Vytorin trial shows little or no benefit against heart disease [Updated]

For the second time in as many years, a large clinical trial has found that the key ingredient in the heavily advertised drug Vytorin provides little or no benefit in preventing heart disease compared to a competing product. The ingredient is ezetemibe, which blocks the absorption of cholesterol in the intestines. It is sold alone under the brand name Zetia or in combination with the cholesterol-lowering drug simvastatin under the brand name Vytorin. The combination of drugs has been shown to reduce cholesterol more than simvastatin alone, but that apparently does not translate into a lower risk of heart disease.

In the original trial, reported last year in January, Vytorin was compared with generic simvastatin in a group of 720 patients with a genetic disorder called heterozygous familial hypercholesterolemia, in which unusually high levels of low-density lipoproteins, commonly known as LDL or "bad" cholesterol, accumulate in the blood, increasing the risk of cardiovascular disease. Vytorin reduced the level of LDL in the blood of the patients by 58%, compared with a 41% reduction produced by simvastatin, which blocks production of cholesterol in the liver. But to determine how the drugs affected the risk of heart disease, researchers looked at the thickness of plaque in the carotid and other arteries. Thicker plaque increases the risk of plaque breaking off and producing clots that lead to heart attacks. The researchers found that plaque actually grew slightly more in the patients taking Vytorin than it did in those taking only simvastatin. Since then, prescriptions for Zetia have fallen from nearly 16.5 million in 2007 to less than 13 million in 2008, while those for Vytorin fell from 22 million to 16.5 million. The new results could lead to further declines.

A new study to be reported Monday at the American Heart Assn. meeting in Orlando, Fla., and published online in the New England Journal of Medicine compared ezetemibe to Niaspan, a controlled-release version of the B vitamin niacin. Niacin is known to raise levels of high-density lipoprotein, commonly known as HDL or "good" cholesterol. Many people have problems taking niacin, however, because it causes flushing. It is thought that Niaspan, because of its slow release, is less likely to produce this side effect.

Dr. Allen Taylor, who was at the Walter Reed Army Medical Center in Bethesda, Md., when the study began, and his colleagues enrolled 363 people with heart disease or at a high risk of developing it and who had been taking statins for an average of six years. About half were given Zetia in addition to their statins and the rest Niaspan. The study was terminated early in July, about four months early, when investigators concluded there was a clear difference between the two groups -- although they did not say which was better at the time.

Taylor reported at a news conference Sunday that Niaspan shrank plaque in carotid arteries by about 2%, while Ezetemibe had no effect, even though it reduced cholesterol. There were two heart attacks or heart-related deaths in the 160 people given Niaspan, but nine among the 165 given Zetia. About a third of those who received Niaspan did suffer flushing, however.

Zetia "should be better for the arteries and it wasn't," Taylor said at the news conference. "The drug wasn't operating as you would otherwise expect it to."

But Peter Kim, director of research at Merck & Co., which markets Vytorin along with Schering-Plough Corp., said the study was too small to draw any firm conclusions from it. He said the drug is now in other trials involving about 25,000 people and that physicians should wait for results from them before deciding not to prescribe the drug.

In an editorial accompanying the paper in the New England Journal, researchers from Johns Hopkins University agreed with him. "Although the study results are provocative, I am not convinced," said Dr. Roger S. Blumenthal, a cardiologist, who argued that the study was too small and too short. "These early results offer no conclusive evidence that niacin along with a statin will actually lower the number of deaths and incidents of heart attack from coronary artery disease down the road."

Until those results are available, however, consumers might find that a combination of a generic statin and over-the-counter niacin might be more cost effective. While Vytorin and Niaspan each cost about $3 to $4 per day, niacin can be had for a few pennies and generic simvastatin costs less than 40% of the price of  Vytorin.

— Thomas H. Maugh II

[Updated, 7:30 p.m.: According to Merck, Zetia costs $3.23 a day, and the amount of Niaspan used in the study costs $7.48 a day.]

NIH terminates emergency resuscitation trials for cardiac arrest

The National Institutes of Health has prematurely terminated a clinical trial testing two techniques designed to improve survival when paramedics treat heart attack victims, concluding that neither one provided any benefit. One trial tested how much CPR paramedics should perform before determining whether the patient needed to be defibrillated (shocked) to restart his or her heart. The second tested the efficacy of a device called an impedance threshold device or ITD that had been shown in animal trials to increase blood flow to the heart during CPR. About 11,500 patients already had been treated during the trial, and the researchers concluded that enrolling more would not change the results.

CPR performed by paramedics is a combination of chest compressions (to pump blood through the body) and rescue breathing. Lay people are encouraged to use only chest compressions until paramedics arrive.

Paramedics treat about 350,000 people with cardiac arrest, in which the heart stops beating, in the United States each year, but fewer than 10% of patients survive. In the majority of cases, the patient's heart had simply stopped beating for too long before paramedics were summoned and arrived. But health officials had hoped the new techniques could provide some improvement in survival rates.

In one arm of the trial, paramedics performed CPR for only 30 to 90 seconds before checking to determine whether defibrillation was indicated. In the other arm, they performed it for at least three minutes before checking. Small trials have given different results, with some showing that a short delay is better and others showing the long delay is preferable. But the new trial's Data and Safety Monitoring Board concluded that neither was more effective than the other. "Both techniques appear to be equally beneficial," said Dr. Ian Stiell of the Ottawa Hospital Research Institute in Canda, the principal investigator.

The ITD is a small hard-plastic device, about the size of a fist, that is attached to the face mask or breathing tube during CPR. It is designed to improve circulation by enhancing changes in pressure within the chest during CPR. In animal studies and small studies in humans, the device was found to markedly increase blood flow to the heart and raise blood pressure. Researchers had hoped that would improve retention of neurological function in patients who survived. Some patients whose heart stops for prolonged periods have severe neurological impairment that interferes with their quality of life.

In the trial, patients were randomized to receive either the ITD or a nonfunctional device that looked the same. Researchers found that survival was the same in both groups, as was retention of neurological function, suggesting that standard CPR was as effective as CPR with the device.

Patients in both arms of the trial will be studied for another six months to determine if there are any long-term effects.

-- Thomas H. Maugh II

Photo: An instructor teaches CPR. Credit: Los Angeles Times

Pumps are better for heart bypass surgery

Sometimes the old ways are better.

Historically, surgeons performing coronary artery bypass graft, commonly known as CABG (pronounced cabbage), for blocked arteries would stop the heart, using a heart-lung bypass machine to keep the patient alive during the procedure. In recent years, however, who's known as the beating-heart procedure, in which the heart is allowed to continue working, has become more popular. Cardiologists assumed that using the heart-lung machine increased the risk of stroke and of mental impairment after the surgery. Turns out that, in most cases, those concerns were misplaced and the machine is better.

CABG, in which a healthy vein is removed from a leg or elsewhere and used to bypass a blocked coronary artery, is the most common surgical procedure in the world. An estimated 253,000 Americans undergo the procedure each year at a cost upwards of $30,000 -- although beating-heart surgery is generally about 25% cheaper, another argument in its favor. (Another 1 million or more undergo balloon angioplasty in which a catheter is inserted through a vein in the groin and an inflatable balloon is used to compress the blockage, allowing blood to flow again.)

A team led by Dr. Frederick Grover of the University of Colorado School of Medicine in Denver studied 2,203 patients at 18 Veterans Affairs Medical Centers who needed bypass surgery. They were randomly selected to receive either the conventional technique or the beating-heart procedure.

The team reported today in the New England Journal of Medicine that initial results of the two procedures were comparable. At one month, no differences were observed in deaths or other complications following the surgery. But a year later, the story was different. About 2.7% of those receiving beating-heart surgery had died, compared with only 1.3% of those hooked up to the heart-lung machine. Overall, when deaths, strokes, heart attacks or the need for another bypass were included, problems were observed in 10% of those who received beating-surgery surgery compared to 7% of those on the machine. Some of the patients were given mental acuity tests before and after the procedures, and no differences were observed between the two types of surgery.

There were limitations to the study. All of the patients were male and younger and healthier overall than typical bypass patients. Some studies have suggested that the beating-heart procedure is better for women, the elderly and those with other illnesses. That possibility will have to be addressed in other studies.

Grover said he suspects many surgeons who prefer the beating-heart procedure will keep right on doing it. But for himself, he said he would be more conservative in deciding which patients should receive it.

-- Thomas H. Maugh II

Photo: Dr. Kathy E. Migliato, the first female heart surgeon at Cedars-Sinai Medical Center, completes a triple bypass. Credit: Carolyn Cole / Los Angeles Times

Heart attack rates up in women

Rates of heart attacks, as well as risk factors for cardiovascular disease, have dropped in middle-aged men over the last 20 years while women’s rates and risk factors have increased, according to a study published Monday. The research suggests that risk factors for heart disease, such as high blood pressure and high cholesterol, are not assessed or treated as aggressively in women as they are in men.

The study, published in the Archives of Internal Medicine, examined data from national surveys taken from 1988 to 1994 and a second time period, from 1999 to 2004. More than 4,000 men and women age 35 to 54, completed the surveys. Researchers looked at how often men and women had heart attacks and compared their scores on a tool that measures the risk of having a cardiovascular event over 10 years. The measurement, called the Framingham coronary risk score, takes into account age, cholesterol levels, blood pressure and smoking history.

In both time periods, men had more heart attacks than women. But the rates in men improved from 2.5% in the first time frame to 2.2% in the second time frame while women’s rates increased from 0.7% to 1%.

Men’s cardiovascular risk factors improved or remained stable over the two study periods while the only risk factor that improved among women was high-density lipoprotein levels. Diabetes prevalence increased among men and women, most likely due to the obesity epidemic, the authors said.

Traditionally, women have been thought to be largely protected from heart attacks and stroke before menopause due to hormonal influences, said the lead author of the study, Dr. Amytis Towfighi, an assistant professor of neurology at USC. But heart attacks and strokes are increasing in middle-aged women.

“People didn’t think that women in that age group were at high risk for heart disease and stroke,” she said. “But I suspect that with growing rates of obesity, women aren’t as protected as much as they have been in the past.”

The news isn’t all bleak for women, however. A second study in the same journal found that in-hospital survival rates after a heart attack have improved more for women than men.

-- Shari Roan

Photo: A woman undergoes an ultrasound test to look for atherosclerosis. Credit: Karen Tapia  /  Los Angeles Times

Rodent of the Week: How to mend a broken heart

The promise of stem-cell therapy is that researchers might be able to grow cells into specific tissue or organs that can replace or repair damaged parts. Researchers at Duke reported progress this week in developing a tissue patch that can be used for heart disease.

The scientists used mouse embryonic stem cells to grow a three-dimensional patch made up of heart muscle cells called cardiomyocytes. The tissue was able to contract and to conduct electrical impulses -- just like a real, beating heart. The patch, which looks like a piece of Chex cereal, was grown in biological substances, such as the blood-clotting protein fibrin and helper cells known as cardiac fibroblasts. These substances were crucial in coaxing the cells to grow in an organized manner that allowed them to function.

"When we tested the patch, we found that because the cells aligned themselves in the same direction, they were able to contract like native cells," a coauthor of the study, Brian Liau, said in a news release. "They were also able to carry the electrical signals that make cardiomyocytes function in a coordinated fashion."

More research is needed before heart patches could be used for humans with cardiovascular disease, Liau said. One of the major challenges is establishing a blood vessel supply to sustain the patch. The researchers will also test their model using non-embryonic stem cells. That could speed up the growth of the tissue since a human heart requires nine months for complete development. Moreover, if they could use a patient's own cells, it might prevent an immune system reaction.

The study was presented at the Biomedical Engineering Society annual meeting in Pittsburgh.

-- Shari Roan

Photo courtesy of Advanced Cell Technology Inc.

Smoking bans cut heart attacks for nonsmokers

Bans on smoking in public places and workplaces can sharply reduce the number of heart attacks among both smokers and nonsmokers, according to a new report issued today by the prestigious Institute of Medicine. The report provides strong support for the anti-smoking laws that are now in place in 21 states and the District of Columbia and is likely to bolster efforts to pass such laws elsewhere.

"It's clear that smoking bans work," said Dr. Lynn R. Goldman of the Johns Hopkins Bloomberg School of Public Health, who chaired the panel that produced the report. "Bans reduce the risk of heart attacks in nonsmokers as well as smokers."

"There's no question that secondhand smoke has an adverse health impact in workplaces and public environments," added Dr. Clyde Yancy, president of the American Heart Assn. "We must continue to enact comprehensive smoke-free laws across the country to save lives and reduce the number of new smokers."

Nearly 440,000 Americans die each year from smoking-related illnesses, more than a third of them heart disease, according to the heart association. About 38,000 of those deaths are related to secondhand smoke, which has many characteristics of other types of air pollution -- which has also been linked to heart disease. The association between illness and secondhand smoke was reinforced by the 2006 Surgeon General report on the consequences of exposure to environmental smoke.

But bans on smoking have remained controversial, in part because of fears that they would reduce traffic in bars and restaurants. Last year, the Centers for Disease Control and Prevention commissioned the Institute of Medicine to study the evidence. Some of the members of the panel were initially skeptical about the benefits of such bans, according to statistician Stephen E. Fienberg of Carnegie Mellon University in Pittsburgh, but they quickly changed their minds when they began reviewing the evidence.

The panel examined 11 studies of heart attacks in areas where bans were implemented and found a decrease in heart attacks in every study, ranging from a low of 6% to a high of 47%, depending on how the study was conducted. "Such consistent data confirms for the committee that smoking bans do, in fact, decrease the rate of heart attacks," they wrote. One study, for example, found that hospitalizations for heart attacks in Pueblo, Colo., dropped 41% in the three years after the city banned smoking in the workplace. In most of the studies, it was difficult to isolate the benefits for nonsmokers from those for smokers, but two of the studies showed a very clear benefit for nonsmokers.

The committee also surveyed the evidence from laboratory studies in animals and concluded that these results too supported bans. The studies show that particulates and other toxins in cigarette smoke can trigger heart attacks in people who have heart disease and may not know it, providing the final shove that pushes them into cardiac arrest.

-- Thomas H. Maugh II

Credit: John MacDougall / AFP/Getty Images

Experts propose a name change for women's heart disease

Heart disease in men is not the same as heart disease in women, say an influential group of cardiologists. Instead of referring to all heart disease by the medical terms of coronary artery disease or coronary heart disease, they argue that the term ischemic heart disease should be used to describe the illness experienced by women.

The paper, published today in the Journal of the American College of Cardiology, points out that the current focus of treatment for heart disease centers on obstructive coronary artery disease, which is when the arteries of the heart become clogged with plaque. However, women have less obstructive disease but higher rates of ischemia, which is defined as the inadequate flow of blood through the body because of constriction or blockage in blood vessels. Women with heart disease have more microvascular dysfunction -- affecting the small blood vessels of the body - compared with men.

Women tend to experience worse outcomes compared with men because the focus is on obstructive heart disease, the authors say, noting women have higher rates of sudden cardiac death before arriving at a hospital compared with men.

A name change may help doctors tailor diagnostic tests and treatments to better suit their patients, both men and women.

"Ischemic heart disease in women presents a unique and difficult challenge for clinicians due to a greater symptom burden, functional disability, greater healthcare needs, and more adverse outcomes as compared to men despite a lower prevalence and severity of anatomical coronary artery disease," they wrote. The authors represent the Women's Ischemia Syndrome Evaluation, a study group that includes Dr. C. Noel Bairey Merz, director of the Women's Heart Center at the Cedars-Sinai Heart Institute.

-- Shari Roan

Photo credit: Los Angeles Times

Heart-healthy fish consumption: Is the big one getting away?

For even the most skeptical consumer of news on health and nutrition, the link between increased consumption of fish and better heart health seemed to be something one could take to the bank--a reliable, unassailable finding.

No more. A major European study that tracked the health and habits of every older adult in a suburb of Rotterdam, the Netherlands, has found no significant relationship between their consumption of fish and their likelihood of developing heart failure. The latest Rotterdam study is published in the October issue of the European Journal of Heart Failure.

By the time a person reaches 40, he or she has roughly a one-in-four likelihood of suffering heart failure, and an estimated 5.7 million Americans live with the condition. Strong evidence exists that the regular consumption of even small amounts of the long-chain n-3 polyunsaturated fatty acids (also known as "Omega-3s") lowers an individual's risk of coronary heart disease. The American College of Cardiology recently published a review of four studies of Omega-3 intake and concluded there is "great promise" for the prevention of cardiovascular disease in the consumption of long-chain n-3 polyunsaturated fatty acids. 

Omega 3 consumption is thought to affect cardiovascular risk by suppressing inflammation, reducing heart rate, blood pressure and the buildup of fatty deposits in the blood, as well as by helping to maintain normal heart rhythm. But the current study suggests that the heart muscle's failure to pump sufficient blood for everyday activities is not averted by Omega-3 consumption.

The study divided its 5,299 subjects, with a mean age of 67.5 years, into five groups depending on the frequency and amount of their fish consumption. At the end of 11.4 years, the 669 subjects who developed heart failure were no more nor less likely to eat fish than those who did not, even after researchers took account of other lifestyle and dietary habits that might contribute to heart problems.

Dr. Marianne Geleinjse of Wageningen University in the Netherlands, one of the study's authors, acknowledged the study appears to run counter to mounting evidence for fish consumption's beneficial effects. "Based on our data, we would not change... advice" suggesting that people eat at least two weekly servings of fish, she added. Geleinjse cautioned that Dutch intake of fish is extremely low--on average less than one serving per week. "So maybe higher intakes are needed for any protection against heart failure," she noted.

-- Melissa Healy

At-home blood-pressure checks might help, but you need advice too

Most people with high blood pressure don't have the condition under control, increasing their risk of heart attack, stroke and kidney failure. So researchers at Duke University explored whether some low-key, at-home measures can make a difference.

The study (full version available), published online today in the Annals of Internal Medicine, is summed up in this way:

"In this trial, 636 patients with hypertension were randomly assigned to receive usual care; a telephone-delivered, nurse-administered behavioral self-management intervention; home blood pressure self-monitoring; or both of the latter two interventions. Compared with usual care, the adjusted improvement in the proportion of patients with blood pressure control at 24 months was 4.3% for the behavioral intervention group, 7.6% for the blood pressure monitoring group, and 11.0% for the combined intervention group."

In short, the combined approach of at-home checks and regular chats with a nurse was moderately effective; the single-tactic approaches weren't especially.

The researchers quite fairly point out that it's difficult to draw broad generalizations from the study, saying many participants did, in fact, have their blood pressure under control at the beginning of the study. And, too, the work was done through an academic health center, which couldn't be the case for everyone.

Nevertheless, the results back up earlier research suggesting that home interventions have some promise -- and that the costs are minimal. These days, that's no small thing.

For an earlier Los Angeles Times story about monitoring blood pressure at home, "Tracking a silent killer," click here.

Plus, tips from FamilyDoctor.org on how to do this properly.

And more on high blood pressure from eMedicineHealth -- causes, symptoms, treatment. ...

-- Tami Dennis

Photo credit: Los Angeles Times

Stiff back and legs = stiff arteries, study says

Want to know whether your arteries have begun to stiffen, putting you at greater risk of developing cardiovascular disease? Bend over.

Sit down against a wall, with your legs on the floor in front of you, that is, and try to touch your toes. In fact, reach beyond them if your yoga, Pilates or daily stretching routine make it possible.

For people over 40 -- even if they're a little overweight -- a new study shows that trunk flexibility may be a good indicator of arterial flexibility. Conversely, the study found, stiffness at the midsection seems to reflect arteries that have begun to lose their elasticity as well.

Elastic blood vessels help moderate blood pressure. Not surprisingly, then, researchers found that those who could not reach to or beyond their toes in the sit-and-stretch test were more likely than their flexible peers to have higher systolic blood pressure -- the peak pressure reading taken as the heart contracts). While midsection stiffness predicted arterial stiffness, the Japanese researchers found that subjects' muscle strength and cardio-respiratory fitness, as measured by their performance on an stationary bicycle, did not yield any clues to the shape their blood vessels were in.

The study, published today in the American Journal of Physiology, helps unpack the ingredients that make for a heart-healthy person. While regular exercisers have generally been found to have lower rates of cardiovascular disease, researchers have been in the dark about what part of regular exercise contributes most to that affect.

The Japanese study suggests that the key may be the flexibility that's a frequent side benefit of regular exercise. That's suggested by another recent study, which found that middle-age and older adults who undertook a stretching-exercise regimen significantly improved the flexibility of their carotid artery, which carries oxygen-rich blood to the brain (and which, when blocked, is the cause of an ischemic stroke).

So strike that yoga pose, strengthen your core and stretch your body, say the researchers: it may hold age-related arterial stiffening -- and cardiovascular disease -- at bay. "We believe that flexibility exercise ... should be integrated as a new recommendation into the known cardiovascular benefits of regular exercise," Kenta Yamamoto, a study author from Japan's National Institute of Health and Nutrition and the University of North Texas, said in a press release.

Need some help with those stretching exercises? Here are some tips from the American Heart Assn.

--Melissa Healy