Breaking Up With MONA?
The invited discussant for this trial was Dr Karl B Kern (University of Arizona, Tucson), who pointed out that all cardiologists are familiar with MONA, which stands for morphine, oxygen therapy, nitrates, and aspirin.
“We were all taught that MONA is our friend anytime we met a cardiac patient with ischemic chest pain,” Kern said. “But this may be, with the AVOID trial, the beginning of her demise.”
Every good trial has to start with the pneumonic, he said wryly, “and I congratulate the AVOID trial. Should we avoid oxygen after the AVOID trial? Maybe so.”
Results of a Cochrane review on oxygen therapy released last year combined the small studies that have been done to date, he said, “and when combined, the data were clearly inconclusive. It actually suggested harm but was underpowered, so no real conclusion could be made.”
The current study took on that question, and in the prehospital setting, which makes it “even more remarkable,” Kern said. “They found, as they prespecified, that their primary end point of infarct size was significantly less without oxygen. That’s an astounding finding, and really one that I think will cause many cardiologists and physicians to take note and perhaps step back.”
That’s an astounding finding, and really one that I think will cause many cardiologists and physicians to take note and perhaps step back.”
He cautioned, though, that infarct size using biomarkers is still a surrogate end point, not hard clinical outcomes, and the use of biomarkers, “although admirable, is perhaps not today the most accurate.” What is accurate, on the other hand, is the use of CMR, “and the data held up at 6 months as well—with oxygen therapy there was a larger infarct.”
He raised a few issues, though, with the study. One is that they used 6 to 8 L/min of oxygen, while in the hospital phase “we would use less,” 2 to 4 L/min, particularly for this population of patients who were not hypoxic, Kern noted. “The effect of that extra oxygen is not known.”
Although the curves for oxygen saturation clearly separated in the trial, he said he would be interested to see blood gas measures, but these were not available since it was done out of hospital.
Finally, while they were secondary end points, there was an increase in significant arrhythmias and recurrent infarction in those given oxygen. “Certainly the arrhythmias could be explained by microvascular damage and ongoing ischemia, but perhaps not quite so with the recurrent infarctions, which are more typically plaque rupture during the hospital course before discharge,” he said.
“But I really congratulate the authors on this very provocative, if not in fact definitive, trial,” Kern said, and it will be of interest to see if there will ultimately be a mortality difference.
“So back to MONA,” he concluded. “Should we divorce her, or as Neil Sedaka said, at least break up? I guess I’m not quite ready to do that, but I’m certainly willing to date her less often.”
The study was funded by Alfred Hospital Foundation, FALCK Foundation, and Paramedics Australia. Stub reports research grants from the Royal Australian College of Physicians and Cardiac Society of Australia and other research support from St Jude Medical. The coauthors report no relevant financial relationships.