The American Heart Association Scientific Sessions took place November 13-17, 2010 in Chicago. Enclosed below is a compilation of clinical news highlights from the meeting.
AHA: Prescription omega-3 No Better Than Placebo in Treating AFPrescription omega-3 fatty acids didn’t prevent the recurrence of the most common type of erratic beats in the heart’s upper chambers, according to late-breaking clinical trial research presented at the American Heart Association’s Scientific Sessions 2010. Efficacy and Safety of Prescription Omega-3 Acid Ethyl Esters (P-OM3) for the Prevention of Recurrent Symptomatic Atrial Fibrillation is a prospective, randomized, double-blind trial of 663 patients (average age 61, 56 percent male) enrolled at 96 sites. In the study, researchers compared the use of the fish-oil-derived product (4grams/day) and a placebo in patients with paroxysmal atrial fibrillation (AF). “This was an attempt to do a definitive study to find out if manufactured omega-3 is beneficial in patients with atrial fibrillation,” said Peter R. Kowey, MD, study author and chief of cardiology at Main Line Health Hospital System. “The major finding was that fish oil did not work.” Eating fish rich in omega-3 fatty acids benefits patients with some types of heart problems, including heart failure and heart attack. As part of a heart healthy diet, it is associated with reduced risk of sudden death and death from coronary artery disease in adults. Previous evidence of prescription omega-3 benefits in AF came from small studies in which researchers reported conflicting findings. The findings of this study don’t relate to omega-3 ingested from fish, Kowey said. “This was not a dietary study; this was a product manufactured from fish oil.” Some 2.66 million Americans currently have one of three forms of AF — paroxysmal, persistent and permanent — that increase the risk of fatal coronary heart disease, heart failure and stroke. Researchers randomly assigned 542 paroxysmal AF patients and 121 persistent AF patients to receive 4 grams of prescription omega-3 a day or a corresponding placebo. Treatment lasted 24 weeks. The trial’s primary endpoint was the time to the first recurrence of paroxysmal AF symptoms. Researchers found:
• Paroxysmal AF patients who received omega-3 didn’t differ significantly from the placebo group in the time to first recurrence of symptoms. • There was no significant difference between treated persistent AF and the placebo group. • The same result emerged after researchers combined data from both types of treated AF patients. • Prescription omega-3 proved safe and patients tolerated it well.“The trial’s major implication is that using prescription omega-3 in the vast majority of paroxysmal atrial fibrillation patients who do not have significant heart disease is fruitless,” Kowey said. “In the absence of any data that it works, it is probably better not to take prescription omega-3, simply because you don’t have to and it costs money.” The researchers’ findings applied only to paroxysmal AF. “We excluded AF patients with heart failure, so the possibility that the drug might work in those patients is not completely closed,” Kowey said. “However, we have never seen a drug that worked in a sicker group after it failed in a group less ill.” He said he didn’t believe that taking other doses of omega-3 would benefit people. “As far as I know, everybody who gets omega-3 prescribed takes a lower dose than we used in this study. I think it’s unlikely that if you took more, you would do better.” GlaxoSmithKline funded the study.
AHA: Standard Pacing Therapy Regulates Heart Pumping As Well As Costly Tailored MethodsStandard cardiac resynchronization therapy (CRT) is as effective as two other methods that regulate the time interval between the squeezing of the heart’s upper and lower chambers, according to late-breaking clinical trial results presented at the AHA’s Scientific Sessions 2010. The SMART AV trial included 1,014 heart failure patients (68 percent male, average age 66) at 100 sites in the US and Europe. Each patient had suboptimal atrioventricular (AV) interval delay, a condition in which the timing between the constrictions of the heart’s atria and ventricles is askew by milliseconds. In the study, researchers randomized 980 of the patients to one of the three therapies:
• The standard therapy of a pre-set AV interval of 120 milliseconds for the time delay between atrial and ventricle constrictions; • Echocardiography-customization of the AV interval determined after device implantation by an ultrasound examination of blood flow into the patient’s left ventricle and across the mitral valve (as recommended by the American Society of Echocardiography); • AV optimization by the SmartDelay™ algorithm, a technique derived from hemodynamic laboratory studies in humans. The primary endpoint was the volume of the left ventricle at the end of contraction. Its secondary endpoints were heart function; patients’ self-reported quality of life; improvement in walking for six minutes; the left ventricle’s volume at the end of relaxation; and its squeezing force while ejecting blood.At the end of the six-month trial, researchers found no significant difference in the primary or any of the secondary endpoints among the three patient groups. “These conclusions are quite important,” said Kenneth A. Ellenbogen, MD, lead author of the study and Kontos professor of cardiology and department chairman at the Virginia Commonwealth University School of Medicine in Richmond. “Routine AV optimization is not worth the time, the cost, or the effort because there is no detriment to using a device as it is programmed off the shelf.” However, he said that in patients who do not respond to this therapy, some technique for optimizing the AV interval may be useful. “We know CRT is tremendously effective,” Ellenbogen said. “It can decrease mortality and improve quality of life. It can increase heart muscle function and the amount of blood the heart pumps. In people with enlarged hearts, the size of the ventricular pumping chamber of the heart actually shrinks.” However, only about 70 percent of patients respond to CRT. So researchers have sought to improve the therapy by focusing on how to best resynchronize the heart’s upper and lower contractions. In a subanalysis of the women in the study, the researchers found that those treated with AV optimization, both echocardiography and SmartDelay, did significantly better with respect to the primary endpoint compared to those treated with the preset program. The results showed the importance of large clinical trials, Ellenbogen said. “We should never assume that just because something makes sense from a physiologic point of view, or has been studied in small numbers of patients, that we should automatically expect that it will make a big impact on patient outcomes,” he said. Boston Scientific of Natick, Mass., funded the study.
St. Jude Medical Announces Results of ASSERT Study Demonstrating Effectiveness of Implantable Device Monitoring in Predicting StrokeSt. Jude Medical, Inc., a global medical device company, announced the results of the ASymptomatic AF and Stroke Evaluation in Pacemaker Patients and the AF Reduction Atrial Pacing Trial (ASSERT), a St. Jude Medical sponsored trial conducted by the Population Health Research Institute of McMaster University and Hamilton Health Sciences in Hamilton, Canada. The trial demonstrated that pacemaker patients without history of atrial tachycardia (AT) or atrial fibrillation (AF) who have device-detected arrhythmias are approximately 2.5 times more likely to have a stroke than patients who don’t have device-detected arrhythmias. The results of the trial were presented by Dr. Jeff S. Healey, principal investigator for the arrhythmias program at the Population Health Research Institute, during the “Clinical Science: Special Reports” session at the American Heart Association Scientific Sessions 2010. “These results are significant because they demonstrate that even brief, asymptomatic AF episodes can cause a stroke, and that the proportion of strokes that are associated with atrial arrhythmias is much higher than previously thought,” said Dr. Healey. “This trial shows that by using the information already available in implantable pacemakers and defibrillators, physicians can identify patients at risk for stroke, earlier than would otherwise be the case, even before they experience arrhythmia symptoms.” ASSERT studied 2,580 pacemaker patients over the age of 65 with hypertension and no history of AF. The trial was a cohort study designed to determine whether the detection of arrhythmias using pacemaker-based diagnostics predicts an increased risk of stroke in elderly, hypertensive patients without any history of AF. Atrial fibrillation had previously been linked to an increased risk of stroke but it was not clear that brief, often asymptomatic AF episodes are associated with an increased risk for stroke as well. Technologies such as the AT/AF diagnostic data and alerts available in St. Jude Medical implantable devices, including the Accent™ pacemaker and Fortify™ ICD (implantable cardioverter defibrillator), via the Merlin.net remote monitoring system, allow physicians and patients to be notified whenever a patient experiences significant atrial arrhythmias such as AT or AF. “These results further demonstrate the value of the arrhythmia monitoring algorithms and alerts offered in St. Jude Medical pacemakers and implantable defibrillators,” said Dr. Mark Carlson, chief medical officer and senior vice president of research and clinical affairs for the St. Jude Medical Cardiac Rhythm Management Division. “This study reaffirms our commitment to providing physicians with the clinically relevant information that allows them to deliver more timely and effective care.”
Landmark Medtronic-Supported Study Shows CRT-D Reduced Mortality By 29 Percent in Mildly Symptomatic Heart Failure PatientsMedtronic, Inc. announced that the landmark RAFT (Resynchronization/Defibrillation for Ambulatory Heart Failure Trial) clinical trial shows Medtronic cardiac resynchronization therapy- defibrillators (CRT-Ds) significantly reduced mortality for mildly symptomatic heart failure patients (NYHA Class II) by 29 percent when compared to patients treated with guideline-recommended implantable cardioverter-defibrillators (ICDs) and medical therapy. The RAFT data also demonstrated a significant reduction (27 percent) in combined mortality and heart failure hospitalizations for this population consistent with previously published studies. The use of Medtronic CRT devices for mildly symptomatic heart failure patients (NYHA Class II) is investigational and not an approved use in the United States. The findings from the RAFT clinical trial were released at the late-breaking clinical science session at the Scientific Sessions 2010, the annual congress of the American Heart Association, and published online in the New England Journal of Medicine. “These landmark findings demonstrate that earlier intervention with CRT-D, in addition to guideline-recommended medical and ICD therapy, saves lives in this patient population,” said Anthony Tang, MD, RAFT principal investigator, professor of medicine at the University of British Columbia and adjunct professor of medicine at the University of Ottawa Heart Institute in Ottawa, Canada. “Even for patients without major restrictions from their heart failure, CRT has been shown to slow the progression of their disease and reduce heart failure hospitalizations.” More than 22 million people worldwide – including 500,000 Canadians and 6 million patients in the United States1 – have heart failure, a condition in which the heart cannot adequately pump blood through the body. Cardiovascular mortality has declined over the last three decades; however, the mortality rate for heart failure is rising.2 Additionally, heart failure is the most costly cardiovascular disease in the United States at an estimated cost of nearly $40 billion per year.1 Cardiac resynchronization therapy reduces heart failure symptoms as well as hospitalizations and mortality for some patients with moderate to severe heart failure (New York Heart Association, or NYHA, Class III and ambulatory Class IV). The RAFT trial investigated whether patients with mild to moderate heart failure (NYHA Class II and III) could benefit from cardiac resynchronization therapy in conjunction with ICD and medical therapy. Both the mortality alone and the combined mortality and heart failure hospitalization endpoints for all patients in the study were reduced by 25 percent. “This Medtronic-supported research is the first to show the significant lifesaving value of CRT-D for mildly symptomatic heart failure patients and builds upon the growing body of evidence calling for guideline changes,” said Pat Mackin, president of the Cardiac Rhythm Disease Management business and senior vice president at Medtronic. “Our goal is to ensure heart failure patients who could benefit from our therapies are able to receive them.” Medtronic has supported seven major heart failure studies that have contributed to guidelines, including SCD-HeFT, REVERSE, MIRACLE, MIRACLE ICD, MIRACLE ICD II, MUSTIC, and CARE HF studies. First published in December 2008, the Medtronic-sponsored REVERSE (Resynchronization Reverse Remodeling in Systolic Left Ventricular Dysfunction) clinical trial was the industry’s first study showing the benefit of CRT for mildly symptomatic patients. About RAFT A double-blinded, randomized, controlled trial, RAFT was led by the University of Ottawa Heart Institute and jointly supported by grants from the Canadian Institutes of Health Research (CIHR) with financial support from Medtronic of Canada. A total of 1,798 mild to moderate heart failure (NYHA Class II and III) patients with ejection fraction of ≤ 30 percent, and a QRS duration ≥ 120 were enrolled in the study at 34 centers in Canada, Europe, Turkey and Australia. Eighty percent (1,438) of the patients had NYHA Class II symptoms at enrollment. Patients were followed at least 18 months, and had an average follow-up of 40 months, making it the longest follow-up and largest patient months of experience of any study of CRT therapy. The study used Medtronic ICDs and CRT-Ds. The primary outcome was a composite of total mortality and heart failure hospitalization; secondary outcomes included death by any cause, death from cardiovascular cause and hospitalization for heart failure. Caution: The use of Medtronic CRT devices for mildly symptomatic heart failure patients (NYHA Class II) is investigational and not an approved use in the United States. 1American Heart Association / American Stroke Association, Heart Disease and Stroke Statistics, 2010 Update 2NHLBI, M.a.M., 2007 chart book on cardiovascular, lung, and blood diseases. http://www.nhlbi.nih.gov/resources/docs/07-chtbk.pdf
Rivaroxaban Significantly Reduces Risk of Stroke in Patients with Atrial Fibrillation with Comparable Safety versus Warfarin in Pivotal Phase III StudyBayer announced the results from the pivotal, double-blind Phase III, ROCKET AF trial. In the study, rivaroxaban demonstrated superiority to warfarin in reducing the risk of stroke and non-CNS systemic embolism in patients with atrial fibrillation (AF). Importantly, rates of bleeding were similar to warfarin, and bleeding events most concerning to physicians and patients, including intracranial hemorrhage, critical organ bleed, and bleeding-related death, were significantly lower in the rivaroxaban group. The results were presented as a late-breaker at the American Heart Association Scientific Sessions 2010. “Atrial fibrillation and stroke devastate the lives of millions of patients and their families worldwide every year. Anticoagulation with warfarin is effective in preventing strokes in patients with atrial fibrillation and has been the standard of care for more than half a century. However, its use in clinical practice is associated with many limitations,” said Professor Werner Hacke, Chair of the Department of Neurology at the University of Heidelberg, Germany, and member of the ROCKET AF Executive Steering Committee. “The ROCKET AF study has shown that once-daily rivaroxaban promises patients improved protection from stroke, with good safety and added convenience.” With 14,264 patients randomized, ROCKET AF is the largest double-blind study undertaken in the prevention of stroke in patients with AF, comparing once-daily rivaroxaban to dose-adjusted warfarin. For the primary efficacy endpoint, rivaroxaban was superior to warfarin, delivering a 21% relative risk reduction in stroke and non-CNS systemic embolism in the pre-specified on treatment population (1.70% vs. 2.15%, p=0.015). Additionally, in the intent to treat (ITT) population which followed all patients randomized in the trial until its completion, whether or not they completed the full course of therapy or switched to other options, rivaroxaban showed comparable benefits to warfarin (2.12% vs. 2.42%, pAbout ROCKET AF ROCKET AF (Rivaroxaban Once daily oral direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) was a prospective, randomized, double-blind, double-dummy parallel group outcomes study comparing once-daily rivaroxaban (20 mg, or 15 mg for patients with moderate renal impairment) with dose-adjusted warfarin in 14,264 patients with non-valvular atrial fibrillation who were at risk for stroke or non-CNS systemic embolism. This was an event-driven trial, which ended when the pre-specified number of efficacy events was accumulated. The primary objective of ROCKET AF was to demonstrate the efficacy of once-daily rivaroxaban as non-inferior to well controlled warfarin in the prevention of stroke and non-CNS systemic embolism in patients with non-valvular AF. The principal safety measure of ROCKET AF was the composite of major plus non-major clinically relevant bleeding events. The patients with AF evaluated in ROCKET AF typify those who are treated today by physicians with an anticoagulant to help reduce the risk of stroke. About Rivaroxaban Rivaroxaban is a novel oral anticoagulant that was invented in Bayer HealthCare’s Wuppertal laboratories in Germany, and is being jointly developed by Bayer HealthCare and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. It has a rapid onset of action with a predictable dose response and high bioavailability, no requirement for coagulation monitoring, as well as a limited potential for food and drug interactions. Rivaroxaban is marketed under the brand name Xarelto® for VTE prevention in adult patients following elective hip or knee replacement surgery, and it is the only new oral anticoagulant that has consistently demonstrated superior efficacy over enoxaparin for this indication. Xarelto® is approved in more than 100 countries worldwide and has been successfully launched in more than 75 countries by Bayer HealthCare. The extensive clinical trial program supporting rivaroxaban makes it the most studied oral, direct Factor Xa inhibitor in the world today. More than 65,000 patients are participating in the rivaroxaban clinical development program evaluating the product in the prevention and treatment of a broad range of acute and chronic blood-clotting disorders, including VTE treatment, secondary prevention of acute coronary syndrome, and VTE prevention in hospitalized, medically ill patients. If approved by the FDA, Ortho-McNeil, a division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. (a Johnson & Johnson Company), will commercialize rivaroxaban in the U.S. The U.S. Bayer HealthCare sales force will support the Ortho-McNeil sales force by detailing rivaroxaban in designated hospital accounts. Bayer HealthCare is exclusively responsible for the marketing of rivaroxaban in countries outside the U.S. For more news from the meeting, please see www.newsroom.heart.org.