Drugs to prevent heart problems

Congratulations to the two cardiologists who went public with crucial information rarely explained to the public. Their target: Heart drugs prescribed to healthy people who are expected take them every day for the rest of their lives. Guess what? These drugs can be great at improving your blood test results but not so great at helping you live longer or delaying the symptoms of heart disease. (And isn’t that the point, after all?) Billions of dollars were spent annually on drugs that, initially, showed promise that didn’t hold up with long-term scientific scrutiny.  And too often, failure to prove any benefit does not dull the prescribing enthusiasm.

Vinay Prasad, MD, Northwestern University, Chicago, and Andrae Vandross, MD, Yale University, cite examples of widely prescribed drugs that were ultimately proven useless (Tricor),  dangerous (extended-release niacin), or their advantage is uncertain (Zetia, Vytorin).  In the current issue of Archives of Internal Medicine, the two cardiologists propose “setting the bar” higher for drugs prescribed to healthy people. This means clinical trials with a large number of healthy adults who are randomly assigned to take either the new drug or a placebo and are followed for many years. In other words, drug makers should prove their products can cut the rate of death, heart attack, stroke before the drugs are approved for healthy people.

As things stand now, drugs are usually approved after a few months of study on the basis of short-term results.  For example, a drug must be better than a placebo at lowering cholesterol, or blood pressure, etc.  It has long been assumed that this, in turn, will ultimately lower the rate of deaths from heart attack, stroke, etc.  This assumption hasn’t always panned out. This was shown in 2006, when a much-anticipated drug called torcetrapib was in the process of getting FDA approval for its ability to greatly increase the so-called good cholesterol. But the clinical trial had to be stopped because the drug also increased the number of deaths and heart problems.

Occasionally, the large clinical trial proposed by the two cardiologists is, in fact, conducted—-but the results aren’t in for a decade or two after the drug was approved.  Worse, prescriptions continue to rise for a drug found to be useless.  One widely prescribed drug called fenofibrate (some brand names: Tricor, Lipofen, Antara) was approved by the FDA in 1993 for the treatment of very high triglycerides in the blood. Tricor became a blockbuster four years after a 2005 meta-analysis cast doubt on the benefits of all drugs in this class known as fibrates. There were no improvements in overall survival, and this was confirmed in a landmark clinical trial. “Although it was prescribed for more than a decade to further improve lipid profiles [standard test for fats in the blood] for patients already prescribed a statin, we now know the error of this practice.”

Cost is no small matter, as noted in this paper. “Annual spending on statins exceeded $19 million in 2005, ezetimibe (in the form of Vytorin and Zetia) costs over $5 billion in 2007, and fenofibrate costs passed $1 billion in 2009.”

Another improvement suggested by Drs. Prasad and Vandross:  Drugs given to healthy people must be shown to lower the rate of deaths from all causes before they are approved.  Too often a drug will lower the rate of heart-related deaths but not the total rate of deaths. If the drug succeeds with the former but not the latter, this raises the possibility that the drug itself is killing some people.  The only way to rule this out is to demand that the clinical trials not only keep track of heart-related deaths but also total deaths.

If this sounds familiar, it is the same argument that has emerged over how to prove the lifesaving value of screening tests (also “prescribed” for healthy people). “While screening for breast, prostate, and colon cancer decreases cancer-specific death, none [emphasis added] have shown an overall mortality benefit in prospective trials,” wrote the two cardiologists.  Screening can lead to potentially fatal, unnecessary, aggressive cancer treatments.  click here for breast cancer screening,  here for prostate cancer screening, and here for colorectal cancer.

Whether these excellent proposals ever see the light of day remains to be seen.  After all, the current system of short-term pre-approval trials serves drug industry interests, and healthy people in early middle age are its favorite “market share.” (Unlike the sick and the elderly, healthy people have a longer lifespan ahead in which to take drugs.)  It’s a good idea to think long and hard before accepting “preventive” drug therapy if you don’t have heart disease.  Drs. Prasad and Vandross have given us the blueprint for the issues to be raised with the prescribing doctor.

Maryann Napoli, Center for Medical Consumers©

Related posts

Drug to prevent heart attacks and strokes

Drugs that can cause leg cramps

Painful cramps in the legs or feet that disrupt sleep are impervious to treatment. The use of magnesium supplements and daily stretching exercises have been proven ineffective. And the anti-malaria drug Quinine, though often prescribed, is both dangerous and unproven. A team of Canadian researchers have identified several widely used prescription drugs that are a likely cause of these severe muscle contractions.

The new study, which was conducted in the province of British Columbia, used an ingenious way of sorting out the drugs most likely to trigger leg cramps. They fall into three frequently prescribed drug classes—diuretics for heart failure and hypertension, cholesterol-lowering statin drugs, and inhaled long-acting β2-agonists for the treatment of asthma and chronic obstructive pulmonary disease. The study, entitled “Nocturnal Leg Cramps and Prescription Use That Precedes Them,” was led by Scott R. Garrison, MD, University of British Columbia, Vancouver, and  published recently online in Archives of Internal Medicine.

In Canada and the U.S., doctors frequently prescribe Quinine for nighttime leg cramps, though the drug has never been proven effective for this purpose. Most government drug regulatory agencies, including the U.S. Food & Drug Administration, have issued warnings against the use of Quinine for leg cramps because of severe, potentially fatal adverse effects. Still, the practice lives on in both countries. Quinine was the first effective treatment for malaria.

Since British Columbia is not a hotbed of malarial disease the researchers focused their attention on Quinine prescriptions, stating that they could be reasonably certain that the drug was prescribed “almost exclusively” for the prevention of leg cramping.

Thanks to two databases maintained by this province, the researchers had access to information on all prescriptions dispensed and all physician services and hospitalizations paid by its taxpayer-supported health care system. The third database included all vital statistics such as date of death for the period between 1996 and 2009. The study was funded by the government of British Columbia.

The researchers began the sorting-out process by confining their study to people over the age of 50 years because nocturnal leg cramps are uncommon in younger adults. Then they singled out the people given first-ever Quinine prescriptions between 2001 and 2006. After that, they worked backward to see whether some drugs were prescribed more frequently in the years leading up to the Quinine prescriptions. The provincial databases allowed for comparison of similar populations who did and did not receive Quinine prescriptions.

Here’s what the researchers found: Of the three drug classes with the strongest link to leg cramps, statin drugs had the weakest association. Statins are known to cause muscle symptoms, but myopathy (muscle weakness) is more likely than cramps.

The two drug classes with the strongest links to leg cramps are the diuretics and the inhaled long-acting β2-agonists (some brands: Advair, Serevent, Symbicort). Quinine was substantially more likely to be (mis)prescribed in the year following a prescription from one of these two drug classes. When the researchers broke things down further in the diuretic class, which has a wide range of brand names and three subgroups, the potassium-sparing diuretics (some brands: Aldactone, Dyrenium, Midamor) and thiazidelike diuretics (Zytanix, Zaroxolyn,  Mykrox) were even more likely to cause leg cramps than loop diuretics.

The researchers explained why they thought of leg cramps as a drug side effect. For starters, they are common to people over the age of 50 years, and this is the same group likely to be on multiple drug therapy. “Instead of stopping the drug likely to cause the leg cramps many doctors are inclined to prescribe yet another drug in the hope of stopping the leg cramps.”

What should people do if they have leg cramps and are taking one of the drugs most likely to be the cause?  Dr. Garrison, the lead author of this study, answered this question by e-mail,  “Nocturnal leg cramps can be very difficult to treat. If someone suffering cramps is on either an inhaled beta-agonist  or a potassium-sparing diuretic they should ask their doctor if other treatment options could be considered. Is drug treatment for their condition essential? If so, inhaled anticholinergics are a good alternative to beta-agonists that do not promote cramps, and their doctors will know many alternatives to diuretics for the treatment of high blood pressure.”

Maryann Napoli, Center for Medical Consumers©

Niacin and the heart

Niacin, in very high doses, has long bridged the gap between mainstream and alternative medicine.  Many people with heart disease regularly take this form of vitamin B to prevent a first heart attack or avoid having another one.  Though niacin is available over the counter, the more expensive  branded product called Niaspan is often prescribed by cardiologists as the better way to raise blood levels of  “good cholesterol” (high-density lipoprotein).  The assumption that raising HDL cholesterol with niacin will spare anyone a heart-related disaster, however, had never been put to a good scientific test.  That is, until now.

In May, the first large clinical trial designed to determine whether high-dose niacin can benefit people with heart disease had to be stopped 18 months earlier than planned.  Reason:  The addition of Niaspan to the usual statin drug therapy given to heart patients did not lower the chances of having a heart attack or a stroke.   All 3,414 study participants, whose average age was 64 years, had been randomly assigned to take either Niaspan (extended release niacin, 1500-2000 mg daily) or a placebo.

Another, more alarming, reason why this trial was stopped early can be found in the press release issued on May 26, 2011 by its funding source, the National Heart, Lung, and Blood Institute, “…a small and unexplained increase in ischemic stroke rates” was noted in the participants taking Niaspan. This might come as a surprise to many people.  After all, niacin is a vitamin—vitamin B₃ to be exact.

Now, the final results of this halted trial, known by the acronym AIM-HIGH, were published recently in The New England Journal of Medicine:  “Among patients with atherosclerotic cardiovascular disease, … there was no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up period, despite significant improvements in HDL cholesterol and triglyceride levels.”  In other words, the heart patients taking Niaspan had greater improvements in their blood test results, compared to the heart patients who were not taking niacin.  But there was no difference between the Niaspan group and the placebo group in terms of outcomes such as heart attack, stroke, and the need for heart surgery.

As for the increased rate of ischemic stroke shown in the study participants taking Niaspan, this was acknowledged by the authors of the AIM-HIGH trial as unexpected but possibly due to chance.  “Although the number of ischemic strokes was higher in the niacin group, the overall rate was low, and we cannot be certain whether this observation reflects a causal association or possibly the statistical ‘play of chance’.”

The AIM-HIGH trial’s additional funding support was described this way in The New England Journal of Medicine: “Abbott Laboratories [maker of Niaspan] provided additional support from an unrestricted research grant.  Merck donated the simvastatin [taken by all the study participants].  The companies that provided financial support or products had no role in the oversight or design of the study or in the analysis or interpretation of the data.”

You might wonder what made cardiologists so enthusiastic about niacin in the first place.  A 2009 Forbes magazine article reported their reactions in response to a small clinical trial (only 208 heart patients) announced at the annual meeting of the American Heart Association.  Using ultrasound in this trial funded by Abbott Laboratories, researchers showed that Niaspan was better than statins alone at clearing coronary arteries.  (Niaspan, by the way, hit $254 million in annual sales in 2009. And Abbott is a “funding partner” of the American Heart Association, as noted on its website.)

Unlike the newly published AIM-HIGH trial, the statins vs. Niaspan/ultrasound trial did not look at outcomes that were meaningful to heart patients.  Cleared arteries or increased HDL levels may be promising, but it is heart attack, stroke, or a heart-related early death that people are trying to avoid.  The AIM-HIGH trial looked for these and other outcomes but found none; the ultrasound study did not even look at outcomes.  The latter is a more common scenario.

When told to go on long-term drug or vitamin therapy, it’s a good idea ask the prescribing doctor about proven outcomes.  The AIM-HIGH trial showed that raising the HDL cholesterol can only improve a lab test result.  Too often doctors give their patients the impression that this is the goal.  It isn’t.

Maryann Napoli, Center for Medical Consumers©

Related articles

Lower salt intake will reduce blood pressure but not heart attack risk:  read more

Low fat diet: Whatever happened to that advice?    read more

Sunscreens can protect against sunburn, but they have yet to be proven to prevent cancer.   read more

The end of cholesterol…

It’s somewhat like observing the first signs of spring. Lipitor, the last of the block-buster cholesterol-lowering statin drugs, is about to go off patent, so you look around for signs that the affected drug companies have found a way to keep revenues up. Lovaza, a prescription-only capsule of omega-3 fatty acid may well fit the bill. It’s time to scare us about another blood lipid — triglycerides. After all, the statin drugmakers have gone about as far as they can go with the dangers of high cholesterol.

“Very high triglycerides [TG], or too much fat in the blood, are a “very serious medical condition,” say the Lovaza ads. Then comes the scary but vague, “having too many triglycerides in your blood may lead to future health problems.” And here’s the best part: “Lavaza has not been shown to prevent heart attack or stroke.” (Occasionally, the FDA requires drug ads to be honest.)

Are high TG really dangerous to health? “Not particularly is the short answer,” responded cardiologist Vikas Saini, MD, president of the Lown Cardiovascular Research Foundation,  which is affiliated with the unique second-opinion consultation center near Boston. In a telephone interview, Dr. Saini explained that when you pool the results of observational studies, there may be a little extra risk to having very high TG, but no one knows whether lowering TG will reduce the risk of cardiac events. Usually, elevated TG comes with high blood sugar and low HDL (good) cholesterol, so it’s hard to tease out the independent effect of TG alone. “I view high TG as a signal that that a patient’s energy balance is out of whack. In the vast majority, high TG is due to inactivity, weight gain, and a diet too high in carbs, specifically simple sugars and sweets.”

The statin drugmakers have always given lip service to lifestyle changes, knowing full well that many of us would prefer to pop a pill. The statin companies already made a bundle successfully marketing a drug that benefits only a tiny minority who take it (click here) and are unlikely to walk away from the goldmine without finding some way it can be reworked into another goldmine. One company has already tried—and failed—to get the FDA to allow the sale of its statin over-the-counter. (The FDA sees this as too risky without doctor supervision, but it could come around as pressure to reduce drug costs intensify.)

GlaxoSmithKline (GSK), maker of Lovaza, seems to have another plan. First, it can rightfully claim to be the only producer of fish oil capsules to have tested its product against a placebo to the FDA’s satisfaction. And as of four years ago GSK bought the right to make a generic version of the statin Mevacor after it lost patent protection.

GSK is positioning itself to produce a combination statin/fish oil drug and has already passed the FDA-required tests. (Agency standards aren’t all that rigorous; approval was based on two trials that went no longer than 16 weeks and showed TG went down and LDL cholesterol improved.) Once the combination drug becomes available, all GSK has to do now is make us think that purchasing its costly fish oil plus a statin in one pill is more convenient than taking them separately.  And perhaps an insurance company or two will pay a portion of the tab. This wouldn’t be the first time an off-patent statin was reworked into an expensive combination drug.  Remember Vytorin?   (See “Why is anyone taking Zetia or Vytorin?”)

“Fish oil is good,” says Dr. Saini, “but as a prescription drug [Lovaza] is likely to be more expensive than the over-the-counter fish oil capsules and/or eating fish high in omega-3 fatty acid [blue fish, mackerel, lake trout, anchovies, etc.], but then again I haven’t done any price comparison.”

Yes, but.   As with all dietary supplements, fish oil supplements do not have to meet any quality standards. The companies that make fish oil supplements are not required to conduct clinical trials to prove safety, effectiveness, or even that the product actually contains fish oil.  We can thank GSK for its tests which showed that the adverse effects like belching, indigestion and taste perversion, occurred in 3% more of the people on Lovaza, compared with those on the placebo. And the FDA-required label for Lovaza warns of fish oil’s potential effect on prolonged bleeding, advising physicians to monitor people taking anticoagulants or other drugs affecting coagulation (e.g., aspirin, NSAIDs, warfarin, Coumadin).

If you want to take a fish oil supplement, see which products were found to be the most trustworthy, according to the independent testing of ConsumerLab.Com (subscription fee is required).

Maryann Napoli, Center for Medical Consumers©

G’bye to low-fat diets

Is it just me? Or are we all hearing less and less about the importance of the low-fat diet? First, it was advised only for people who’ve had a heart attack. In time, the low-fat diet would be recommended for everyone, even children, as a good way to avoid heart disease. Eventually, there would be some serious back-peddling where it concerned babies and toddlers who, as it turns out, need lots of fat in their diets. Then there were those hard-to-explain population studies that show a lower incidence of stroke among people on high-fat diets. here’s one  Over the last decade—without any official retraction from the government or the cardiology organizations—there is less emphasis on the importance of the low-fat diet. It’s long overdue.

A new Cochrane review of all relevant clinical trials shows that the evidence supporting the low-fat diet is thin…and always has been. In fact, the reviewers found no good research to answer the most basic of questions: Are monounsaturated (e.g., olive oil, canola oil, nuts, avocados, etc) or polyunsaturated fats (plant foods and oils) healthier than saturated (animal) fats? The review acknowledges the negative, but unintended, consequences of telling the healthy public to reduce fat intake. It led many Americans to consume more carbohydrates, particularly starchy, sugary refined foods.

Ten years ago, the first Cochrane review of all low-fat diet/heart disease prevention studies was published in the British Medical Journal. Here is how the findings were expressed at the time:

“Despite decades of effort and many thousands of people randomized [into clinical trials], there is still only limited and inconclusive evidence of the effects of modification of total, saturated, monounsaturated, or polyunsaturated fats on cardiovascular morbidity and mortality.”

The existing research hasn’t improved much in the intervening ten years. The new Cochrane review, which is an updated version of the 2001 review, was published recently in the Cochrane Library (online subscription-only library). The Cochrane reviewers identified 48 studies with a combined total of 65,508 participants, including studies published in the last decade. No studies proved that people would live longer, avoid a stroke or heart attack, or showed anything else that might motivate people to alter the fat content of their diets.

As with all Cochrane reviews, the best studies are identified and results are combined. In this case, all the bad outcomes you might like to avoid—heart and vascular disease, cardiovascular death, heart attack, stroke, angina, and the need for heart surgery—-were also combined. Once that was done, an unimpressive 7% reduction in bad outcomes was noted among the study participants on a reduced fat diet, compared with those randomly assigned to continue their usual diet. Generally speaking, diet studies are difficult to conduct and costly. And they usually don’t last very long. Two years is the longest duration of any study in this review and it largely accounts for the aforementioned 7% reduction. Yet the Cochrane reviewers saw this small reduction as a good sign that some form of a low-fat diet might be shown to be heart healthy had the participants been followed several years longer.

This updated Cochrane review entitled, “Reduced or modified dietary fat for preventing cardiovascular disease,” was conducted by Lee Hooper, PhD, University of East Anglia in the U.K. and colleagues at other British universities. The review did not disprove the idea that the low-fat diet is best for the heart. Rather, it found no strong evidence to support this longstanding public health message, which no doubt led many healthy people with high cholesterol to take cholesterol-lowering statin drugs unnecessarily. (Ever since the early 1990s, healthy people with elevated blood cholesterol are usually told to go on a low-fat diet.  It has long been known that two out of three of them will fail to get it down to normal with a low-fat diet and exercise. Statins are the next step—see current ads for Lipitor.)

What’s the take-home message from this Cochrane review? Uncertainty is the short answer. Unfortunately, the low-fat message to the public was delivered with a certainty that never existed. It has probably made many people take all other nutrition advice with a grain of salt.

In the early days of dietary fat studies, researchers relied heavily on the less definitive form of research called population studies, aka observational studies.  The researchers observed that people in some countries with low dietary fat intake also had low rates of heart disease and came to the conclusion that the low-fat diet is the key to avoiding heart disease.  As time went on, researchers tried to tease out factors, other than fat intake, that could account for a country’s lower rate of heart disease, for example, red wine drinking in France.  The next step is the type of study used in medical treatment research—participants are  randomly assigned either to go on a low-fat diet or stay on their usual diet, for example, the aforementioned two-year study in the Cochrane review.

Where do we go from here? You can’t go wrong eating real food. If you’re not sure what that means, read Michael Pollan’s Food Rules. If you want to know more about how the low-fat diet became standard medical advice, read our 2008 review of  Good Calories, Bad Calories by Gary Taubes.

Maryann Napoli, Center for Medical Consumers©

Reducing salt intake has no effect on heart risk

Reducing the salt in your diet may lower your blood pressure a bit, but it will not reduce your chances of dying from heart disease or having a heart attack or stroke. That’s the conclusion of a new review of all relevant clinical trials conducted by the Cochrane Collaboration, an independent international organization that evaluates research. Another example of conventional medical wisdom found to have no supporting evidence. (Reminds me of statin drugs—so good at reducing cholesterol, but pitiful at cutting the risk of heart attack and stroke in people without heart disease. click here)

The Cochrane reviewers identified seven studies with a combined total of 6,489 participants. Three trials had participants with normal blood pressure (Note: definition of “normal” has changed over the years); two trials had participants with high blood pressure; one had a mix of people with normal and high blood pressure; and one trial with participants with congestive heart failure. Most of the trials followed the participants for seven months to three years. Only one trial followed its participants for more than 12 years.

The trials weren’t ideal in terms of detail provided and length of follow-up, according to the Cochrane reviewers, but they were the best of all existing research on the effects of salt restriction on blood pressure. All seven trials had randomly assigned participants to either salt reduction or not. One trial, however, was an exception in that it replaced sodium with a high potassium substitute. “Potassium has effects on blood pressure and may have deleterious effects in individuals with renal [kidney] disease,” wrote the Cochrane reviewers. Most of the trials did not attempt to change other aspects of the participants’ usual diet.

Here’s what happened to the participants who were told to reduce salt intake: Salt restriction reduced systolic and diastolic blood pressure by an average of 1 mmHg (millimeter of mercury) in people with normal blood pressure and by 2 to 4 mmHg (millimeters of mercury) in those with congestive heart failure.

In short, this Cochrane review found no proof that salt restriction will help you live longer or avoid a heart attack or stroke. And guess what? This isn’t news. Here’s my interview with hypertension researcher Michael Alderman, MD, saying virtually the same thing in 1992. And again in 2003 with this interview entitled, “Prehypertension—how real is this new “disease?”  It is, of course, possible that some time in the future a well-designed, long-term clinical trial might find a health benefit to reducing salt intake. In the meantime, the  salt-reduction choice is yours to make.

Maryann Napoli, Center for Medical Consumers(c)

How risky is diabetes 2?

There is, we are told, an “epidemic” of diabetes 2 in the U.S. Never mind that the definition of who has this condition was expanded in the 1990s, thus turning more than a million people into diabetics overnight. One of the worst things about diabetes 2 is its increased risk of potentially fatal heart problems. In time, however, research would show the drugs prescribed to cut the chance of this happening will themselves increase the risk of potentially fatal heart problems. Now a new study shows that people who receive a diabetes diagnosis after the age of 60 are not at same risk for heart problems as those diagnosed at younger ages.

Well, if you’re straining to find something positive in this bleak picture, as I am right now, this seems like something to cling to.

The new study, called the British Regional Heart Study, included only men—a problem right there for the other half of the population. The 4,045 men, age 60 to 79 years, were screened for diabetes 2 from 1978 to 1980 and asked to answer extensive questionnaires. The research team was led by Dr. S. Goya Wannamethee, University College, London, UK.

All were divided into four groups: Men who did not have diabetes or a heart attack; men with a prior heart attack but no diabetes; men with diabetes for more than 16 years and diagnosed before age 60 (early onset); and men with diabetes for at least 4 ½ years and diagnosed with diabetes after age 60 (late-onset).

Here’s what the British researchers found in the nine-year duration of their study: 9% of the men without diabetes or heart attack died from heart disease or suffered a major cardiovascular event (e.g., stroke, heart attack). Although a heightened chance of these “events” goes with a diabetes diagnosis at any age, the late-onset diabetics had a lower risk.

So how large is a man’s chance of suffering a cardiovascular complication of diabetes 2? The risk rises to 22% in the early-onset diabetes group and 16% in late-onset group. Put another way: 78%of the diabetics at either level of risk will not have a heart attack or premature death in the next nine years. The highest risk (26%) is for the men without diabetes who have suffered a heart attack. Are you ever old enough to stop thinking that diabetes will do you in prematurely? Yes, according to the editorial that accompanied this study. By the time a man hits age79, his risk of heart disease death is already high.

This is a small study that didn’t have enough participants to come to a firm conclusion—only 107 of the 4,045 men had early-onset diabetes. Still, the British researchers noted, earlier studies have also “suggested that the impact of diabetes on mortality decreases with increasing age at onset.”

In the editorial, Dr. Iskandar Idris, University of Sheffield, UK, cites a common, but evidence-free, treatment that is also based on the assumption that diabetes 2 confers the same level of heart disease risk to all. “Current cholesterol guidelines urge doctors to treat patients with diabetes to low LDL-cholesterol targets—less than 100 mg/dL—even though there is a lack for evidence to support this target.”

This study appeared in a recent issue of Archives of Internal Medicine as part of its ongoing “Less is More” series that illustrates “How Less Health Care Can Result in Better Health.”

More to think about

-In his book Overtreatment, H. Gilbert Welch, MD, describes how the definition of diabetes 2 changed since he was in medical school (1970s), “If you had a fasting blood sugar over 140, then you had diabetes. But in 1997 the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus redefined the disorder. Now if you have a fasting blood sugar over 126, you have diabetes. So everyone who has a blood sugar between 126 and 140 used to be normal but now has diabetes. That little change turned over 1.6 million people into patients.”

-Nortin Hadler, MD, believes what is now called diabetes 2 is largely a construct invented by the pharmaceutical industry. Read this 2009 interview. He is the author of Worried Sick. A prescription for health in an overtreated America, which has a section on diabetes 2.

-See this 2009 study showing which oral diabetes 2 drugs are riskier than others. Only generic and drug class names are used throughout this medical journal article.

Maryann Napoli, Center for Medical Consumers

Of wine, cholesterol, and triglycerides

For years I’ve wondered why doctors continue to test women for high cholesterol when studies show it has no value in predicting heart attack or stroke. And more to the point, why prescribe cholesterol-lowering drugs to women for heart disease prevention when there’s no proven benefit? Yes, men appear to benefit from cholesterol-lowering, but surprisingly few as it turns out. Wouldn’t it be better—and safer—to simply tell us to have a daily glass of wine? My questions only became magnified this week when I came across the Copenhagen Heart Study (CHS), which has followed healthy people for over 33 years to see who develops cardiovascular problems. As with the Framingham Heart Study, the CHS has generated multiple smaller studies over the years.

I stumbled across the CHS for the first time when its latest findings appeared this month in Annals of Neurology. It focussed on what is probably the most feared consequence of cardiovascular disease—an ischemic stroke. Keep in mind when you read the CHS results that—for men and women—high cholesterol has long been considered a major risk factor for stroke, along with smoking and hypertension.

The CHS found that the blood fats known as triglycerides are more relevant to stroke risk than cholesterol. It concluded that increasing levels of nonfasting triglyceride are predictive of a woman’s high risk for stroke, while increasing cholesterol levels are not. As for men, increasing levels of nonfasting triglyceride are associated with an increased risk of stroke, but cholesterol becomes a risk for stroke only when it’s extremely high (348 mg/dl or higher). These findings were confirmed by a 31-year Norwegian study published last year in the European Journal of Epidemiology.

The standard blood test almost always includes measurement of triglycerides. The new twist introduced by the Danish researchers is nonfasting triglycerides. Their explanation: “except for the first hours of the early morning, most individuals are in the nonfasting state most of the time.” Triglycerides are stored in our fat tissue among other places; the major stimulus for triglyceride production is not fat intake, but carbohydrates and sugar. While earlier research indicates that triglyceride might be a better predictor of stroke, the CHS is the first to separate results by gender. Before we all start to get carried away with triglycerides, keep in mind that there is no proof that lowering someone’s triglycerides also lowers the risk of stroke.

Now for the wine…and here’s another reason to stay with the Danish research. If stroke is the main thing you’d like to avoid (and it is mine), there’s much to be said for drinking. I’ve always been intrigued by the population (observational) studies that show that people who drink alcohol have a lower risk of stroke than people who don’t. Denmark became an unintentional experiment in 1976 when this nation of liquor and beer drinkers turned rather suddenly and enthusiastically to wine. The change was due to the opening of the European market.

Here’s what the researchers found after following 13,000 men and women, age 30-70 years, for the first 12 years after wine became instantly more accessible. “Low to moderate intake of wine is associated with lower mortality from cardiovascular and cerebrovascular disease [stroke] and other causes. Similar intake of spirits implied an increased risk, while beer drinking did not affect mortality.”

This off-shoot of the CHS is interesting from several perspectives. It’s the first to study the health effects of wine drinking in a non-Mediterranean country; it did not show that other forms of alcohol had similar health benefits to wine, as all other studies have since found; and it had a broader definition of “low to moderate drinking” than U.S researchers typically use.

Low wine consumption was defined as 1 to 3 glasses of wine daily, moderate was 3 to 5 glasses of wine daily. There was a 49% decrease in total mortality among the moderate drinkers and a 30% decrease among those with low consumption, compared with people who never drank wine. As for Denmark’s increase in wine consumption during the 12-year-study period, it went from 17% of total alcohol consumption in 1975 to 30% in 1992. The CHS was financed by the Danish National Board of Health.

It’s likely that the medical profession will soon let go of the idea that cholesterol is an important risk factor. And the unwarranted enthusiasm for statins will dim slowly as we get to the end of this year when the patent for Lipitor runs out. This $10 billion-a-year cholesterol-lowering statin drug, which is excellent at lowering cholesterol but modest (at best) at lowering the chance of stroke or heart attack, will be the last of the statin drugs to lose exclusive rights.

Raise a glass of wine to that thought.

For more information
-Not convinced that women with high cholesterol but no heart disease will not benefit from cholesterol-lowering drugs? Read this and be sure to click into the link to the 2004 JAMA study referenced within the article. As for the effectiveness of these drugs in men, click here And lastly click here to see the effectiveness of cholesterol-lowering drugs for people who already have heart disease.

-Triglycerides are more relevant to heart disease than cholesterol, according to extensive research dating back to the 1950s. For more on this topic, see Gary Taubes’s book, Good Calories, Bad Calories—Challenging the conventional wisdom on diet, weight control, and disease.” click here

-Here’s the 1995 Copenhagen Heart Study results about the 12-year period following the broad availability of wine. click here

-Need a more recent wrap-up of all the best wine-heart disease studies? Read this analysis of 21 such studies that confirmed the finding that light- to moderate-drinking is better for the heart than not drinking. As for stroke mortality, even just one drink a day will lower your chances. And by the way, binge drinking is a major no no. click here

-Too many white people in these drinking and stroke prevention studies? Here’s one with the same finding in favor of moderate drinking but the participants are broadly representative of the U.S. population (be sure to scroll way down).

Maryann Napoli, Center for Medical Consumers(c)

Drugs to prevent stroke and heart attack

It happened slowly over several decades and now millions of healthy Americans are taking drugs for the rest of their lives because they might have a heart attack, stroke, or hip fracture some time in the future. As recently as 25 years ago, for example, only people who already had a heart attack were told to lower their cholesterol with drugs; now high cholesterol (the definition keeps changing) must be reduced in everyone, even kids.

Drug treatment of risk factors like bone loss is firmly entrenched in the American psyche as prevention. More accurately, though, this type of drug treatment is just risk reduction, or lowering the chance of some dire occurrence like a hip fracture. Once told you’re at high risk for something, you are expected to take a drug to lower that risk and to comply with the followup doctor visits. You have, in effect, become a patient, albeit one without any symptoms. Rarely, does the prescribing physician explain the math to you. Simply put, what is the “patient’s” risk of having a heart attack now and how much of that risk is lowered by taking the drug. One thing that is almost always left out is an estimate of the drug-related adverse effects.

I thought of all this while trawling the Web for risk calculators that might fill in the missing information for people with uninformative doctors. The websites aren’t very good, but here’s a standout: www.thennt.com The website’s name refers to the number needed to treat (NNT), a statistical term researchers use to describe how many people must be given a drug or treatment to save one person from potentially fatal condition like a stroke. Another way of putting it: how many people will risk the side effects of treatment and derive no benefit. The calculations are based are based on results of clinical trials.

TheNNT.com was started in October by several New York doctors who want other doctors and the public to understand the size of the benefits and risks for drugs or other common medical treatments. Click here for the section about cholesterol-lowering statin drugs for people without heart disease. It’s blunt and to the point: “98% of the people who take statins saw no benefit” and “0.4% were helped by preventing a stroke”. Harms are also calculated: “0.6% were harmed by developing diabetes”. Click here if you want to see how marginally effective statins are even for people with heart disease.

The sources for each treatment’s calculation are described under “Where we get the numbers”. Usually it is a systematic review, most often a Cochrane review, and there are caveats, when appropriate. A caveat example: “Virtually all of the major statin studies were paid for and conducted by their respective pharmaceutical company. A long history of misrepresentation of data and occasionally fraudulent reporting of data suggests that these results are often much more optimistic than subsequent data produced by researchers and parties that do not have a financial stake in the results.”

You are not likely to find this level of honesty on other websites, especially those funded by the pharmaceutical industry. Typical is this widely used “risk assessment tool” from the National Cholesterol Education program. (This government agency made news in 2004 when its guidelines for who should be on cholesterol-lowering drug therapy were expanded. Eight of the nine experts who wrote the guidelines had financial ties to companies that make statin drugs.) Click here for what I would call a “Should I go on drugs” quiz with seven personal questions such as age, gender, and systolic blood pressure. This calculator estimates your risk of having a heart attack—and that’s about it. If, after answering the quiz, your risk comes up as 3%, for example, which is “3 of a 100 people with this level of risk will have a heart attack in the next ten years.” If you’re inclined to look on the bright side, just flip that statistic around to “97 out of 100 people like me” are not going to have a heart attack in ten years.

Then there’s the American Heart Association “blood pressure health risk calculator”. On the opening page Schering-Plough, maker of heart drugs, and Omron, maker of home blood pressure monitoring machines, are featured as the “proud sponsors” of this website. (Note to AHA: Thanks for being so upfront but try finding sponsors without such obvious conflicts of interest.) Could this proud sponsorship explain the fearmongering I found on this website? At the start of the quiz, it says that “women’s risk of heart disease starts to rise after menopause.” That’s a tad alarmist, considering that 78% of female deaths from heart disease in the U.S. occur after the age of 75. (I got this stat from the CDC last year but don’t expect to see it in any women and heart disease awareness campaigns.)

The AHA explains its risk calculator this way: “Your risk estimates are shown in comparison to a person your same age with normal blood pressure below 120/80.” It’s easy to see how this newly lowered threshold for normal will lead doctors to prescribe inappropriate drug treatment, especially if they are unaware of this Cochrane review that found no benefit to reducing blood pressure below 140/90. Yes, the new definition of “normal” has recently become “below 120/80”. I guess we can’t expect a pharmaceutical industry-funded website to warn about the futility of taking drugs to bring blood pressure below 140/90 just because studies show this will not prolong life or reduce the chances of having a heart attack, stroke, or kidney failure.

The AHA and the National Cholesterol Education Program provide the calculations for hypertension and cholesterol that are most likely to influence physicians. Let’s hope that more of them make their way to www.thennt.com

Maryann Napoli, Center for Medical Consumers©

Statins don’t work for people w/o heart disease

 

Attention all people who take cholesterol-lowering statin drugs! Pay particular attention if you’re taking the drug because your cholesterol level is high, but you don’t have heart disease. If this description fits (and it does most statin-takers), then you may know that taking a statin every day for five years provides about a 1% reduction in your chance of having a heart attack or dying of a heart attack.

This benefit established long ago was confirmed in a new meta-analysis of 12 statin vs. placebo trials that also reported serious adverse events and deaths from all causes. How else can researchers tell whether the drug itself is killing some people? How else would you, the statin-taker, know whether the chance of suffering a severe side effect is greater than the chance of avoiding a heart attack?

Apparently, statins don’t cut your chance of dying from anything. “There’s no lifesaving benefit to statins for people without heart disease when you look at deaths from all causes in the less biased trials,” said Jim M. Wright, MD, PhD. University of British Columbia, Vancouver, the lead author of the new analysis. “The number of people who died in the placebo group was the same as the number of people who died in the statin group.”

Yes, the drugs are terrific at lowering cholesterol, as anyone on a statin will readily tell you, but pitiful where it concerns the ultimate goal of avoiding a heart attack.

Ever since statins were marketed for healthy people with high cholesterol, the prevailing message from drug companies and doctors has been “these drugs are extremely safe.” Over the years, muscle pain has been acknowledged as more common than previously thought. The Mayo Clinic website typifies the current thinking:

“The most common statin side effect is muscle pain. You may feel this pain as a soreness, tiredness or weakness in your muscles. The pain can be a mild discomfort, or it can be severe enough to make your daily activities difficult. For example, you might find climbing stairs or walking to be uncomfortable or tiring.

Very rarely, statins can cause life-threatening muscle damage called rhabdomyolysis (about one case for every 15 million prescriptions).”

Dr. Wright and colleagues looked beyond muscle damage for the full range of serious adverse events (SAEs) experienced by the participants in the 12 trials included in their analysis. The SAEs include such disparate events as pneumonia, hospitalizations, and having to undergo a coronary-artery-opening procedure. The chance of having a SAE (about 30%) is exactly the same whether you take a statin or placebo,” said Dr. Wright. “This suggests that statins must be increasing some SAEs that counterbalance the reduction in heart attacks.”

Why, I wonder, do we hear that muscle problems are the only SAEs of statins? “All but one of these statin trials were funded by companies that make statin drugs,” answered Dr. Wright. “In the safety data it appears the authors were only looking for muscle damage. When they didn’t find much, they concluded the drugs are really safe.”

I once cured a case of Alzheimer’s disease simply by telling a friend that her 85-year-old mother could be suffering adverse effects from the statin she was on for years. With much difficulty, my friend finally got her mother’s doctor to stop the statin. The mother’s cognitive impairment disappeared, so did the Alzheimer’s diagnosis. Anecdotal, I know, but nonetheless interesting. Problems with memory, thinking and concentration are among the common adverse effects reported by statin users to an ongoing survey at the University of California, San Diego (click here).

At the risk of making your eyes glaze over, here’s something you should know about the clinical trials supporting statin use in healthy people. Even when the reviews are limited to the 12 best trials, there remains the potential for serious bias in favor of statins. Here’s just one example provided by Dr. Wright. In an ideal trial, both study participants and their doctors should not know who is taking the real drug and who is on placebo. However, statins can dramatically reduce cholesterol levels. The dramatic drop in cholesterol in people randomly assigned to take statins serves to tip off doctors as to who is on the active drug as opposed to the placebo.

When the doctors know who is on the statin drug, explained Dr. Wright, it can affect their decisions about who will be referred for a coronary artery-opening procedure, known as revascularization. “A doctor might be inclined to refer a patient for revascularization, but decide against it once he or she sees that the patient’s cholesterol level is very good.” The number of revascularizations is one “outcome” that most statin trials use as a measure of the drug’s effectiveness.

Maryann Napoli, Center for Medical Consumers©

Dr. Wright reports no conflicts of interest regarding cholesterol-lowering drugs. This analysis was published in the Therapeutics Initiative Letter, an online newsletter of the University of British Columbia (click here). Dr. Wright is the editor-in-chief of this publication, a practising physician specialist in clinical pharmacology and internal medicine, and a professor in the Department of Anesthesia, Pharmacology, & Therapeutics, UBC.

Check out this new website for weighing the harms and benefits of statins for primary prevention. Added December 7, 2010.