BARCELONA, SPAIN — Routine use of supplemental oxygen in patients with suspected acute MI (AMI) showed no benefit on all-cause mortality at 1 year in patients without hypoxia at baseline, in a new randomized trial[1].
Dr Robin Hofmann
Results of the Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction (DETO2X-AMI) were presented here at the European Society of Cardiology (ESC) 2017 Congress and published simultaneously in the New England Journal of Medicine.
Although there was also no harm seen with oxygen therapy, it still costs time and money, lead author Dr Robin Hofmann (Karolinska Institutet, Stockholm, Sweden) said during a press conference here. "It takes time to supply oxygen, and this time you can use for things that are actually good for the patient,"
Similarly, "oxygen is not expensive, but it's not free; in the US, there was a calculation of about $100 per patient per day, and now we're speaking of thousands, millions of patients with suspected myocardial infarction in the world," he added.
"Healthcare professionals have had a very strong belief in oxygen and also in the patients' desire to receive it, but the most common reason in our trial not to participate was that they didn't want oxygen," Hofmann said. Similarly, most patients who dropped out during the trial simply refused to continue with oxygen therapy.
"There was no particular reason for this—the patients just didn't want to have it, so I don't think in practice this is going to be a problem, to not use it anymore as much as we have before," he said.
Wide Use, Limited Evidence
Oxygen therapy has been used for more than a century and is still widely recommended by guidelines despite limited evidence, Hofmann noted. "The ESC gives it a class I, or a strong recommendation, based on a level of evidence C, which is expert opinion only," he said.
The rationale behind the recommendation is based on the belief that increased oxygen delivery to the ischemic myocardium reduces infarct size and subsequent complications such as heart failure or arrhythmias, Hofmann explained. "In recent years, a controversy has come up where experts have been arguing whether this widespread therapy has been more based on tradition than scientific fact, and there might even be risks involved," he said.
A negative effect of oxygen therapy in ST-segment elevation MI (STEMI) was reported in 2014 in the Australian Air Versus Oxygen in Myocardial Infarction (AVOID) trial, where researchers noted larger infarct sizes among patients receiving oxygen.
More recently, a Cochrane meta-analysis in 2016[2] concluded: "There is no evidence from randomized trials to support the routine use of inhaled oxygen in people with AMI, and we cannot rule out a harmful effect. Given the uncertainty surrounding the effect of oxygen therapy on all-cause mortality and on other outcomes critical for clinical decision, well-conducted, high-quality randomized controlled trials are urgently required to inform guidelines in order to give definitive recommendations about the routine use of oxygen in AMI."
To look at this issue further, the researchers conducted DETO2X-AMI, a registry-based randomized clinical trial based on the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry. SWEDEHEART is a national comprehensive quality registry of coronary care in which all 69 Swedish hospitals with a coronary care unit participate, "covering more than 90% of all the myocardial infarctions in Sweden per year," Hofmann noted.
Patients with suspected MI and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen, 6 L/min by open face mask for 6 to 12 hours, or ambient air. The trial was randomized but not double-blinded, which the researchers write was "not considered to be feasible or ethical." No patients were lost to follow-up for the primary end point, Hofmann noted.
A total of 6629 patients were enrolled, the researchers write. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation was 99% among patients receiving oxygen and 97% among those receiving ambient air.
Hypoxemia developed in 62 patients on oxygen (1.9%) vs 254 patients (7.7%) in the ambient-air group.
For the primary end point of death from any cause within 1 year after randomization, there was no significant difference seen between the groups.
DETO2X-AMI: Primary End Point
| End point | Oxygen, n=3311, n (%) | Ambient air, n=3318, n (%) | Hazard ratio (95% CI) | P |
|---|---|---|---|---|
| Death from any cause at 1 y | 166 (5.0) | 168 (5.1) | 0.97 (0.79– 1.21) | .80 |
The results were consistent across all subgroups, including patients with and without MI as a final diagnosis, males and females, age above or below the median, and across risk groups including smokers; patients with diabetes, chronic kidney disease, or anemia; patients with oxygen saturation below or above 95%; and patients with previous MI or previous PCI.
Rehospitalization for an MI at 1 year was also not different between groups.
DETO2X-AMI: Rehospitalization for MI at 1 Year
| End point | Oxygen, n=3311, n (%) | Ambient air, n=3318, n (%) | Hazard ratio (95% CI) | P |
|---|---|---|---|---|
| Rehospitalization for MI at 1 y | 126 (3.8) | 111 (3.3) | 1.13 (0.88–1.46) | 0.33 |
Myocardial injury assessed using the median of the highest troponin-T level occurring during hospitalization was 946.5 ng/L in the oxygen group vs 983.0 for those on ambient air, "virtually identical," noted Hofmann (P=0.97).
"In summary, in this pragmatic, registry-based randomized clinical trial evaluating supplemental oxygen vs ambient air in patients presenting with suspected myocardial infarction who did not have hypoxemia at baseline, we did not find a beneficial effect of oxygen treatment with respect to all-cause mortality at 1 year," he concluded.
Invited discussant for the trial here at the meeting was Dr David Newby (University of Edinburgh, Scotland), who called the results exciting and said they would change practice for AMI patients who are normoxic (>90% SaO2).
The results were "categorical," and all-cause mortality—an end point used because of the open-label design of the trial—is an "undisputable" outcome, he said.
"This fantastic trial has helped us answer a simple question, which is a nuisance when we're trying to manage our patients so we don't have to do it anymore," Newby said. "It will change the guidelines, and I would put it to you that we're moving into an era now where it's not sufficient just to use a phase 3 trial. We need to do proper clinical implementation trials where, when we implement it to the patients that we see in the clinic, does it have the benefit that we have [in the trial]? And we've had a resounding no for oxygen therapy in normoxic patients."
Definitive Evidence
In an editorial accompanying the publication[3], Dr Joseph Loscalzo (Brigham and Women's Hospital, Boston, MA) traces the roots of the use of oxygen therapy back to the late 1800s when it was first used to treat pneumonia and angina.
"Although the benefit of supplemental oxygen in patients with acute coronary syndrome who have hypoxemia is unimpeachable, its advantages in patients who do not have hypoxemia are far less certain," Loscalzo writes.
The results of the current study now "provide definitive evidence for a lack of benefit of supplemental oxygen therapy in patients with acute myocardial infarction who have normal oxygen saturation," he concludes.
"Although the mechanisms underlying physiological and biochemical adaptation to myocardial ischemia are complex, the answer to the question is straightforward, and its implications for coronary care are indisputable: supplemental oxygen provides no benefit to patients with acute coronary syndromes who do not have hypoxemia," he writes. "It's clearly time for clinical practice to change to reflect this definitive evidence."
The study was supported by grants from the Swedish Heart-Lung Foundation, the Swedish Research Council, and the Swedish Foundation for Strategic Research. Hofmann reports no relevant financial relationships. Disclosures for the coauthors are listed in on the journal website. Loscalzo is an editor-at-large for the New England Journal of Medicine. Newby had no relevant disclosures.
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Medscape Medical News © 2017
Cite this: DETO2X-AMI: No Mortality Benefit of Supplemental Oxygen in Acute MI - Medscape - Aug 28, 2017.
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