Industry News

News from the American Heart Association Scientific Sessions (AHA)

Low Cost Drug Helps Reduce Deaths, Repeat Heart Attacks Reviparin is simple, effective therapy for heart attack patients worldwide A major Canadian-led global study has found that an inexpensive anti-blood-clotting drug significantly reduces death and repeat heart attacks without increasing the risk of stroke. The study is of significance to patients in all countries, including developing countries where access to high-tech treatments for cardiovascular problems may be limited. The CREATE randomized trial was initiated and coordinated in Canada and enrolled more than 15,500 people in China, India and Pakistan. Heart attack patients were given Reviparin, a low molecular weight heparin, or a placebo, twice daily for 7 days. The four-year study showed that the risk of deaths, heart attacks and strokes were reduced by about one-sixth. This means that treating 1,000 patients for a week would prevent about 15 to 20 individuals from dying or suffering a new heart attack. The study also showed that the benefits were greater, the earlier the treatment was used after the onset of symptoms. In those who were treated within two hours of symptom onset, the death rate was lowered by about 30%. The study was presented today at the Scientific Sessions of the American Heart Association conference in New Orleans by co-investigators Dr. Salim Yusuf and Dr. Shamir Mehta of the Population Health Research Institute at Hamilton Health Sciences and McMaster University. Reviparin is a simple and relatively inexpensive anti-thrombotic therapy, which can be used in both developed and developing countries to reduce mortality for acute myocardial infarction, said Dr. Yusuf. It is more affordable than newer anti-thrombotics, simple to use and of benefit in addition to the broad range of therapies of proven and established value. It is the only treatment for a heart attack that has been convincingly demonstrated to reduce mortality in a single study over the last decade. Dr. Mehta said: The reduction in mortality with Reviparin is truly remarkable since no other drug in this class has shown similar benefits and the fact the drug was tested on top of already proven therapies. About 15.5 million people die worldwide from cardiovascular deaths each year and about half of these are due to acute myocardial infarction, with the majority occurring in low and middle-income countries, Dr. Yusuf noted. Low cost therapies are obviously more invaluable than expensive ones, he said. This therapy could be used not only in wealthy countries, but also in small medical centres in low and middle income countries. It has the potential to benefit more than a million individuals annually. In a companion study, also presented at the American Heart Association meeting, Drs. Mehta and Yusuf evaluated the role of high dose glucose-insulin-potassium (GIK) solution in 20,000 patients. The solution is thought to preserve heart muscle and prevent it from dying during the acute stages of a heart attack. The study results show that GIK had a neutral effect, but the authors wonder whether a solution that had a lower glucose concentration may be of benefit. It is important to conduct large studies of promising agents to determine whether or not they are of value, said Dr. Mehta. While demonstrating that something is of benefit is wonderful, reliably excluding agents are not helpful is equally important as it will avoid their unnecessary use and associated costs. This is particularly important for therapies such as GIK that may never otherwise be studied because they are of no commercial value but have the promise to help many thousands of lives. New Clinical Trial Data Showed the Addition of Integrilin® (Eptifibatide) Injection Achieved Superior Platelet Inhibition and Less Heart Muscle Damage When Compared to a Commonly Used Antiplatelet Regimen Alone Millennium Pharmaceuticals, Inc. announced that in the CLEAR Platelets (Clopidogrel Loading with Eptifibatide to Arrest the Reactivity of Platelets) trial, the addition of eptifibatide, a glycoprotein (GP) IIb-IIIa inhibitor, to a commonly used antiplatelet regimen provided superior platelet inhibition and prevention of heart muscle damage associated with elective coronary stenting in the low-to-moderate risk study patients. Results from CLEAR Platelets were presented at the 2004 American Heart Association Scientific Sessions meeting in New Orleans. The CLEAR Platelets study supports the use of eptifibatide as a critical component in acute cardiovascular care. The patients in this study are representative of a real-world population that is often not pretreated with clopidogrel or other agents. Their underlying conditions include risk factors such as hypertension, smoking and diabetes, said Paul Gurbel, MD, principal investigator in the CLEAR Platelets study, director of Sinai Center for Thrombosis Research at Sinai Hospital of Baltimore and associate professor at Johns Hopkins University, Baltimore. Our findings show that the addition of eptifibatide with either a high or standard dose of clopidogrel provided an optimal platelet inhibition strategy, and were associated with the lowest incidence of heart muscle damage, also known as myocardial necrosis. In the study, patients receiving the combination of eptifibatide and clopidogrel had the lowest platelet reactivity over 24 hours compared to patients receiving clopidogrel alone (pAngioplasty, Robotically Assisted Keyhole Bypass Combo Appears Effective Combining stented angioplasty and robotically assisted keyhole bypass surgery is safe and may help patients with extensive cardiovascular disease, researchers reported at the American Heart Association’s Scientific Sessions 2004. Doctors performed the hybrid approach on 12 patients, all of whom remain free of chest pain, said Bernard De Bruyne, MD, PhD, co-author of the report and head of the Catheterization Laboratory at the Cardiovascular Center in Aalst, Belgium. This technique puts together the best of both worlds, De Bruyne said. However, it is important to emphasize that this is a small pilot study, and that robotically enhanced minimally invasive direct coronary artery bypass (MIDCAB) is a recent technique that is used in only a few centers Robotically enhanced MIDCAB is a minimally invasive procedure in which one or both internal mammary arteries (in the chest) are harvested with the help of a robot. Doctors then suture them to the obstructed coronary arteries through a left, keyhole mini-thoracotomy (about 2 inches wide) to supply blood below the obstruction. The fact that this key-hole surgery is performed without opening the chest and without arresting the heart offers patients the best postoperative comfort level and aesthetic results, said Frank Van Praet, MD, senior author of the report and staff member of the department of cardiovascular and thoracic surgery at the OLV clinic in Aalst, Belgium. Keyhole surgery involves cutting two small holes in a patient’s chest, in addition to a larger hole (the mini-thoracotomy). The surgeon inserts a small light into the chest through one hole and a camera through the other. Surgical instruments are used in the larger hole. The surgeon holds instrument-like tools connected to a computer. Observing the heart on a monitor, the surgeon performs the delicate motions required by the operation. The computer interprets the surgeon’s movements and maneuvers the instruments performing the surgery. The computer eliminates the slightest tremor in the surgeon’s hands for a less risky operation. Keyhole surgery is much less invasive than regular bypass operations, and patients recover more quickly with less pain and scarring. The procedure is for patients whose arteries are not suitable for angioplasty. The hybrid approach has been reported before, but this is the first hybrid bypass performed without opening the chest and on a beating heart, De Bruyne said. There are few patients involved, but we needed to be certain that it could be done safely. This combined technique might be applied to many similar patients. We had absolutely no complications with this approach. If confirmed in larger trials, combining the two procedures should especially benefit patients with diabetes and coronary heart disease and patients whose narrowed arteries include chronic obstruction of the left descending coronary artery (LAD). Patients in the study underwent their procedures between July 2002 and December 2003. All had narrowing in the heart’s three main arteries, including obstructions in the LAD that precluded treatment with angioplasty. Eleven patients were first treated with angioplasty in the right coronary artery or left circumflex artery an average of 41 days prior to their bypass operation. One patient had angioplasty on both. The 12th patient underwent angioplasty three days after surgery. A combination of bare-metal stents and the Taxus stent (Boston Scientific Corporation) were used. Patients had a follow-up angiogram within a week after the surgical procedure, proving the patency of all bypass grafts and stented segments (when performed prior to the operation). Patients had a clinical follow-up after six weeks and six months. During the six-month follow-up, none died, had heart attacks or needed additional procedures to re-open arteries. All patients were free of typical angina. I. Sirolimus-Eluting Stent Clinical Trial Yields Positive Results For Diabetic Patients With Heart Disease New Study Finds Low Incidence of Repeat Coronary Procedures in Insulin-Dependent and Non-Insulin Dependent Diabetics Results from a prospective, independent clinical study show a low incidence of repeat coronary procedures in insulin-dependent (IDDM) and non-insulin-dependent (non-IDDM) diabetic patients who received a Cypher® sirolimus-eluting coronary stent to treat restenosis, as compared to patients without diabetes who received the stent. The findings of the Washington Hospital Center (Washington D.C.) study were presented at the 2004 American Heart Association Scientific Sessions. Both insulin-dependent and non-insulin dependent patients treated with the Cypher stent had extremely low rates of adverse events, defined as the need for retreatment, or the occurrence of heart attacks and death. Specifically, the study found no statistical difference in clinical results between the two patient groups, revealing that diabetic patients faired as well statistically as the patients who did not have diabetes. One thousand four hundred and seven patients were enrolled in the study, divided into three groups: insulin dependent diabetics (11.3 percent, or 160 patients), non-insulin dependent diabetics taking oral agents and/or on dietary control (23.6 percent, 332 patients) and patients who did not have diabetes (65 percent, or 915 patients). Follow-up evaluations were conducted for all groups following the procedure and at one-month and six-months post-procedure. Six-month follow-up showed no significant differences with regard to mortality (4.5 percent in non-IDDM; 3.8 percent in IDDM and 2.3 percent for non diabetic); target lesion revascularization, also known as TLR (0.9 percent in non-IDDM; 0.4 percent in IDDM; and 1.5 percent in non-diabetic); and overall MACE calculated with target vessel revascularization, also known as TVR (8.0 percent in non-IDDM; 7.9 percent in IDDM and 6.2 percent in non-diabetic). II. Elderly Patients With Coronary Artery Disease Benefit From Drug-Eluting Stents Results With the Cypher® Stent Show Encouraging Safety and Efficacy Data for Aging Octogenarian Population Elderly patients treated with the Cypher® sirolimus-eluting coronary stent should expect the same benefit in repeat coronary procedures as seen with younger patients, according to a report presented at the 2004 American Heart Association Scientific Sessions. The data were taken from the e-CYPHERSM Registry, which was designed to better understand the safety and clinical benefits of the Cypher stent in treating coronary artery disease in difficult-to-treat patient groups. The octogenarian group, comprised of 505 patients aged 80 years or older, had a low target lesion revascularization (TLR) rate, which was similar to the rate in the patient group under the age of 80 (0.8 percent vs. 1.3 percent). As a result, another key endpoint of the analysis, Major Adverse Cardiac Events (MACE), which includes heart attacks, TLR and death, was also low for the elderly population (6.3%). Importantly, the late stent thrombosis rate was not significantly higher for the elderly patients (0.2% vs 0.14%). Among the elderly group treated with the Cypher Stent in the study, 39.5 percent were female, 44.8 percent had unstable angina, 15.5 percent had restenotic lesions and 35.6 percent had three-vessel disease. The analysis was based on six-month follow-up data from the international e-CYPHERSM registry, which tracks use of the Cypher Stent in more than 15,000 patients worldwide. The e-CYPHERSM Registry has currently collected baseline, procedure and follow-up information from 15,000 patients treated in 281 centers. Data Prove Value of Providing ICD Therapy to Those at Proven Risk of Sudden Cardiac Arrest In March, results from the landmark Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) showed that ICDs reduced death by 23 percent in people with moderate heart failure and poor heart pumping function, compared to those who did not receive defibrillators. New data presented at the American Heart Association Scientific Sessions indicate that the cost to add one year of life for these heart failure patients with an implantable defibrillator is $33,192. Medical therapies that add a patient year of life for $50,000 or less, such as primary coronary stenting, are commonly considered to be cost-effective treatments. The results of the cost-effectiveness analysis were notably consistent across predetermined patient subgroups. The conclusion from this cost analysis is clear: Implantable defibrillators represent an economically attractive way to save lives in many people who have moderate, stable heart failure due to a damaged heart muscle, said Daniel Mark, MD, MPH, Duke Clinical Research Institute and primary investigator for SCD-HeFT economics research. SCD-HeFT was a randomized, placebo-controlled, three-arm trial examining the use of ICD therapy and anti-arrhythmic drug therapy in 2,521 patients who have moderate heart failure (New York Heart Association Class II or III), plus impaired pumping function of the left ventricle. One-third of the patients enrolled in the study received an ICD provided by Medtronic. Another third received amiodarone and one-third received a placebo. All patients in the trial received optimal conventional heart failure medications as tolerated, including ACE inhibitors and beta-blockers, and when appropriate, diuretics, statins and aspirin. Sponsored by the National Institutes of Health, with funding from Medtronic and Wyeth Pharmaceuticals, patient enrollment began in 1997 and continued through 2001. The economic analysis was performed by measuring the costs of all three treatment arms and calculating the extra costs associated with ICD therapy and amiodarone. Since amiodarone showed no improvement in survival over placebo, cost-effectiveness analysis involved only the ICD and placebo arms. The cost-effectiveness was based on the extensive empirical data collected as part of the SCD-HeFT research effort, and statistical modeling was used to project survival and costs beyond the end of the study follow-up period, as is standard in cost-effectiveness analysis. Hedgehog Pathway Restores Cardiac Function in Preclinical Models of Heart Attack Studies demonstrate key role of Hedgehog signaling pathway in development of new blood vessels to promote cardiac recovery Curis, Inc., a therapeutic drug development company, announced that two new reports have documented the beneficial effects of Hedgehog pathway stimulation for increasing blood flow to damaged heart muscle and promoting improved cardiac function following both acute and chronic myocardial ischemia in preclinical models of heart disease. The two new studies were presented as abstracts at the annual meeting of the American Heart Association’s Scientific Sessions. The research for these studies was performed in the laboratory of Dr. Douglas Losordo in the Division of Cardiovascular Research at the St. Elizabeth’s Medical Center of Boston, Massachusetts. The authors conclude that activation of the Hedgehog signaling pathway after an acute heart attack or chronic cardiac ischemia promotes recovery of heart function by stimulating blood vessel growth factors and other regeneration factors that limit scar formation, preserve cardiac muscle tissue, and promote improved heart function. Previous scientific reports from Dr. Losordo’s laboratory and from other laboratories have demonstrated that the Hedgehog signaling pathway plays an essential role in the formation of the blood vessels that form the vascular network throughout the body. Curis is utilizing this biological property of the Hedgehog pathway to develop locally administered drug candidates to treat cardiovascular disorders such as heart attacks and peripheral vascular disease. NMT Medical Receives Approval for Migraine Headache Study Company’s STARFlex® PFO Closure Technology to be Evaluated NMT Medical, Inc. announced at the American Heart Association’s Scientific Sessions 2004 that it has received approval to initiate a clinical study in the United Kingdom designed to evaluate the effectiveness of transcatheter closure of a common cardiac defect, using its proprietary StarFlex® septal repair technology, in the treatment and prevention of migraine headaches. The NMT Medical sponsored clinical study, named MIST (Migraine Intervention with StarFlex Technology), is the first prospective, randomized, controlled study to evaluate the potential relationship between a patent foramen ovale (PFO) and certain migraine attacks, and whether sealing the PFO is an effective treatment in the resolution of these migraines. MIST is a double-blinded study randomizing migraine patients with PFOs to either PFO closure with the StarFlex implant or a control arm. Enrollment is expected to be completed during 2005. Study patients will be followed for six months. Andrew Dowson, MD, the Director of the King’s Headache Service, Kings College Hospital, London and co-primary investigator for MIST, said, Migraine is a widespread problem, affecting over 10% of the U.S. and European populations. Despite a wide range of pharmaceutical options available today, there is no cure; and for many patients, pharmaceutical options simply don’t work or are not well tolerated. Early reports from seven nonrandomized studies at different centers around Europe and the U.S. strongly suggest that PFO is a potential contributing factor in migraines. These studies have shown about a 50% elimination or reduction of migraine occurrence after an implant is in place. If we can achieve similar results in the MIST trial, we may validate the utility of the StarFlex implant in resolving some migraines. The PFO closure procedure using StarFlex takes approximately 30 minutes to perform in a cardiac catheterization lab. Patients can return to normal activity soon after the procedure. More than 14,000 PFOs have been closed globally with NMT’s implant technology. StarFlex is a fourth-generation design and is part of the Company’s CLOSURE I clinical trial in North America. CLOSURE I is evaluating the effectiveness of transcatheter closure of a PFO in preventing recurrent stroke and TIA (transient ischemic attack). StarFlex has been commercially available in Europe under the CE Mark since 1998. Siemens Introduces New Encompass Release for Acuson Sequoia Echocardiography Platform at AHA Integrated 3D Transesophageal (TEE) Imaging Announced on Acuson CV70 Cardiovascular System Siemens Medical Solutions introduced its new Encompass Release for the Acuson Sequoia C512 and C256 echocardiography systems. The new release includes Native TEQ dynamic ultrasound technology1, an image optimization technology that improves sonography workflow and ergonomics, and the new 8V3 transducer option for pediatric and fetal echocardiography exams. Native TEQ adds a new and much wanted dimension to echocardiography by taking away the subjectivity and operator dependence in image acquisition, said Manni A. Vannan, MBBS, FACC, professor of medicine, associate chief of cardiology, University of California at Irvine, Orange, Calif. The ability to place a transducer on the chest wall and have the machine give you an optimal picture immediately is a significant advance in ultrasound imaging. Additionally, the optimization is in real-time and independent of where you are scanning, and it has the potential to reduce sonographer repetitive stress injury due to less hand motion on the keyboard. Siemens’ Native TEQ technology enables the ultrasound system’s computer to read the signals that are returning from the individual patient, and then automatically adjust the parameters while the operator is scanning, so all images are optimized in real-time and the sonographer or physician can scan without having to touch the keyboard. There are no gain or depth-gain-compensation (DGC) control adjustments needed while scanning. The computer is programmed to perform advanced real-time motion analysis in addition to detecting and differentiating noise and artifacts from soft tissue. The image gain is automatically optimized in the axial and lateral dimensions in real-time, once the transducer touches the patient. The company also demonstrated new advancements on the Acuson CV70 cardiovascular system, such as fourSight transesophageal (TEE) view for integrated three-dimensional (3D) TEE imaging, and the new P9-4 transducer2 for pediatric cardiac imaging. Through advanced technology migration from the Sequoia system, 3D TEE imaging is now available with the CV70, enabling easier access to 3D/4D images through simple acquisition, review, manipulation and dynamic display capabilities of gated 3D datasets using the V5Ms TEE transducer. For TEE imaging, 3D surface or multiplanar reconstruction can provide physicians a more detailed, anatomical display of the heart and clinical disease processes, and with the V5Ms TEE transducer, physicians will have easier access to high quality 3D images. The company also displayed its new Acuson AcuNav 8F ultrasound catheter2 for visualization of vascular and cardiac anatomy and physiology, measurement of blood flow, and visualization of other devices throughout the entire heart. The AcuNav 8F catheter is 33 percent smaller in the cross sectional area than the existing AcuNav 10F catheter, enabling improved access during closure of atrial septal defects (ASD) on smaller patients, and left heart applications for both interventional cardiology and electrophysiology. 1. The Native TEQ Dynamic Technology requires a 510(k) review and is not yet commercially available. 2. The P9-4 and 8V3 transducers, and the AcuNav 8F ultrasound catheter are not yet commercially available. All trademarks are the property of their respective owners.