ADMIRE-HF Clinical Trial Published in the Journal of the American College of Cardiology

PRINCETON, N.J., May 17 /PRNewswire-FirstCall/ -- The ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) trial, the results of which were published in the May 18th, 2010 issue of the Journal of the American College of Cardiology, is a prospective study evaluating cardiac sympathetic nerve imaging using Iobenguane I 123 Injection (AdreView™) for identifying symptomatic heart failure patients most likely to experience cardiac events.

According to the study, the drug imaging results produced a model with four independent variables contributing to the prediction of the primary outcome events.

"Increased cardiac sympathetic activity is a prominent feature of heart failure and is associated with progressive deterioration and remodeling of the myocardium, inexorable decline in left ventricular function, and worsening symptoms," said Professor Roxy Senior, MD, Director of Cardiac Research Northwick Park Hospital, an author of the study.  "Our results suggest that in appropriately selected patients with heart failure, the 123I-mIBG imaging procedure can alert clinicians to the potential need for considering additional treatments."  

About the ADMIRE-HF Trial

ADMIRE-HF consisted of two identical open-label phase III clinical studies evaluating the cardiac sympathetic nerves at the cellular level.  The studies were conducted in 96 centers in North America and Europe.  Nine hundred sixty-four patients with New York Heart Association (NYHA) Class II (83%) and III (17%) heart failure (66% ischemic, 34% non-ischemic) and left ventricular ejection fraction (LVEF) less than or equal to 35% (mean 27.1%; median 29%) underwent early (15-minute) and late (four-hour) planar and single-photon emission computed tomography (SPECT) myocardial imaging.  Patients were then observed every six to seven weeks over the course of two years to monitor for occurrence of cardiac events.   The composite endpoint was the time to first occurrence of NYHA heart failure class progression, a potentially life-threatening arrhythmic event, or cardiac death, as determined by an independent adjudication panel.(1)

The researchers used the heart/mediastinum ratio (H/M) to assess the functionality of the sympathetic nerves; H/M is a ratio of the nerve function in the heart compared to that of a reference background region in the mediastinum (the mass of tissues and organs between the two pleural sacs, which separate the heart from the lungs). The study was designed to demonstrate that if the cardiac nerves are damaged or reduced in number, as reflected by reduced 123I-mIBG uptake in the heart, the patient is at increased risk for heart failure progression, arrhythmic events, and cardiac death.(1)

The primary analysis employed a Cox proportional hazards model to compare outcomes in subjects with H/M of <1.60 and greater than or equal to 1.60 on late planar imaging.  A multivariable Cox proportional hazards analysis incorporated imaging and clinical variables into a prediction model for adverse cardiac events.(1)

"Using imaging tests are consistent with current trends toward gaining improved and earlier understanding of heart disease at a molecular level and may enable preventive management strategies," said Arnold F. Jacobson, MD, PhD, Head, Cardiac Center of Excellence, GE Healthcare. "This testing method is not new, however ADMIRE-HF is the first large-scale multicenter prospective validation of the potential prognostic power and provides data that clinicians may be able to use to improve current practice."

ADMIRE-HF Results

The evaluable efficacy population consisted of 961 patients.  During the median follow-up period of 17 months, first cardiac events were observed in 237 patients (25%); these included 163 cases of heart failure progression, 50 arrhythmic events, and 24 cardiac deaths.  The risk of cardiac events (the trial's primary endpoint) was significantly lower for patients with an H/M greater than or equal to 1.60, with a hazard ratio (HR) of 0.40 (97.5% confidence interval [CI]: 0.25 to 0.64; p < 0.001). A Cox proportional hazards analysis based on a continuous numerical H/M (i.e., rather than on separating patients according to H/M greater than or equal to 1.60 or <1.60) revealed an even lower HR of 0.22 (97.5% CI: 0.10 to 0.47; p < 0.001).(1)

Survival analysis revealed two-year event rates of 15% for patients with an H/M greater than or equal to 1.60, compared to 38% for patients whose H/M was below 1.60. Hazard ratios for individual events, based on an H/M threshold of 1.60, were as follows: heart failure progression, 0.49 (95% CI: 0.32 to 0.77; p = 0.002); arrhythmic events, 0.37 (95% CI: 0.16 to 0.85; p = 0.37); and cardiac death, 0.14 (95% CI: 0.03 to 0.58; p = 0.006).(1)

A multivariate analysis of the pooled ADMIRE-HF data using only the planar 123I-mIBG imaging results produced a model with four independent variables contributing to the prediction of the primary outcome events: late H/M, left ventricular ejection fraction (LVEF), NYHA functional class, and plasma B-type brain natriuretic peptide (BNP).(1)

In subanalyses, the H/M provided significant information to complement BNP – a frequently used marker of prognosis in heart failure patients – for identifying patients at the highest risk for cardiac events and cardiac death. The two-year cardiac event rate for patients with BNP above the median of 140 ng/l was 42%, but among patients with H/M greater than or equal to 1.60, the rate was 20.5%. Whereas there were no cardiac deaths among the 57 patients with BNP >140 ng/l and H/M greater than or equal to 1.60, there were 42 cardiac deaths among the 406 patients (10.3%) with above-median BNP and H/M <1.60.(1)

The subanalyses also demonstrated a modest but statistically significant positive correlation between LVEF and H/M. The two-year cardiac event rate for individuals with LVEF <30% and H/M greater than or equal to 1.60 was less than half that of all patients with LVEF <30% (17.6% vs. 40.3%, respectively). There were two cardiac deaths among the 81 patients (2.5%) with LVEF <30% and H/M greater than or equal to 1.60, as compared with 39 cardiac deaths among the 409 (9.5%) patients with LVEF <30% and H/M <1.60. There were no cardiac deaths among the 120 patients with LVEF greater than or equal to 30% and H/M greater than or equal to 1.60.(1)

About Heart Failure

According to the American Heart Association, 5.7 million Americans suffer from heart failure. Cardiovascular disease in all its forms claims about as many lives each year as cancer, chronic lower respiratory diseases, accidents, and diabetes combined.  Patients who have previously suffered from heart failure have a sudden death rate that is six to nine times greater than the general population.(1)

About AdreView

AdreView™ (Iobenguane I 123 Injection) is a molecular imaging agent.  GE Healthcare began developing AdreView in 2004, and the agent was granted orphan-drug status by the Food and Drug Administration (FDA) in December 2006. In September 2008, AdreView was approved by the FDA for the detection of primary or metastatic pheochromocytoma or neuroblastoma as an adjunct to other diagnostic tests.  In the United States, it is not currently approved for use in cardiac imaging.

AdreView is approved in Germany, France, Great Britain, Spain, Belgium, Holland, Denmark, and Norway for the functional assessment of the cardiac sympathetic innervation.

Important Safety Information for AdreView

Hypersensitivity reactions have followed AdreView administration. Have anaphylactic and hypersensitivity treatment measures available prior to AdreView administration. AdreView contains benzyl alcohol (10.3 mg/mL) which may cause serious reactions in premature or low birth-weight infants. Patients with severe renal impairment may have increased radiation exposure and decreased quality of AdreView images. Failure to block thyroid iodine uptake may result in iodine 123 accumulation in the thyroid. Drugs which block norepinephrine uptake or deplete norepinephrine stores may decrease AdreView uptake in neuroendocrine tumors. When medically feasible, stop these drugs before AdreView administration and monitor patients for withdrawal signs and symptoms.

About GE Healthcare

GE Healthcare provides transformational medical technologies and services that are shaping a new age of patient care. Our broad expertise in medical imaging and information technologies, medical diagnostics, patient monitoring systems, drug discovery, biopharmaceutical manufacturing technologies, performance improvement and performance solutions services help our customers to deliver better care to more people around the world at a lower cost. In addition, we partner with healthcare leaders, striving to leverage the global policy change necessary to implement a successful shift to sustainable healthcare systems.

Our "healthymagination" vision for the future invites the world to join us on our journey as we continuously develop innovations focused on reducing costs, increasing access and improving quality and efficiency around the world. Headquartered in the United Kingdom, GE Healthcare is a $17 billion unit of General Electric Company (NYSE: GE). Worldwide, GE Healthcare employs more than 46,000 people committed to serving healthcare professionals and their patients in more than 100 countries. For more information about GE Healthcare, visit our website at www.gehealthcare.com.

(1) Jacobson AF, Senior R, Cerquiera MD, et al. Myocardial iodine‐123 meta‐iodobenzylguanidine imaging and cardiac events in heart failure: results of the prospective ADMIRE‐HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) study J Am Coll Cardiol. In Press

(2) American Heart Association Heart Disease and Stroke Statistics, 2009 Update  

SOURCE GE Healthcare