News from the American College of Cardiology meeting (Part I)March 7-10, 2004New Orleans, Louisiana

Study Challenges Cholesterol Recommendations New research shows high levels of statins given to people who have just been hospitalized with heart attacks or high-risk unstable angina not only prevented future events but also saved lives. These findings call into question current guidelines on how low low-density lipoprotein (LDL) levels should be. This will have a major impact in the real world, says Dr. Eric Topol, chairman of the department of cardiovascular medicine at the Cleveland Clinic Foundation. It was striking how fast it was. It was a whopping benefit and unexpected. This changes everything. Data was presented at a meeting of the American College of Cardiology in New Orleans. Topol notes that in the management of atherosclerotic vascular disease, statin drugs have already surpassed all other classes of medicine in reducing the incidence of the major adverse outcomes of death, heart attack and stroke . In earlier trials, statins were able to reduce LDL cholesterol levels by 25 percent to 35 percent. The basis of our study was that statins were tested and were very, very effective, says Dr. Christopher P. Cannon, a cardiologist at Brigham and Women’s Hospital in Boston. But the drugs had not yet been tested in a hospital setting in people who were seriously ill. The current research set out to answer two questions, Cannon says. The first was whether statins would be effective in heart attack patients in a hospital setting. The second and bigger question was whether it would be worth it to lower cholesterol levels by 50 percent, instead of the 25 percent already demonstrated. Current guidelines from the National Cholesterol Education Program recommend that LDL cholesterol levels be less than 100 milligrams per deciliter of blood for patients with established coronary artery disease or diabetes. These researchers wanted to know if even lower was even better. The answer to both questions, it turned out, was yes. The trial involved 4,162 patients at 349 sites in eight countries. All of the participants had been hospitalized within the past 10 days with either a heart attack or high-risk, unstable angina. One group was given 40 milligrams of pravastatin each day (the standard therapy), while the other was given 80 milligrams of atorvastatin each day (intensive therapy). In the standard therapy group, the mean LDL cholesterol level attained was 95 mg per deciliter. In the intensive group, it went down to 62 mg per deciliter. These differing levels corresponded to different outcomes. Over a period of about 24 months, the intensive therapy group (atorvastatin) showed a 16 percent lower risk of overall major cardiovascular events and a 28 percent reduction in death. Every outcome measured was better in the intensive group, except for stroke, which was about the same in both groups. Even though the groups were followed for about two years, the benefit was seen extremely quickly, in less than 30 days. The surprising results suggest that ideal LDL cholesterol level should be quite a bit lower than currently recommended. The control group was getting gold-standard excellent care but this still added benefit, Cannon says. One surprising thing was how quickly it happened. The downside of this more intensive treatment is minimal, Cannon adds. We have to be a little cautious on the liver, he says. About 1 percent of the control group and 3 percent of the intensive therapy group experienced liver problems. In the real world, it will probably be higher. Which brings doctors to the next question: How easily and quickly will these results be translated into the real world? Hopefully the very clear results will mean that people going home from the hospital will get this treatment, Cannon says. But even today, as the editorial points out, only about 11 million people are getting statins when an estimated 36 million should be on them. Worldwide, more than 200 million people meet the criteria for treatment with statins while only 25 million are actually taking the drugs. This is largely a cost issue, Topol states. He points out that in Cleveland, the cost of 10 mg of atorvastatin per day (the recommended starting dose) is $900 per year, while the 80-mg dose costs $1,400 per year. At a collective $12.5 billion, statins are the largest prescription drug expenditure in the United States, he writes. It’s going to take a while to assimilate, Topol says. There’s a cost issue. That is why people don’t take statins today. Following Rules Helps After Heart Attacks Despite huge improvements in heart care over the past two decades, the flow of these advances into everyday care has often been slow and spotty, varying between parts of the country and even hospitals. Many studies have shown beyond doubt that a short list of drugs the so-called fab four or aspirin, beta blockers, cholesterol-lowering statins and ACE inhibitors can greatly improve survival after heart attacks. Guidelines from professional groups lay out precisely how these medicines should be used. Yet patients often are sent home without them. Even if doctors know the rules, some chafe at cookbook medicine, arguing that treatment must be individualized. Others may simply forget to follow all the steps in a busy practice. Still, experts say some treatments are just so basic that they should be offered to all patients unless there is a specific reason not to. We know human behavior in a helter-skelter environment requires reminders, said Dr. Kim Eagle, cardiology chief at the University of Michigan. His team helped Michigan hospitals set up procedures to make sure doctors and nurses follow the heart attack guidelines of the American College of Cardiology. The idea is to build reminders into every step of care, much like the checklists that pilots follow each time they take off, even though they know them by heart. In a presentation at the college’s annual scientific meeting, Eagle reported that lives were saved. He found that heart attack survival a year following discharge improved about 25 percent after hospitals made the changes. The potential impact of similar initiatives, if taken throughout the nation, is clearly profound, he said. The team compared the care at 33 hospitals on 2,857 elderly patients before and after they made the changes. All the patients were considered good candidates for the standard care. Prescriptions of aspirin, beta blockers, statins and ACE inhibitors significantly rose. For instance, use of beta blockers went from 84 percent of patients to 92 percent. Doctors at the hospitals use standardized forms for ordering treatment for their heart attack patients. This way, they must check off boxes showing whether they will use the standard drugs. Medical staff are given pocket guides and checklists, while patients receive information sheets and other data to help them remember what they are supposed to do. Dr. Robert Califf, director of clinical research at Duke University, said medical schools train doctors to believe they don’t need such step-by-step help, that they can rely instead on their understanding of biology to make decisions. He said fast food restaurants do a much better job of making sure ketchup and a napkin are stuffed into each bag than hospitals do assuring sick people are sent home with the right drugs. It’s easy to get excited about the next big drug, but if we just used the old drugs better, we could have a bigger effect, he said. Heart Patients Undertreated in ER, Despite New Tests Many heart attack patients admitted to the emergency room are going without drugs or surgical procedures that could extend their lives, despite blood test results indicating a need for more aggressive therapy, researchers report. A new study finds too many cardiologists downplaying the results of blood tests that measure levels of troponin. Even though we have these markers of risk available to us early in the patient’s hospital course, we don't always apply the therapies that we know are beneficial, says lead researcher Dr. Kristin Newby, a cardiologist at Duke University Medical Center. She presented the findings at the annual meeting of the American College of Cardiology in New Orleans. The American Heart Association now recommends that doctors focus on troponin test results when making treatment decisions, rather than on levels of creatine kinase-MB (CK-MB). But are doctors getting the message? In their study, Newby and her team examined the in-hospital medical records of almost 30,000 patients with suspected heart attack, all of whom were tested upon arrival at the ER for both troponin and CK-MB. They found that patients with dangerously high levels of both troponin and CK-MB did receive aggressive treatments like clot-busting drugs or interventional surgeries. But about 18 percent of patients admitted had discordant blood test results testing high for troponin, but low for CK-MB. Patients in this group tended to get less aggressive therapy, with doctors focusing on CK-MB and ignoring troponin. We tend to bias toward treating them like a lower-risk group, rather than acting on that troponin result, Newby says. We’re not doing a good job at applying what we see. The result, she says, are under-treated patients at higher risk for a second heart attack. Dr. Nieca Goldberg, a New York City cardiologist and an American Heart Association spokeswoman, says she’s dismayed by the findings. What’s surprising is the fact that, considering that these AHA guidelines have been out for a couple of years, and the troponin test is so widely and easily available, that it's not being used to its optimal potential. We really have to close this gap, she says. Goldberg suspects a lack of familiarity with the newer troponin test may be behind the trend. CK’s been around a lot longer and it’s clearly gotten into everyone’s clinical practice, she says. But from the study, it appears that we need to increase the utilization and interpretation of the troponin test in order to improve patient care. Should patients double-check that their therapy matches their test results? According to Goldberg, that's tough to do in the first hours or days of treatment. But Newby believes patients and their loved ones do have the right to ask questions as treatment continues into the longer term. If they hear they have a positive troponin, or they are told they have these proteins in their blood, they should ask, ‘Am I getting an aspirin? Should I take a statin? Should I be on a beta-blocker?’ Still, educating physicians remains key to more effective treatment, Newby says. Troponin is both newer and more specific for heart muscle damage than CK-MB. We know it does a better job at predicting who’s going to have another heart attack or who’s going to die after they have a heart attack. So it’s prognostically more helpful. One Pill to Quit Smoking and Lose Weight Soon the two leading health risks in the U.S., obesity and smoking, could be tackled by the drug Rimonabant delivered in a single pill, according to two university studies. Under development by the French firm Sanofi-Synthelabo, the drug is undergoing human tests by the company’s drug development arm in Malvern, PA, and could be ready for marketing approval next year. As a weight control drug, Rimonabant helped overweight people lose nine kilograms (20 pounds) in one year, improving levels of good cholesterol and reducing triglycerides in the bloodstream, according to a study by the University of Pennsylvania. Rimonabant was also found to help smokers almost double their odds of kicking the habit in 10 weeks, with overweight smokers losing half a kilo (one pound) of fat at the same time, according to another study by the University of Cincinnati. The drug blocks specific receptors in the brain and fat cells, inhibiting the urges to eat and light up, the French company said. Both studies found that the most common side effects of Rimonabant were nausea, dizziness and upper respiratory tract infections. Around 2,000 people took part in the two studies, which were presented at the annual meeting of the American College of Cardiology. Besides these studies, Sanofi-Synthelabo is also conducting five other trials involving 11,000 patients worldwide to examine Rimonabant's effect on smoking, weight loss, diabetes and cardiovascular risks. News of the promising drug coincided with a study by the US Centers for Disease Control and Prevention (CDC) showing that obesity could top smoking as the leading cause of preventable death among Americans by 2005. The number of deaths from poor diet and lack of exercise jumped by 33 percent between 1990 and 2000, while smoking-related deaths grew less than 10 percent, according to CDC estimates. If trends continue, the CDC said, the death toll from the fast-food, couch-potato lifestyle could pass the 500,000 mark next year, overtaking tobacco as the leading cause of preventable death for the first time in more than 40 years. Holiday Heart Attacks More Deadly If you go to a hospital with a heart attack during the holiday season, you are more likely to die than at other times of the year, researchers report. In addition, you are less likely to get medications such as aspirin and beta blockers. You are also less likely to undergo an angioplasty. People admitted during the winter holiday weeks were not only less likely to get proper therapy, but also had worse outcomes, says lead researcher Dr. Trip Meine, a cardiologist at Duke University Medical Center. Meine’s team collected data on 134,609 heart attack patients who were listed in the Cooperative Cardiovascular Project, which kept track of patients admitted to U.S. hospitals from 1994 to 1996. The researcher compared the treatment and outcome of the patients seen during the last two weeks of December and the first two weeks of January to those seen at other times. They found 77 percent of the patients admitted during the holiday weeks received aspirin compared with 78 percent at other times. There was also a difference in the use of beta blockers, with 43 percent receiving them on hospital admission during the holidays compared with 45 percent during the rest of the year. Moreover, only 13 percent underwent angioplasty during the holidays compared with 15 percent at other times, according to the report, which was presented at the American College of Cardiology’s annual scientific sessions. And perhaps worst of all, 23 percent of the patients admitted during the four weeks surrounding Christmas and New Year's died, compared with 21 percent during the rest of the year. Many studies have shown people are more likely to die from heart attacks during the winter holidays, but none of the studies looked at causes, Meine says. In their study, the researchers found the number of heart attack patients seen during the four-week holiday period was not different from any other four-week period in the year. Meine speculates that during these holidays the health-care system is strained, with lower staffing of doctors, nurses and medical technicians. This is the reason we saw less angioplasty, Meine says. And once you see less angioplasty, it is not surprising that mortality goes up. During periods when staffing is reduced, such as holidays, weekends and nights, patients suffer, Meine says. We need to do everything we can to minimize or prevent these periods. Health care needs to be like a casino: open 24 hours, seven days a week, with no difference in staffing any day or time. Dr. Stephen P. Glasser, a professor of epidemiology at the University of Minnesota, says the finding is not surprising, but he questions that understaffing is the reason for increased mortality. These problems may or may not be due to reduced staffing, he says. Other studies have shown that heart attacks tend to be more severe during the winter as well as more frequent, which may also account for the finding, Glasser says. It could also be factors we know nothing about, he adds. So it may have nothing to do with fewer angioplasties or medications, Glasser says. Understaffing as a reason for the findings has merit and makes sense, but whether it’s true or not is the question. Dr. Robert A. Kloner, a professor of cardiovascular medicine at the University of Southern California, notes that in his own research in Los Angeles, he found deaths from heart attacks are highest during December and January. Kloner speculates that colder weather, which causes higher blood pressure, is to blame. He also says the increase in heart attack deaths could be due to fewer hours of daylight or holiday stress, overeating and drinking. But hospital understaffing may also play a part, he says. Maybe hospitals need to schedule better and realize that winter holiday time is also the time most heart attacks occur.

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