no benefit to opening a blocked artery after the heart attack patient is stabilized. The procedure “should be reserved only for certain patients such as those who are unstable or continue to have chest pain following a heart attack,” according to an OAT researcher. See 2006 press release.

In 2007, another landmark trial, known as COURAGE [Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation], produced results similar to those of OAT for people with stable heart disease. The people in this trial had angina (average 10 episodes a week) for about two years before they entered the trial; most had hypertension, over one-third had had a heart attack.  In short, they were at very high risk and were highly symptomatic for a long time prior to the start of this trial.  A five-year follow-up showed that those who were randomly assigned to have angioplasty had the same risk of heart attack and death as those who were randomly assigned to multiple drug therapy.

Maryann Napoli, Center for Medical Consumers© June 2009

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Radiation dose of cardiac CT scans

Posted by medconsumers on April 15, 2009

A CT scan of the coronary arteries is a good diagnostic tool, but it involves a large dose of radiation. To determine how much radiation is involved in cardiac CT scans (also known as computed tomography angiograms), researchers accessed data from 1,965 CT scans of the coronary arteries performed in 50 hospitals around the world. The average estimated dose was 12 mSv, which is the equivalent of 600 chest x-rays, although estimated exposures varied widely from place to place (5 mSv to 30 mSv).

The sixfold difference was caused by variations in CT scan protocols, hardware, and use of established strategies to minimize radiation exposure. One of them, called electrocardiographically controlled tube current modulation, or ECTCM, is well supported by evidence and is associated with a 25% reduction in radiation dose. Sequential scanning and low voltage scanning were mentioned as other effective options for limiting exposure. Only a minority of patients in this study, however, were scanned using either strategy.

Protecting patients from radiation is one of the basic principles of radiology, say the authors of this study, “Effective strategies to reduce radiation dose are available but some strategies are not frequently used.”

JAMA 2009;301:500– 7

For more information about radiation exposure from CT scans, click into our 2009 article, “CT scans—lots of radiation, little research.”

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Generic Heart Drugs Just As Good

Posted by medconsumers on February 1, 2009

Generic Heart Drugs Just as Good as Brand-Name Drugs

Buying prescription drugs under their generic names can save a substantial amount of money, but the perception lingers—among doctors and consumers alike—that brand-name drugs are superior. To determine the accuracy of this prevailing view, a team of reviewers assessed all the studies that compared generic and brand-name heart drugs and found a major contradictory force at work. Although the studies produced no evidence that generic drugs are inferior, many of the medical journal editorials that accompanied these studies urged against their use.

First, it must be said that the FDA requires all generic drugs to be proven bioequivalent to their brand-name counterparts before they are allowed on the market. This means that they must be chemically equivalent in terms of the active ingredients of the brand-name drugs. However, generic drugs may differ in terms of their inactive ingredients like color and shape of the pill, fillers and inert binders. Generic drug manufacturers are not required to replicate the original effectiveness trials. Brand-name drugs are expensive until their patents run out. Once that occurs, other companies are free to produce lower cost generic versions of the same product.

38 Trials in the Review
For their new review, Aaron S. Kesselheim, MD, and colleagues at Harvard Medical School, assessed 38 trials that had randomly assigned people to take either a brand-name heart drug or its generic equivalent. Nine different classes of cardiovascular drugs were studied, including drugs to lower cholesterol and blood pressure and drugs that stabilize heart rate.

Most of the studies (6) involved warfarin, the blood thinner that doctors identify as having a narrow therapeutic index, which describes the difficulty of calibrating the correct dose—too high can cause internal bleeding and too low can result in fatal blood clots.

The reviewers’ conclusion: “Whereas evidence does not support the notion that brand-name drugs used in cardiovascular disease are superior to generic drugs, a substantial number of editorials counsel against the interchangeability of generic drugs.”

Kesselheim and colleagues came up with two educated guesses about the contradictory advice from the doctors who wrote negative editorials. 1) “Physicians’ concerns are based on anecdotal experience;” 2) “The conclusions may be skewed by financial relationships of editorialists with brand-name pharmaceutical companies, which are not always disclosed. Approximately half of the trials in our sample and nearly all of the editorials and commentaries did not identify sources of funding.”

Dr. Kesselheim was asked by e-mail whether his results say anything about generic versions of other drugs. “Well, our study only looked at drugs used in cardiovascular disease, so anything I’d say about other fields of medicine would be outside of the bounds of what we specifically looked at.,” he responded. “Still, for nearly every other field of medicine, I would not expect the results to be substantially different, given the positive experience of millions and millions of patients over the years who take generic drugs for psychiatric, rheumatologic, endocrine, etc. reasons.”

This review was published in the December 3, 2008 issue of the Journal of the American Medical Association and was funded in part by the Attorney General Prescriber and Consumer Education Grant.

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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Vitamins: Research Shows No Benefit and Some Risks

Posted by medconsumers on December 1, 2008

Vitamins Don’t Work: Research Continues to Find No Benefit and Some Risks

Looking for ways to save money? Stop taking vitamins. The scientific case against them has been building over the last few years, starting with the report from the 2006 U.S. National Institutes of Health State-of-the Science Conference on Multivitamins/Mineral Supplements. The next year, a Cochrane review of all antioxidant trials caused an uproar because it found no preventive benefit to taking these supplements and a slight increase in mortality. And just in the last month alone, one new trial found no cancer preventive benefit to taking B vitamins; and another trial found no cardiovascular preventive effects for vitamins C and E. Both were published in the Journal of the American Medical Association.

B Vitamins
The B vitamins trial was led by Shumin M. Zhang, MD, and colleagues at Brigham and Women’s Hospital in Boston and Harvard Medical School. The impetus for this trial, explained the researchers, was the prevailing idea that folate, vitamin B6 and vitamin B12 might play an important role in cancer prevention. Yet the researchers also noted that information from earlier trials of folic acid alone or in combination with B vitamins have produced mixed results, and one trial “even raised concerns about deleterious effects.” What’s more, women were underrepresented in these trials.

Zhang and colleagues recruited 5,442 female health professionals, aged 42 years or older with cardiovascular disease or three or more risk factors for heart disease. All were randomly assigned to take a placebo or a daily supplement that combined 2.5 mg of folic acid, 50 mg of vitamin B6 and 1 mg of vitamin B12.

After seven years, the women taking the combination supplement had the same rate of cancer as those taking a placebo. This trial was funded by a grant from the U.S. National Institutes of Health.

Vitamins E and C
The other new trial found that vitamins E and C did not prevent cardiovascular disease in healthy men, aged 50 and older. The Physicians’ Health Study II involved 14,641 male physicians, 5% of whom had cardiovascular disease at the start of the trial. The men were randomly assigned to take 400 IU of vitamin E every other day and 500 mg of vitamin C daily or a placebo.

After a mean follow-up of eight years, the supplements had not reduced the risk for heart attack, stroke, death, heart failure, angina or the need for a coronary artery-opening procedure. Worse, vitamin E was associated with an increased risk for hemorrhagic stroke, or bleeding in brain (39 hemorrhagic strokes in the men taking vitamin E, compared with 23 in those taking a placebo). The negative results shown for vitamin E confirm those from earlier studies that involved men and women with preexisting cardiovascular disease.

This trial was led by Howard D. Sesso, ScD, Harvard School of Public Health, and funded by grants from the National Institutes of Health, the BASF Corporation, Wyeth Pharmaceuticals, and DSM Nutritional Products Inc (formerly Roche Vitamins).

Earlier Vitamin Research:
These two new trials are but a small part of the research that has found vitamins do not prevent illness or prolong life. Far more extensive is the following government report about multivitamins and the Cochrane review of antioxidant trials mentioned at the beginning of this article.

The report from the 2006 NIH State of the Science Conference on Multivitamins/Minerals for the Prevention of Chronic Conditions. A panel of experts was charged with the task of reviewing all placebo-controlled trials designed to see whether multivitamins and/or minerals can prevent cancer; age-related sensory loss; and cardiovascular, endocrine, neurologic, musculoskeletal, gastroenterologic, renal and pulmonary diseases. This is the report’s conclusion:

In systematically evaluating the effectiveness and safety of multivitamins and/or minerals in relation to chronic disease prevention, we found few rigorous studies on which to base clear conclusions and recommendations. Most of the studies we examined do not provide strong evidence for beneficial health-related effects of supplements taken singly, in pairs, or in combinations of 3 or more.

Within some studies or subgroups of the study populations, there is encouraging evidence of health benefits, such as increased bone mineral density and decreased fractures in postmenopausal women who use calcium and vitamin D supplements. However, several other studies also provide disturbing evidence of risk, such as increased lung cancer risk with beta-carotene use among smokers.”

The updated 2008 Cochrane review: “Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases.” The 68 placebo-controlled trials included in this review attempted to answer these questions: Can antioxidants prevent disease in healthy people? Can they prevent recurrences in people with cancer, heart disease or other illnesses?

This is the Cochrane review’s conclusion:

We found no evidence to support antioxidant supplements for primary or secondary prevention. Vitamin A, beta-carotene, and vitamin E may increase mortality. Future randomized trials could evaluate the potential effects of vitamin C and selenium for primary and secondary prevention. Such trials should be closely monitored for potential harmful effects. Antioxidant supplements need to be considered medicinal products and should undergo sufficient evaluation before marketing.

Funding Questioned: When this Cochrane Review was first published in 2007, we reported its findings and addressed one of the strongest criticisms leveled against it. Many suspected that the review was funded by the pharmaceutical industry to counteract public enthusiasm for vitamins. In our 2007 article on this topic, one of the review’s co-authors was asked about the funding: Christian Gluud, MD, of the Cochrane Hepato-Biliary Group, Rigshospitalet, Copenhagen University Hospital, responded, “The sole sponsor of this review is the Copenhagen University Trial Unit, a publicly funded, not-for-profit clinical research center, and about 90% of the trials in this review were funded by companies that make vitamins.”

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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You Can Be Fat and Fit

Posted by medconsumers on April 1, 2008

Walk More—That’s all you have to do

For cardiovascular and other health benefits like increased longevity, you need only exercise moderately for 30 minutes at least five days a week. That has been the recommendation for nearly 15 years, and it has decades of high-quality research to back it up. In an attempt to refine things further, a team of researchers asked the questions: Can this exercise recommendation be cut back further and still produce health benefits? Will 45 minutes five days of the week provide even more?

The study designed to answer these questions drew participants from the most sedentary segment of the U.S. population—postmenopausal women. Published last year in the Journal of the American Medical Association, this study continues to produce surprise findings as researchers are still analyzing the mountains of data it has generated.

A co-author of this and many other landmark studies is exercise scientist Steven N. Blair, PED, professor in the Department of Exercise Science at the University of South Carolina. One of the world’s leading researchers on the health benefits of exercise, Dr. Blair is interviewed by Maryann Napoli.

MN: Is it fair to summarize your research as providing proof that people can be fat and fit and that they can achieve cardiovascular fitness with only a moderate degree and amount of activity?

SNB: Scientists try to stay away from using the word “proof”, but we have provided pretty compelling evidence that you can be fat and fit—just as you can be thin and unfit. And that fitness provides important protection from many chronic diseases and premature mortality even in people who are obese.

MN:
And it need not be vigorous exercise.

SNB: To attain what we’ve labeled “moderate fitness”—that is, if one follows the recommendation of 30 minutes of moderate intensity activity, such as walking on five or more days a week, you will develop a level of fitness that is protective.

MN:
Must it be done in 30 consecutive minutes?

SNB: You can do it in separate segments—in bouts of at least ten minutes or more. The evidence for that has accumulated since we first made that recommendation back in the mid-1990s. It’s clear that whether you do 30 minutes of walking in three ten-minute bouts or two 15-minute bouts or all at once, the physiologic benefits are identical.

MN: That would also cut down on injuries.

SNB:
It’s clear from our studies—and those of others—that as the amount and the intensity of the exercise goes up, the risk of injury does as well. The injury rate associated with moderate-intensity activity is incredibly low.

MN:
How fast should people walk?

SNB:
Walk purposefully as if you were going to a meeting—about 3 miles per hour, or 20 minutes a mile—but that will vary a bit depending on a person’s age, fitness, and health status. Some will need to walk a bit slower, especially when starting a program, and more fit individuals may walk at a faster rate.

MN: Why is it that those cardiac risk calculators that doctors use to determine an individual’s chance of having a heart attack in the next ten years do not include a question about physical activity? I’m referring to “risk assessment tools” like the one from the National Heart, Lung and Blood Institute that ask questions about blood pressure, cholesterol, etc. to identify who should be on drug therapy.

SNB:
That calculator is largely based on the Framingham Heart Study [initiated 60 years ago], and they have never incorporated fitness. I tell physicians if you use the Framingham risk score to characterize your patients’ risk, you’re not finished with the job, unless you also have a measure of fitness or at very least, take a careful physical activity history.

MN: Why do you think the public continues to be told that excess weight will cause premature death and heart attacks? Three years ago, researchers at the Centers for Disease Control and Prevention (CDC) published a study that showed people who are overweight or even obese do not have shortened life spans. Decreased mortality was shown only at either end of the spectrum—the morbidly obese and the very thin.

SNB:
Some people are dedicated to a concept that being overweight is hazardous to your health and they have an unwillingness to look at the actual data. When you look at the work of Katherine Flegal who headed that CDC study, you will see that she found that overweight is not the hazard for mortality as it has been made out to be, and it may even be protective. She used the best available data, such as that from the National Health and Nutrition Examination Surveys, which are broadly representative of the U.S. population. Yet there are people who have been vehement in their unrelenting criticism of Katherine and her work.

MN: Your work is focused on cardiovascular benefits, but weight loss motivates most people to exercise. I want to talk about a weight-related finding from your latest study that included 464 postmenopausal women who were sedentary, overweight or obese but basically healthy when they were randomly assigned to one of three exercise groups or the control group. This finding surprised me: After six months, “There were no differences in weight or body fat percent across the groups at follow-up but waist circumference was significantly smaller in all three exercise groups compared with the control [no exercise] group.”

SNB: That finding was not a surprise to anyone who works in this area. My colleague Bob Ross from Queen’s University in Kingston, Ontario has done more work on exercise and visceral adiposity than just about anyone. Bob said, “If you get people exercising, the visceral fat is going to go.” What we saw [in our study] was no difference in weight change across those four groups, yet all three exercising groups lost waist circumference, presumably visceral fat, compared with the control group.

MN: It should be pointed out here that one important aspect of your study is the fact that the women in the exercise groups performed their exercise routines under observation in the laboratory, thus bypassing the unreliable self-reporting that so often characterizes physical-activity studies. Your study measured what researchers call “dose response,” i.e., whether any health benefits were gained or lost by going lower or higher then the standard recommendation of 30 minutes five days a week of moderate exercise. Any other surprises?

SNB: I was a little surprised that the high-dose exercise group [225 minutes of exercise a week] did not lose more weight because they were doing three times the amount of exercise per week as the low-dose exercise group [72 minutes a week].

MN: What are you working on now?

SNB: We continue to analyze data from our study. When we looked at weights that were measured weekly in all the women, there are some fascinating findings there that I cannot talk about because we have not yet published our findings. It’s based on the notion promoted by the U.S. dietary guidelines 2005, which state, in order to prevent weight gain or promote weight loss, 60 minutes of activity a day is needed. Others have been trumpeting similar ideas. Well, if that’s the case, then the women in our high-dose exercise group should have lost a good bit more weight than the women in the lowest exercise group. We didn’t see that.

MN: Any idea why?

SNB: I’m not sure we’re ever going to know, but it is an area of research that cries out for more study—to try to understand where exercise fits in relation to weight management.

MN: The exercising study participants may not have lost weight, but regular testing of their cardiovascular/respiratory fitness during the study showed that they improved according to the amount of exercise they were assigned to perform.

SNB: Yes. As you see from our study there was a strong positive dose-response relationship for VO2 peak across the control and the three doses of exercise. Even the women in the lowest exercise group significantly improved their cardiovascular/respiratory symptoms and they only did 72 minutes of moderate intensive exercise a week. I’m coming to the conclusion that doing anything is better than nothing. I should be standing up right now while I’m talking with you.

MN: The blood pressure reductions in all three exercise groups were pitifully small.

SNB: Yes, I had expected exercise to show a dose-response gradient for blood pressure.

MN: You mean that you had expected the women doing the highest amount of exercise to have larger reductions in blood pressure.

SNB: Yes, the women were mildly hypertensive at the start of the study but all the exercise groups lowered their blood pressure only a few millimeters of mercury.

MN: There are still many proponents of vigorous-intensity exercise out there. I read that you used to be one of them until your own studies showed the health benefits of moderate-intensity exercise. I also read that you continue to enjoy running. Do you think that one day researchers will find that there are more health benefits to be gained with an intensive exercise routine?

SNB: Perhaps there might be some additional health benefits shown for vigorous exercise, but I frankly think the jury is still out on that one. I’m willing to go out on a limb here and say that doing something is better than doing nothing.

Maryann Napoli, Center for Medical Consumers ©

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