Discussant Slides (PDF)

The AVOID Trial:
Is this the Demise of “MONA” ?
Karl B. Kern, MD
Professor of Medicine and
The Gordon A. Ewy, MD Distinguished Endowed Chair of Cardiovascular Medicine
University of Arizona
Co-Director, Sarver Heart Center,
Director, Cardiac Catheterization Laboratories
& the Interventional Cardiology Fellowship
Tucson, Arizona
Prospective, Randomized
Controlled Trial of
Oxygen Therapy for AMI
in those without overt
Timely !
Needed !
Done in the modern era of primary PCI !
The Cochrane Library 2013, Issue 8
Implications for Practice
The evidence in this area is sparse, of poor
quality, and predates the advances in
reperfusion techniques and trial methods of
recent years. The evidence available is
suggestive of harm but lacks power, so this
could be due to chance. Current evidence
neither supports nor clearly refutes the routine
use of oxygen in people with AMI.
The Cochrane Library 2013, Issue 8
Implications for Research
Given the widespread use of oxygen for AMI, the
inconsistencies in recommendations about when and
to whom it should be given, and the fact that the best
current evidence is suggestive of potential clinically
significant harm, we believe there is an urgent need
for an adequately powered randomized controlled trial
to establish the effectiveness of, or harm from, the
administration of oxygen to people with AMI. That
trial must incorporate contemporary standards in
design, conduct, analysis and reporting of trials and
address the spectrum, population and sample size
mentioned above to reflect contemporary diagnosis
and care of the patient with AMI.
The Cochrane Library 2013, Issue 8
Major Lessons from AVOID
• Routine oxygen therapy for AMI not necessary for
patients who are not hypoxic
• Unnecessary oxygen in such circumstances:
– May be harmful
• Increase MI size (Primary endpoint)
– Peak CK levels and CK AUC data greater with O2 Rx
(p=0.01 & 0.04)
– Peak TpI levels and AUC greater but not quite signif
(p=0.17 &0.12)
– 6 month CMR Infarct size
» Greater with O2 Rx (p=0.04)
Baseline Characteristics Between Groups
No O2
Heart rate
Ant MI
DTB time
54.0 min
56.0 min
TIMI flow post PCI
ECG ST resolution
Clinical Endpoints (secondary)
• Few in General
– Study powered for 1°endpoint (Cardiac enzymes)
(underpowered for clinical endpoints)
• More recurrent MIs and arrhythmias with O2
– Evidence of increased reperfusion injury?
• Trend for better survival with O2-Just Chance?
– Mortality: 4/218 with O2 and 10/223 without O2 (p=0.11)
Yet, Unanswered Questions
Actual PaO2 differences (torr), instead of just O2 Sats
Cardiac arrest literature suggests that > 300 torr oxygen detrimental.
Wonder what the curves in AVOID would look like for PaO2 ?
Yet, Unanswered Questions
• Details on:
– Eligible pts/Randomized pts (unblinded)
– Cross-overs (analysis was ITT)
– Statistical correction for multiple testing of 1°endpt:
CK peak (2 ways: geometric, median)
6 measurements for
the primary endpoint
TpI peak (2 ways)
– “Significant arrhythmias”-what were they?
Is it really the right time to break–up with ‘MONA’ and move on…
The data is certainly getting stronger, but is it definitive…??
I’m not sure, …
but I do know that “breaking up is hard to do”
Maybe we just date less often!