Prescribing information for clopidogrel (Plavix) will now include a boxed warning that the drug can be less effective in poor metabolizers, the FDA indicated.
The new warning suggests that many if not all patients on clopidogrel should undergo genetic testing to determine whether they have variants of the CYP2C19 gene associated with poor metabolism of the antiplatelet drug.
Clopidogrel is actually a prodrug that requires metabolic activation by the CYP2C19 enzyme to become effective. Poor metabolizers get little or no benefit from the drug at standard doses, and therefore are at increased risk for thrombotic events and death, the FDA said.
The drug’s label has carried a similar warning since May 2009, but the FDA said today that “it was important to highlight this risk in a boxed warning” in light of a subsequent review of data.
Seven different variants of the CYP2C19 gene are associated with poor metabolism of clopidogrel. According to the FDA, patients with two loss-of-function alleles, which do not have to be identical, will be poor metabolizers.
The agency estimated that 2% to 14% of patients are poor metabolizers, with some racial-ethnic groups more likely to be affected than others. Whites have the lowest prevalence of poor metabolism and Asians have the highest.
New methods needed to ID cardiac catheterization candidates
It’s time to re-think how patients are selected for cardiac catheterization, say doctors at Duke University Medical Center, after reporting in a new study that the invasive procedure found no significant coronary artery disease in nearly 60 percent of chest pain patients with no prior heart disease. “Our data show that up to two thirds of the patients undergoing invasive cardiac catheterization are found not have significant obstructive disease,” says Manesh Patel, MD, a cardiologist with the Duke Heart Center. He’s the lead author of the study published in the March 11 issue of the New England Journal of Medicine.
“We’re spending a lot of energy and money to evaluate chest pain which often leads to cardiac catheterization, which, we now know, often finds that patients don’t have significant obstructive disease,” Patel says. “Our research shows that our methods for identifying patients at risk for obstructive disease need significant improvement.”
ScienceDaily (Mar. 11, 2010) — People whose “bad” cholesterol and risk of future heart disease stay too high despite cholesterol-lowering statin therapy can safely lower it by adding a drug that mimics the action of thyroid hormone. In a report published in the Mar. 11, issue of the New England Journal of Medicine, Johns Hopkins and Swedish researchers say an experimental drug called eprotirome lowered cholesterol up to 32 percent in those already on statins, an effect equal to that expected from doubling the statin drug doses, without harmful side effects.
The researchers caution that the results don’t suggest that eprotirome will or should replace statins, which are the current gold standard for treating high LDL cholesterol. However, the results of their small trial on 168 patients do suggest that eprotirome may eventually be a promising addition to statin therapy, a substitute for statins in people who can’t tolerate their side effects, or a novel treatment for mixed dyslipidemia, a condition in which people have high levels of lipids other than cholesterol such as triglycerides or apolipoprotein B (apo B).
Coffee Associated With Reduced Risk of Hospitalization for Heart Rhythm Disturbances
ScienceDaily (Mar. 3, 2010) — Coffee drinkers may be less likely to be hospitalized for heart rhythm disturbances, according to a new study by the Kaiser Permanente Division of Research in Oakland, Calif. The researchers, who note the findings may be surprising because patients frequently report palpitations after drinking coffee, are presenting the study at the American Heart Association’s 50th Annual Conference on Cardiovascular Disease Epidemiology and Prevention in San Francisco on March 5, 2010.
While it has been established that very large doses of caffeine, the most active ingredient in coffee, can produce rhythm disturbances, there has been limited epidemiologic research about the caffeine doses people take. Previous data from a population study in Denmark compared heavy to light coffee drinkers with respect to risk of atrial fibrillation, the most common major rhythm disturbance, and found no statistically significant difference. This research presentation is believed to be the first large, multiethnic population study to look at all major types of heart rhythm disturbance, the researchers said.
The researchers followed 130,054 men and women and found that those who reported drinking four or more cups of coffee each day had an 18 percent lower risk of hospitalization for heart rhythm disturbances. Those who reported drinking one to three cups each day had a 7 percent reduction in risk, according to Arthur Klatsky, MD, the study’s lead investigator and a senior consultant in cardiology at Kaiser Permanente Division of Research in Oakland, Calif.
Transcendental Meditation has been around for many years and is perhaps the most scientifically tested of all forms of meditation. Two studies presented this week add to the evidence that this form of stress reduction benefits people with heart disease and those at high risk for it. One study, presented on Monday at the American Heart Association annual meeting, found that heart disease patients who practice TM have almost 50% lower rates of heart attacks, stroke and deaths compared to similar patients who don’t practice meditation. The study was funded with a $3.8-million grant from the federal government and was conducted at the Medical College of Wisconsin in collaboration with the Institute for Natural Medicine and Prevention at Maharishi University of Management in Fairfield, Iowa, a major center of TM research.
L.A. Times; November 8, 2009
New Method to Grow Arteries Could Lead to ‘Biological Bypass’ for Heart Disease
ScienceDaily (Mar. 9, 2010) — A new method of growing arteries could lead to a “biological bypass” — or a non-invasive way to treat coronary artery disease, Yale School of Medicine researchers report with their colleagues in the April issue of Journal of Clinical Investigation.
Coronary arteries can become blocked with plaque, leading to a decrease in the supply of blood and oxygen to the heart. Over time this blockage can lead to debilitating chest pain or heart attack. Severe blockages in multiple major vessels may require coronary artery bypass graft surgery, a major invasive surgery.
“Successfully growing new arteries could provide a biological option for patients facing bypass surgery,” said lead author of the study Michael Simons, M.D., chief of the Section of Cardiology at Yale School of Medicine.