ADMIRE-HF Clinical Trial Published in the Journal of the American College of Cardiology
Iobenguane I 123 Injection Studied for Its Ability to Identify Risk in Patients with Symptomatic Heart Failure (HF)
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(TM)) 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(TM) (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
CONTACT: David Patti of JFK Communications, Inc.,
+1-609-514-5117, for
GE Healthcare
Web Site: http://www.gehealthcare.com/
Posted: May 2010
