News from The American Heart Association 2008 Scientific Sessions: November 9-12; New Orleans, Louisiana

Damage Inflicted During Cardiac Attacks More Widespread Than Previously Thought, Researchers Find

Cholesterol crystals released in the bloodstream during a cardiac attack or stroke can damage artery linings much further away from the site of the attack, leaving survivors at greater risk than previously thought. George Abela, a physician in Michigan State University’s College of Human Medicine and chief of the Department of Medicine’s cardiology section, is leading research into the role that the crystallization and expansion of cholesterol play in heart attacks, strokes and other cardiovascular events in humans. He presented his latest research at the American Heart Association’s Scientific Sessions meeting in New Orleans. In recent medical trials, Abela and his team of researchers tested carotid arteries in a laboratory by injecting cholesterol crystals into them. “Cholesterol has been shown to expand when crystallizing and then be released into the circulation following a cardiac event,” Abela said. “We found that the flow of sharp-ended crystals in arteries damage the lining of arteries and decrease the ability of arteries to dilate properly at intervals far away from the site of the attack.” Abela compared the process to a tree, with the trunk as the site of the cardiac event and the branches representing arteries where damage is afflicted far away from the trunk. “These findings have important clinical implications,” Abela said. “We found the original injury was being transmitted downstream. We may need to expand the testing that we have patients undergo to make sure more damage is not being done during a cardiac attack or stroke.” ___________________________

Philips Presents Technology to Improve Detection and Identification of Heart Disease

New cardiograph with 16-lead ECG algorithm technology may help diagnose hidden myocardial infarction; expands gender-based criteria for women, who may present symptoms differently Royal Philips Electronics unveiled a new cardiograph technology that helps improve detection and identification of problems in the heart, including specific coronary artery obstructions, damaged heart muscle and abnormal rhythms. On display at the American Heart Association’s (AHA) Scientific Sessions 2008, the new Philips PageWriter TC70 cardiograph, featuring Philips’ DXL16-Lead ECG Algorithm, may help clinicians deliver faster diagnosis and treatment during heart attacks, while also supporting door-to-balloon and hospital quality initiatives. While limb and chest leads have been traditional components of the 12-lead ECG, it has long been recognized that additional electrodes can provide information that is poorly or not seen at all on a traditional 12-lead ECG. The standard 12-lead ECG has a blind spot on the right side of the patient’s chest that limits the ability to detect right ventricular myocardial infarction (MI). DXL Algorithm technology addresses this issue by using electrodes placed on the right side to provide incremental capabilities not available with previous analysis programs. “We’re using right chest and posterior leads and see true patient benefits by diagnosing a hidden MI that we may not have picked up with a 12-lead ECG,” said Debbie Heinecke, RN, manager of Non-Invasive Cardiology at Blessing Hospital in Quincy, Ill., an early user of the new technology. Gender-specific criteria for women’s heart health. According to the AHA, one in three female adults in the U.S. has some form of cardiovascular disease and all cardiovascular diseases combined claim the lives of more than 400,000 American women annually — greater than all forms of cancer combined. Women often present cardiac symptoms differently from men and have a higher mortality rate from cardiovascular disease. The DXL Algorithm applies new gender, age and lead-specific STEMI (ST-segment elevation myocardial infarction) criteria to detect acute MI in women as well as men. A widespread pattern of ST depression often reflects global ischemia due to left main coronary obstruction, multi-vessel obstructions or microvascular disease, which is more prevalent in women. The DXL Algorithm incorporates new criteria for these conditions and provides a critical value of “global ischemia” to highlight that prompt intervention may be needed. Reference https://www.americanheart.org/downloadable/heart/1199816973854FS10WM08.pdf ___________________________

Boosting Medication Adherence in African-Americans

A patient education program that included self-affirmation and positive affect in the form of occasional gifts significantly increased medication adherence among African-Americans with high blood pressure, according to research presented at the American Heart Association’s Scientific Sessions 2008 (abstract 5131). The randomized, controlled trial found that calling patients occasionally with positive messages, coupled with standard information about hypertension, encouraged them to take their medication more often than patients who received usual care. “This is good news,” said Olugbenga Ogedegbe, MD, lead author of the study and an associate professor of medicine at the New York University School of Medicine. “We have a very cheap intervention that helps patients improve adherence. The key question here is ‘How do we integrate this into daily practice?’ ” Adherence — taking medication consistently and correctly — is a major issue in all patient populations and especially African-Americans. “African-Americans have been shown in some studies to be nearly twice as likely to not take their medicines when compared to Caucasians,” Ogedegbe said. For this study, researchers measured adherence, with electronic monitors installed on the caps of the blood pressure pill bottles. The monitors recorded each time the pill bottles were opened. Researchers consider this method far more reliable than patient self-report. The study of 252 African-Americans with hypertension found that those who received unexpected quarterly gifts by mail plus bi-monthly calls reminding them of positive life experiences took their medication 43 percent of the time over 12 months. Patients who just received a workbook on their disease with no additional intervention (control group) took their medicines 36 percent of the time during the year-long study. “The adherence level is still woefully low,” Ogedegbe said. Of the study patients, 80 percent were women, average age 58. All were prescribed at least one anti-hypertension medication. Although, most of the study participants were women, Ogedegbe expects the results to also apply to African-American men. Each patient in the study in the intervention group and in the control group received a 10-chapter hypertension education workbook that detailed ways to combat hypertension. Those in the intervention group also were called every two months with homework from the workbook along with reminders to think about proud moments in their lives, their goals and the values they hold dear. The calls were not costly, Ogedegbe said, because they came from research assistants with college degrees rather than medical professionals. The intervention group also received up to six small gifts unexpectedly throughout the 12-month study duration, which included an umbrella and a duffle bag. The items were adorned with positive messages such as, “It’s a beautiful day.” “The whole idea is to reduce the amount of negativity patients have in terms of their health,” Ogedegbe said. “If you are depressed, you are much less likely to take your medicine. This study attacked it from two ways by reducing the rate of depressed feelings and helping patients affirm their own positive feelings. When people receive unexpected good news or gifts it tends to induce positive feelings and it is shown to carry over into other areas of life.” ___________________________

Obese Children’s Artery Plaque Similar to Middle-aged Adults

The neck arteries of obese children and teens look more like those of 45-year-olds, according to research presented at the American Heart Association’s Scientific Sessions 2008 (abstract 6077). “There’s a saying that ‘you’re as old as your arteries,’ meaning that the state of your arteries is more important than your actual age in the evolution of heart disease and stroke,” said Geetha Raghuveer, MD, MPH, associate professor of pediatrics at the University of Missouri Kansas City School of Medicine and cardiologist at Children’s Mercy Hospital. “We found that the state of the arteries in these children is more typical of a 45-year-old than of someone their own age.” Researchers used ultrasound to measure the thickness of the carotid arteries. Increasing carotid artery intima-media thickness (CIMT) indicates the fatty buildup of plaque within arteries feeding the heart muscle and the brain, which can lead to heart attack or stroke. Investigators calculated CIMT in 34 boys and 36 girls who were “at-risk,” (average age 13, 89 percent white) and found: • These children had abnormal levels of one or more types of cholesterol — elevated levels of low-density lipoprotein (LDL), which is known as “bad cholesterol;” low levels of high-density lipoprotein (HDL), which is the “good cholesterol;” or high triglyceride levels. • Forty (57 percent) had a body mass index (BMI, a calculation of weight for height) above the 95th percentile. Their average CIMT was 0.45 millimeters (mm), with a maximum of 0.75 mm. The children’s “vascular age” — the age at which the level of thickening would be normal for their gender and race — was about 30 years older than their actual age, Raghuveer said. The children were deemed at high risk for future heart disease because of obesity, abnormal cholesterol, and/or a family history of early heart disease. On average, these children had: • Total cholesterol levels of 223.4 milligrams per deciliter (mg/dL) (less than 170 is considered acceptable by American Heart Association recommendations); • LDL cholesterol levels of 149.8 mg/dL (less than 110 is considered acceptable); and • Triglyceride levels of 151.9 mg/dL (below 150 is considered acceptable). Researchers found that having a higher BMI and higher systolic blood pressure had the most impact on CIMT. “Vascular age was advanced the furthest in the children with obesity and high triglyceride levels, so the combination of obesity and high triglycerides should be a red flag to the doctor that a child is at high risk of heart disease,” Raghuveer said. Further studies are needed to determine whether artery build-up will decrease if children lose weight, exercise or are treated for abnormal lipids. Some studies have shown that CIMT can be reduced when children at extremely high risk are treated with cholesterol-lowering statin medications, and that exercise can improve blood vessel function in children with a high BMI. “I’m optimistic that something can be done,” Raghuveer said. “In children, the buildup in the vessels is not hardened and calcified. We can improve the vessel walls and blood flow in adults through treatment, and I’m sure we can help children even more.” Other risk factors for high CIMT in children are high blood pressure, exposure to secondhand smoke and insulin resistance – which is frequently seen in obese children. ___________________________

Cell-coated Stent as Effective as DES, with Fewer Meds Needed

A stent that entices artery-lining cells to coat it works as well or better than drug-eluting stents in keeping arteries open in coronary heart disease patients, according to two research studies presented at the American Heart Association’s Scientific Sessions 2008 (abstracts 6000 and 4491/poster C184). The new endothelial progenitor cell-capturing (EPC) stent, OrbusNeich’s Genous, is coated with an antibody that binds endothelial progenitor cells circulating in the blood. A number of smaller, randomized studies have shown that the stent is effective in carefully selected patients. The new findings came from real-world patients. “Randomized trials have the advantage of a very good control group, but they usually have very restrictive exclusion and inclusion criteria; so results from randomized trials cannot be extrapolated to everyday patients,” said Sigmund Silber, MD, chief of cardiology at Müller Hospital Munich in Munich, Germany, and the first author of the large, multicenter stenting study. In one study (abstract 6000), Silber and colleagues reported the one-year outcomes of 1,640 patients treated with the stent in an international study conducted outside the United States. “The most significant finding was that the rate of stent blockage was really low,” Silber said. “The number of patients who needed another catheterized heart intervention within a year was also low.” Patients were treated at 144 sites around the world and entered into an electronic registry. Their average age was 62.8 years, 78.7 percent were males, 25.0 percent had diabetes, and 36.7 percent had suffered a prior heart attack. Based on results of previous studies, physicians pretreated 73.8 percent of the patients with statin drugs, which increase the number of endothelial progenitor cells in the blood. Most patients received two anti-clotting drugs, generally aspirin and clopidogrel, for one month. Researchers found that one year after stenting: • Only 1.0 percent of the patients suffered a stent-related thrombosis. • 2.1 percent of the patients died of cardiac causes; 1.8 percent of those were heart attacks. • 5.4 percent required a revascularization procedure on the treated artery; a catheter-based procedure was used in 5.1 percent to restore blood flow. • 9.3 percent experienced major adverse cardiac events (MACE), which included heart attacks, unexpected bypass surgery, treatment-related catheter-based revascularization, and cardiac death. • Among diabetic patients, 4.7 percent had undergone revascularization procedures, the major adverse cardiac events (MACE) rate was 10.3 percent, and 1.1 percent had stent-related thrombosis. “The stent appears very safe, even in diabetics,” Silber said. “I don’t think EPC-capturing stents will replace drug-eluting stents, but whenever you decide not to use a drug-eluting stent, this stent is a good alternative.” In a separate study (abstract 4491), researchers reported the one-year clinical outcome of 236 mainly high-risk patients treated with an EPC-capturing stent at the Academic Medical Center of the University of Amsterdam in The Netherlands. Until recently, two types of stents were used in daily practice; the bare-metal stent and the drug-eluting stent. “The long-term safety concerns of the drug-eluting stent are late stent thrombosis and an associated increased risk of bleeding, due to long-term dual antiplatelet therapy.” said Margo Klomp, MD, first author of the Amsterdam study and a medical fellow at the Academic Medical Center. In the single-center Dutch study, Klomp and her colleagues reported on patients with mainly complex lesions who were stented at the Amsterdam center between September 2005 and March 2007. The patients averaged 65 years of age, 72 percent were male and 14 percent had diabetes. The researchers’ one-year follow-up findings included: • 3.0 percent of the patients died, of whom 0.8 percent died of cardiac causes. • 10.2 percent required a repeat revascularization procedure of the treated vessel. • 1.2 percent (3 patients) had suffered stent thrombosis, which were angiographically documented and occurred within 24 hours, at seven days, and at 18 days, respectively. • The MACE rate, composed of cardiac death, target lesion revascularization and myocardial infarction, was 13.6 percent. “Further research on the stent is being performed in a two-armed study, the TRIAS Program, at the Academic Medical Center,” Klomp said. “In one arm, TRIAS LR, the EPC-capturing stent is being compared with the bare-metal stent in patients with a low risk of develop a new blockage. In the other arm, TRIAS HR, the EPC-capturing stent is being compared with conventional drug-eluting stents in people with a high risk of restenosis.” OrbusNeich funded the international study. ___________________________

American College of Cardiology (ACC)/American College of Gastroenterology (ACG)/American Heart Association (AHA) Joint Comment on Studies Regarding Possible Interaction of Clopidogrel and Proton Pump Inhibitors

Two studies released at the American Heart Association Scientific Sessions 2008 came to opposite conclusions in studying whether a class of heartburn drugs called proton pump inhibitors (PPIs) alter the ability of clopidogrel, an anti-platelet drug, to prevent cardiovascular events after stent placement. American College of Cardiology (ACC)/American Heart Association (AHA) guidelines and statements recommend dual anti-platelet therapy (aspirin plus a thienopyridine such as clopidogrel) following stent placement. Previous research shows that combining a PPI with clopidogrel lessens the risk of GI bleeding. However, other recent studies have suggested that adding a PPI could blunt clopidogrel’s anti-platelet effect. This interaction has not been studied in large numbers of patients, so there is no definitive evidence that the use of PPIs will keep clopidogrel from working to prevent cardiac events. Neither of the studies presented provides sufficient evidence to change clinical practice. In the interest of patient safety, the AHA/ACC and the American College of Gastroenterology (ACG) advise that patients who are currently taking these medications should not change their medication regimen unless advised by their healthcare provider. The first study (abstract 3998) reviewed major adverse cardiac events (hospitalization for stroke, heart attack, angina or bypass surgery) over one year in patients prescribed clopidogrel after stent placement. The study group included 14,383 patients in the Medco Integrated Database who were at least 80 percent compliant with refilling their medication. Patients who took clopidogrel alone were compared with those taking clopidogrel and PPIs. The study found that patients receiving both medications had significantly more major cardiovascular events in a year than patients taking clopidogrel alone. However, the patients taking both medications had a higher cardiovascular risk factor profile (age, gender, diabetes, hypertension, chronic kidney disease). There are several significant limitations to this type of study, as acknowledged by the authors. The database did not include information about participants’ use of over-the-counter drugs (including aspirin or omeprazole) and could not account for other cardiovascular risk factors such as family history, smoking status, blood pressure levels and lipid values. As the authors themselves concluded, further investigation should focus on prospective study of this interaction. The second study (abstract 3999) reported no adverse effect of combining a PPI with clopidogrel. The CREDO trial previously found a benefit of one year vs. one month of treatment with clopidogrel after coronary stenting. The sub-group analysis reported today assessed the endpoint of death, myocardial infarction (MI) or stroke in patients on clopidogrel or placebo with or without a PPI, and showed no adverse effect of combining a PPI with clopidogrel. Patients treated with a PPI were at higher baseline risk and had a worse outcome compared to those who were not, whether they were given placebo or clopidogrel. The ongoing COGENT-1 study is randomizing patients with coronary artery disease to ASA plus clopidogrel in combination with 20 mg of omeprazole (a PPI) or placebo and should provide further evidence to help address these issues. Other clinical trials are needed. ___________________________

Umbilical Cord Blood May Help Build New Heart Valves

Children with heart defects may someday receive perfectly-matched new heart valves built using stem cells from their umbilical cord blood, according to research presented at the American Heart Association’s Scientific Sessions 2008 (abstract 3087). When infants are born with malfunctioning heart valves that can’t be surgically repaired, they rely on replacements from animal tissue, compatible human organ donations or artificial materials. These replacements are lifesaving, but don’t grow and change shape as a child develops; so two or more surgeries may be needed to replace outgrown valves. The animal tissue may also stiffen over time and be less durable than a normal human valve. With artificial valves, children also must be treated with blood thinners. “In our concept, if prenatal testing shows a heart defect, you could collect blood from the umbilical cord at birth, harvest the stem cells, and fabricate a heart valve that is ready when the baby needs it,” said Ralf Sodian, MD, lead author of the study and a cardiac surgeon at the University Hospital of Munich. The tissue engineering of heart valves is still in its infancy, with various researchers investigating the possibility of using cells from blood, bone marrow or amniotic fluid. In the study, the research team used stem cells (CD133+ cells) derived from umbilical cord blood. The cord blood was frozen to preserve it. After 12 weeks, the cells were seeded onto eight heart valve scaffolds constructed of a biodegradable material and then grown in a laboratory. Afterwards, examination using electron microscopes revealed that the cells had grown into pores of the scaffolding and formed a tissue layer. Biochemical examination indicated that the cells had not only survived and grown, but had produced important elements of the “extracellular matrix,” the portion of body tissue that functions outside of cells and is essential to tissue function and structure. Compared with human tissue from pulmonary heart valves, the tissue-engineered valves formed: • 77.9 percent as much collagen (the main protein in connective tissue); • 85 percent as much glycosaminoglycan, a carbohydrate important in connective tissue); and • 67 percent as much elastin (a protein in connective tissue). Furthermore, using antibodies to detect various proteins, the researchers found the valves contained desmin (a protein in muscle cells), laminin (a protein in all internal organs), alpha-actin (a protein that helps muscle cells contract) and CD31, VWF and VE-cadherin (components of blood vessel linings). “These markers all indicate that human cardiovascular tissue was grown in the lab,” Sodian said. Several important questions remain to be solved regarding tissue-engineered functional heart valves, including identifying the optimal scaffold material and learning how to condition the valves in the laboratory so they work properly after being implanted, Sodian said. “Tissue engineering provides the prospect of an ideal heart valve substitute that lasts throughout the patient’s lifetime and has the potential to grow with the recipient and to change shape as needed,” he said. ___________________________

Heart’s Surplus Energy May Help Power Pacemakers, Defibrillators

Surplus energy generated by the heart may one day help power pacemakers and defibrillators implanted in cardiac patients, according to research presented at the American Heart Association’s Scientific Sessions 2008 (abstract 2165/poster C56). In a trailblazing experiment, a microgenerator powered by heartbeats produced almost 17 percent of the electricity needed to run an artificial pacemaker. The innovative generator — called the self-energizing implantable medical microsystem (SIMM) — helps the heart produce more than enough energy with each beat to pump blood. The SIMM uses two compressible bladders and a microgenerator mounted on the lead of a pacemaker or defibrillator, the wire that connects the device to the heart. The lead is attached to the end of the right ventricle, and the bladders relay the energy from the pressure of each heartbeat to the microgenerator, which transforms it into electricity for use by the battery. “This was a proof-of-concept study, and we proved the concept,” said Paul Roberts, MD, first author of the study and a consultant electrophysiologist at Southampton University Hospital in the United Kingdom. “Harvesting surplus energy might be a major transition in implantable pacemakers and defibrillators because engineers will have more energy to work with.” In their study, researchers found: • At a heart rate of 80 beats per minute (bpm), the device yielded an average harvested energy of 4.3 microjoules per cardiac cycle. • Increasing changes in the heart rate produced corresponding increases in energy. At 104 to 128 bpm, the harvested energy level increased 140 percent. • Decreases occurred when the researchers slowed the heartbeat or lowered blood pressure. • Implantation and surplus energy harvesting caused no significant injury to the lining of the heart’s chambers. “What this might mean is that in the next era of pacemakers, you’d get devices that lasted significantly longer and we could add more functions to help monitor the heart,” Roberts said. “It’s possible they could be efficient enough to allow complete and indefinite powering of pacemakers.” Since their introduction into clinical medicine, implantable pacemakers and defibrillators have saved lives and become more sophisticated. However, adding new monitoring capabilities to the devices has led designers to a critical point. “The small devices now are really very good, but power consumption must increase if we want to take them to the next level,” Roberts said. “Battery technology has plateaued and the only way we are going to increase power is to increase size.” This, in turn, would increase the units’ weight, making them more uncomfortable and less cosmetically acceptable to patients because the devices are implanted under the skin. A consortium of companies including InVivo Technology, Perpetuum and Zarlink Semiconductor developed and tested the SIMM microgenerator with United Kingdom government funds. Researchers used an in-vivo porcine model to evaluate the study. The researchers are now working to improve the materials used in the SIMM microgenerator. “With different materials, we’re seeing even greater energy harvesting,” Roberts said. “While at the moment we see about 20 percent harvesting, we’re anticipating that will be significantly more in the next iteration of the device.” ___________________________

DES Beat BMS in Diabetics

Drug-eluting stents reduced the risk of revascularization, heart attack and death in diabetics as compared with bare-metal stents in the largest observational comparison, researchers reported at the American Heart Association’s Scientific Sessions 2008. The results, from The Drug-eluting and Bare Metal Stenting in Patients with Diabetes Mellitus: Results from the Mass-DAC Registry, were presented as a late-breaking clinical trial. The study is simultaneously published in Circulation: Journal of the American Heart Association. “We actually saw a significant benefit from using drug-eluting stents in this patient population,” said Laura Mauri, MD, MSc, principal investigator of the study and assistant professor of medicine at Brigham and Women’s Hospital and Harvard Medical School in Boston, Mass. “First, they significantly reduced the need for repeat procedures which included repeat stenting or bypass surgery. Second, they were associated with lower rates of death and heart attack. So, as a result we can say that these stents appear to be safe in diabetic patients, whose diabetes puts them at higher risk of mortality and heart attack than the general population.” In the largest population-based comparison of stents in diabetics, researchers used data from a mandatory state registry. They identified 5,051 diabetics who underwent PCI at acute-care, non-federal hospitals between April 2003 and September 2004. Diabetic patients at those hospitals were about twice as likely to get DES compared to BMS (66.1 percent vs. 33.9 percent), researchers said. At three years of follow-up, the unadjusted cumulative endpoint of death was 14.4 percent for DES patients compared to 22.2 percent for BMS patients, Mauri said. The researchers then matched a subset of 1,476 DES and 1,476 BMS patients to control for 63 potential confounders such as concurrent conditions and medications. In that comparison, they found the risk-adjusted mortality at three years was 17.5 percent for DES patients vs. 20.7 percent, a small but significant 3.2 percent absolute reduction in mortality in DES patients, with no excess adverse events. The choice of BMS or DES was not randomized, but was done at the direction of the treating physician, so it is possible that the patients given DES were different in the number of blood vessel or other characteristics. Although three-year data were not yet available for rates of heart attack and target vessel revascularization, at two years of follow-up those rates were lower in the DES group compared to the BMS group. “Diabetic patients represent a large and growing proportion of patients who undergo stenting,” Mauri said. “We know that patients with diabetes have a higher incidence of adverse events following the procedure, including higher rates of restenosis, heart attack and death related to heart problems.” “Previous studies indicated that drug-eluting stents reduce the rate of restenosis, but there has been controversy about their safety because of conflicting evidence from smaller studies.” Some of those studies found higher mortality associated with DES while others found no safety differences between the two types of stents. This study showed lower mortality and adverse events. The Massachusetts Data Analysis Center (Mass-DAC) registry is a special resource to research outcomes after PCI, since the state department of public health requires that every non-federal hospital provide procedural information and outcomes for every adult who undergoes PCI. Such data are intended to monitor and to improve the quality of patient care. “Through an effort headed by the Division of Health Care Quality at the Massachusetts Department of Public Health, we were able to use clinical data collected from every non-federal hospital in the state that treats patients with stents to monitor safety of the drug-eluting stents,” said Sharon-Lise Normand, PhD, co-author of the study, director of the Mass-DAC and professor of health care policy (biostatistics) at Harvard Medical School and Harvard School of Public Health. “Surveillance systems such as this are critical to assessing quality and safety in the real-world.” ___________________________

Study Finds Timing is Everything for Some Heart Attack Patients

There is strong evidence that getting to the hospital quickly during a heart attack is critical, since early treatment saves both lives and heart muscle. And if the responsible coronary artery is completely blocked, it should be opened as soon as possible. What about patients with incomplete blockages, who have acute coronary syndrome (ACS)? They should get to the hospital just as fast, but once there and on medical treatment, do they need to race to the cath lab? Not always, researchers said, regarding the TIMing of Intervention in Acute Coronary Syndrome (TIMACS) study, presented as a late-breaking clinical trial at the American Heart Association’s Scientific Sessions 2008. The study of 3,031 patients treated at 100 medical centers in 17 countries was a prospective comparison of the relative usefulness, safety and cost effectiveness of early (within 24 hours) angiography, followed by revascularization if necessary, versus a delay of more than 36 hours after the onset of unstable angina or non-ST segment elevation myocardial infarction (NSTEMI). An early diagnostic angiogram reduced the relative risk of the composite endpoint of death, second heart attack or stroke by 35 percent in a high-risk subset of patients with a heart attack not demonstrating ST segment elevation on the EKG. But for many patients, the slower strategy appears to be just as good. “If you are at low risk or intermediate risk for death with ACS, it doesn’t matter whether you have your angiogram early or late, but if you are at high risk, the early intervention strategy is far better,” said Shamir R. Mehta, MD, MSc, study author, director of interventional cardiology at Hamilton Health Sciences Corp. and associate professor of medicine at McMaster University, Hamilton, Canada. About two-thirds of the patients in the study were in the low or intermediate risk groups. The study of 3,031 patients treated at 100 medical centers in 17 countries was a prospective comparison of the relative usefulness, safety and cost effectiveness of intervention as soon as possible (and within 24 hours) versus a delay of more than 36 hours after unstable angina or NSTEMI. For the primary endpoint, a composite of death, recurrent heart attack or stroke within six months, the researchers found no significant risk reduction (p = 0.15) in favor of early intervention. However, striking results emerged when the researchers compared patients based on their Grace Risk Score, a way of predicting the risk of dying within the next six months based on factors like age, other medical conditions, kidney function and a history of heart failure. Among the 961 patients who measured >140 on the Grace Risk Score, the primary endpoint was seen in 21.6 percent of the late intervention group versus 14.1 percent of the high-risk patients, a 35 percent reduction in relative risk that was of high statistical significance (p value = 0.005), indicating a clear benefit for early coronary angiography and treatment, he said. “This is by far, the largest study of ACS to study the ideal timing for intervention,” he said, adding that an earlier trial on the issue was too small to provide a conclusive answer. “Randomized trials have shown the benefit of coronary artery bypass grafting and percutaneous coronary intervention (PCI) in patients with this form of acute coronary syndrome (ACS), however the optimal timing of those interventions is unknown,” he said. Several studies comparing STEMI and non-STEMI heart attacks have found that STEMI patients tend to fare better, leading to the hypothesis that the timing of treatment may be a factor, Mehta said. Angiography may not be available at small, rural hospitals, he added. “If the early strategy is better than delayed in the high-risk patients, then it might be appropriate to bypass small hospitals that lack invasive facilities and take those patients directly to an invasive center,” he said. ___________________________

Tailored Drug Delivery Reduces Adverse Effects After PCI

Individually tailored anti-clotting medication dosing significantly cut the rate of adverse events after non-emergent percutaneous coronary intervention (PCI) with stenting, researchers reported at the American Heart Association’s Scientific Sessions 2008. Results of the Tailored Clopidogrel Loading Dose According to Platelet Reactivity Monitoring to Prevent Stent Thrombosis study were presented as a late-breaking clinical trial. Individuals respond differently to clopidogrel, with a significant number deemed “low responders,” those having a reduced response to the drug. That led to the hypothesis that an individualized approach might magnify the benefits of clopidogrel, said Franck Paganelli, MD, PhD, author of the study and professor of medicine in the division of cardiology, Hopital Nord (North Hospital), University of Marseille, School of Medicine, Marseille, France. The researchers studied 429 low responders, including 214 in the control group who got usual care with one 600 milligram (mg) dose of clopidogrel. The test group received up to three more doses of clopidogrel every 24 hours with a goal of reducing their score to the cut-off level on a VASP phosphorylation analysis, a blood test that measures a patient’s anti-platelet response to clopidogrel. The primary endpoint was the rate of early definite stent thrombosis. That was defined as a total blockage or visible thrombus originating in or within 5 millimeters (mm) of the stent and associated with symptoms or diagnostic signs of reduced blood flow to the heart muscle within 48 hours of the procedure. The secondary endpoints were the rate of a composite of major adverse cardiac events (MACE), which included myocardial infarction and cardiovascular death, or urgent revascularization procedures, as well as the separate endpoint of bleeding. Despite additional doses of clopidogrel up to a total of 2400 mg, 8 percent of the low-responders remained with a low response. However, the tailored approach significantly lowered the primary and secondary event endpoints without significantly increasing bleeding events, said Paganelli. The rate of early definite stent thrombosis was 0.5 percent in the tailored-dosage patients versus 4.2 percent in the controls (p Hispanics Less Likely to Have Repeat Revascularizations One Year After Angioplasty Hispanic patients were 57 percent less likely than Caucasian patients to undergo coronary artery bypass surgery (CABG) one year after successful angioplasty. Hispanics also had a trend toward lower rates of overall repeat revascularization procedures including stenting and bypass surgery, according to a study presented at the American Heart Association’s Scientific Sessions 2008 (abstract 916/poster C214). The study also found half of Hispanics undergoing PCI had diabetes. They also were more likely to have longer lesions, with the average length of 15.4 millimeters (mm) compared to 14.1 mm in Caucasians. “More Hispanics have hypertension and diabetes, especially insulin-treated diabetes,” said Shailja V. Parikh, MD, a fellow in the Department of Internal Medicine, Division of Cardiology, at the University of Texas Southwestern Medical Center in Dallas. The study — one of the first to examine restenosis rates in Hispanics — included 542 Hispanics and 1,357 Caucasians undergoing PCI from the National Heart, Lung, and Blood Institute (NHLBI) Dynamic Registry Waves from 1999 to 2006. Only clinical centers where 5 percent of patients were of Hispanic ethnicity were included. Despite Hispanic patients being an average three years younger, researchers found more: • Hypertension – 80.4 percent versus 72.3 percent in Caucasians; • Diabetes – 49.2 percent versus 27.8 percent in Caucasians; and • Insulin-treated diabetes – 15 percent versus 7.4 percent in Caucasians. Hispanic participants had less: • Peripheral vascular disease – 5.6 percent versus 10.3 percent; • Prior heart attack – 25.8 percent versus 30.9 percent; and • Prior PCI – 27.8 percent versus 34.1 percent than Caucasians. Researchers found that rates of death and heart attack were similar between Hispanics and Caucasians one year after PCI. “It’s interesting that Hispanics were younger and had more risk factors,” Parikh said. “With higher rates of Type 1 diabetes, hypertension, and longer lesion lengths, one would expect Hispanic patients to have higher rates of repeat revascularization either though CABG or PCI. However, despite having these risk factors for increased rates of restenosis, Hispanics were found to be revascularized less often after initial PCI than their Caucasian counterparts. “It is possible that a referral bias exists in which Hispanic patients are not being referred for coronary artery bypass surgery as commonly as Caucasians,” Parikh said. “Or, there may be mediating factors intrinsic to the Hispanic patient that could be protective toward restenosis.” Parikh advocates for increased preventive measures and for modification of risk factors among these patients before they reach the cath labs. Better control of the unique set of risk factors in Hispanics could decrease the need for downstream invasive interventions. Parikh and colleagues are planning to do further research on Hispanics in Dallas, where one-third of all patients undergoing cardiac catheterization at the Parkland Memorial Hospital catheterization laboratories are Hispanic. According to the American Heart Association, data from the National Health Interview Survey 2005 study of the National Center for Health Statistics showed that among Hispanics/Latinos age 18 and older, 8.3 percent have heart disease, 5.9 percent have coronary heart disease, 20.3 percent have hypertension, and 2.2 percent have had a stroke.

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