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OUR MISSION: TO REDUCE THE BURDEN OF CARDIOVASCULAR DISEASE
Prof. Dan Atar,
PRO: Jose Sendon-Lopez (Madrid, Spain) CONTRA: Chaim Lotan (Jerusalem, Israel)
The first part of the session dealt with the controversy on oxygen supplementation in acute myocardial infarction. Professor Jose Sendon-Lopez of Madrid pointed to the basic pathophysiology of ischemia, namely the imbalance between oxygen supply and demand. He also reviewed reports on nocturnal desaturation of AMI patients leading to life-threatening arrhythmias. He then reviewed the recommendations from relevant guidelines on this topic. In fact, the ESC STEMI guideline of 2008 recommends oxygen supplementation by 2-4 liters/min in patients who are experiencing breathlessness, with a class of recommendation I and a level of evidence C. Similarly, the AHA NSTEMI guideline recommends oxygen with a class IIa, and a level of evidence C. The NICE recommendations of 2010 are also interesting to consider, in that they feature a recommendation in favor of oxygen supplementation in all AMI patients who have a oxygen saturation of up to 98%. Finally, Prof. Sendon-Lopez presented a recent Cochrane meta-analysis on this topic, and pointed to serious flaws of the included three studies in this meta-analysis, in that there was no statistically significant result in disfavor of oxygen therapy (10 versus 3 events, p=ns). Professor Chaim Lotan of Jerusalem opposed this stance by critically reviewing the beliefs of health professionals regarding oxygen therapy. He noted that in a survey, 50% of physicians stated that they thought oxygen would reduce mortality in AMI patients and another 24% thought that this treatment would alleviate pain. Only the remaining 26% were critical. He then systematically reviewed the documented negative effects of oxygen on certain physiological phenomena, such as the vasoconstriction of arteries induced by oxygen, a reduction of LAD flow in oxygen treated patients, an increase by 25% of coronary vascular resistance induced by oxygen, and even a reported reduction of stroke volume and cardiac output in oxygen treated experimental measurements in animals as opposed to room-air. He also referenced an important trial in humans, the AMIHOT study, in which AMI patients were randomized to either supersaturated oxygen or placebo, with a negative result. Finally, Prof. Lotan offered a personal view of a potential deleterious effect of oxygen supplementation in STEMI patients, namely the fact that the induced coronary vasoconstriction might lead to a tendency to stent-diameter undersizing, which in itself may predispose to an increased occurrence of in-stent stenosis. This part of the controversy session was concluded by the clear need voiced by both debaters and chairs for a large-scale randomized controlled trial on the use of oxygen supplementation in myocardial infarction.
PRO: Michel Ovize (Lyon, France) CONTRA: David Erlinge, Lund, Sweden The second part of the session addressed whether or not prevention of reperfusion injury in STEMI was needed. Infarct size is an important determinant of mortality and LV remodeling. On the pro position, Prof. Michel Ovize of Lyon, identified reperfusion injury as a major driver in the pathophysiology of acute MI. He reviewed seminal work that elucidated the pathophysiological mechanisms and addressed the concept of post-conditioning (Post-C) that seeks to prevent such injury. A large experimental body of evidence supports Post-C to reduce infarct size, adverse LV remodelling and increase ejection fraction (EF). Prof. Ovize then reviewed clinical data that seems to mirror such benefits (Sorensson 2010, Lonborg 2010, Mewton 2009 and 2011), but a greater area-at-risk in one study (Freixa 2011) illustrates that there might be possible detrimental effects by Post-C. Beneficial effects by Post-C were shown to be afforded by medical therapy (Ciclosporin A) as well. An important point was that infarct size mattered, i.e. the larger the infarcts, the greater post-C effects could be demonstrated; establishing proof-of-concept for this therapeutic approach. In a passionate rebuttal, Prof. Erlinge of Lund, referred to the field of cardioprotection as “40 years of futile efforts”. As in other sectors of cardiovascular pharmacotherapy, overwhelmingly positive experimental and pre-clinical data have not translated into favourable clinical outcomes. Key factors against cardioprotection would be the rapid onset of ischemia-reperfusion injury (IRI), the impossible task of delivering a drug to the area at risk prior to reperfusion (i.e. through the clotted artery), and the multitude of IRI-related pathways that could not easily be blocked. Also, the different coronary anatomy between man and animals, the existence of (pre-conditioning) stenosis, and concomitant medical therapy in patients vs animals were raised as important issues. Cardioprotection by repetitive forearm blood flow obstructions, so-called remote per-conditioning, did not show improvement in EF at 30 days. Finally, Prof. Erlinge illustrated that only small trials showed positive effects by cardioprotection. In a view shared by both presenters and chairmen, the need to investigate potential beneficial effects of cardioprotection/Post-C in large randomized trials was identified.
Controversies in acute coronary syndrome
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