Download CTR 210 - Heart Failure Society of America

AdreView Myocardial Imaging for Risk Evaluation- A Multicentre Trial to Guide ICD Implantation in NYHA II&III HF
Patients with 30≤LVEF≤35 (ADMIRE-ICD)
Allen S Anderson; Wayne C Levy, Satish R Raj; Michael Davidson, Jonathan Rich; Ralph Brindis; William T Abraham; Silvia G Priori, Maryl R. Johnson, James Louis Januzzi; Derek V Exner; Jeroen Bax; Edward Miller;
Pamela S. Douglas; Sam Hedayat; John Camm; Faiez Zannad
Rationale
All patients with a reduced LVEF may not benefit from an implantable cardiac
defibrilator (ICD)1,2:
• About one-third of the total study population in MADIT II was classified as “lowrisk” and had a 2-year mortality of only 8%, receiving no benefit from an ICD3.
• Patients with an LVEF between 30-35% may not benefit from an ICD4.
• An ICD will prevent about two deaths per year for every 100 devices implanted
in patients with mild HF (NYHA II)5.
AdreView (Iobenguane I123 injection) imaging was FDA-approved in 2013 for
scintigraphic assessment of myocardial sympathetic innervation and may be useful in
selecting patients with HF who are at low-risk for SCD.
AdreView may be used to identify patients with lower 1- and 2-year mortality, as
indicated by an H/M ratio > 1.6.
Studies suggest that such patients may not benefit from an ICD6-8.
The aim of ADMIRE ICD is to demonstrate the efficacy of AdreView™ imaging for
guiding the decision of (ICD) implantation.
Arrhythmic Event
Primary Endpoint: All-cause mortality
Key Secondary Endpoints:
Rate of hospitalization and death related to major
complications of ICD implantation and a composite of
rate of complications of long-term device therapy
between low risk groups and between all patients in
AdreViewTM vs SOC groups.
-Cardiac death (SCD, death due to cardiac
arrhythmias, death due to HF, and death due to other
cardiovascular causes).
-Rate of all-cause hospitalization for CV cause.
-A composite of the occurrence of resuscitated lifethreatening ventricular tachycardia, unstable
ventricular tachy-arrhythmias, SCD and resuscitated
cardiac arrest.
-A composite of the occurrence of resuscitated lifethreatening ventricular tachycardia, unstable
ventricular tachy-arrhythmias, SCD and resuscitated
cardiac arrest.
Cumulative Rate (%)
The H/MN cut-off of 1.6 is
30
30
p=0.015
based upon published results in
ADMIRE-HF5 and ADMIRE-HFX9
20
20
studies, where AdreView
H/ M<1.60
uptake was prospectively
10
10
validated to discriminate
H/ M≥1.60
between patients at high and
0
0
low risk of mortality at 1 and 2
0
6
12
18
24
years.
Months Follow-up
Ethical Considerations
Besides withholding ICD for patients with an LVEF 30-35% and H/M ≥1.6, patients will
be managed according to standard of care. Physicians can manage changes in the
clinical status as needed. An independent Data Safety Monitoring Board (DSMB) will
oversee all safety aspects of the study. Monitoring will be performed on an ongoing
basis to detect any possible safety imbalance between groups to act upon accordingly.
Efficacy events will be adjudicate by an independent committee.
Trial Design
Inclusion criteria:
Ischaemic and nonischaemic stable HF
30%≤LVEF≤35% (by any
method except M-mode
echocardiography)
NYHA classes II and III
Exclusion criteria:
Existing ICD
Secondary prevention of
SCD
Unstable angina
Chronic renal insufficiency
(creatinine ≥3mg/dl)
Medication known or
suspected to inhibit
norepinephrine [NE]
transporter or reuptake, or to
deplete NE stores.
Heart transplant
H/M<1.6
High risk
ICD implanted
H/M≥1.6
Low risk
ICD not implanted
AdreView
R (1:1)
2nd AdreView
at 2 years F/U
AdreView
Patients and investigators blinded to AdreView results
ICD implanted as per guidelines
Up to 3 years individual follow up
F/U: Follow up
H/M: Heart to mediastinum ratio
R: Randomisation
SCD: Sudden cardiac death
GE Healthcare contact details:
Jose M Zubeldia, Medical director
[email protected]
Jay Chahal, Clinical Project Director
[email protected]
Trial details
Sample size: 2216 patients in 130 sites in North America and EU
Event driven: Efficacy analysis when 247 primary events are accrued
Data Safety Monitoring Board: Monitors safety, oversees conduct of the trial, recommends
changes to ensure favourable risk-benefit ratio
Clinical Events Adjudication Committee: Independently adjudicates efficacy
References
1. Goldenberg I, et al. Risk stratification for primary implantation of a cardioverter-defibrillator in patients with ischemic left ventricular dysfunction. J Am
Coll Cardiol. 2008; 51(3): 288-96. 2. Buxton AE, et al. Limitations of ejection fraction for prediction of sudden death risk in patients with coronary artery
disease: lessons from the MUSTT study. J Am Coll Cardiol. 2007: 50: 1150–1157. 3. Moss AJ, et al. Reduction in Inappropriate Therapy and Mortality
through ICD programming. New Engl J Med. 2012; 367 (24): 2275-83. 4. Al-Khatib SM, et al. Do patients with a left ventricular ejection fraction between
30% and 35% benefit from a primary prevention implantable cardioverter defibrillator? Int J Cardiol. 2014; 172(1): 253-4. 5. Ponikowski P, et al. 2016 ESC
Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur J Heart Fail. 2016 May 20. doi: 10.1002/ejhf.592. 6. Jacobson A 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. 2010; 55(20):2212-21. 7. Kawai T, et al. Usefulness of Cardiac Metaiodobenzylguanidine Imaging to Identify Patients with Chronic Heart Failure and Left Ventricular Ejection Fraction <35% at Low Risk for Sudden Cardiac
Death. Am J Cardiol. 2015; 115(11): 1549-54. 8. Chen J, Zhou W. I-123 metaiodobenzylguanidine imaging for predicting ventricular arrhythmia in heart
failure patients. Journal of Biomedical Research, 2013;27(6):460-466. 9. Narula J, et al. 123I-mIBG Imaging for Prediction of Mortality and Potentially Fatal
Events in Heart Failure: The ADMIRE-HFX Study. J Nucl Med. 2015; 56(7): 1011-8.
Sponsor/Financial Support
This study is fully funded by GE Healthcare
www.postersession.com