Beta-blockade early in the course of myocardial infarction was once fashionable – until COMMIT demonstrated an excess of early cardiogenic shock detracting from subsequent late, favorable effects. This led to beta-blockade initiation being deferred until after hemodynamic stability established.
This study, METOCARD-CNIC, is a trial of early intravenous metoprolol prior to primary PCI in patients with anterior STEMI. 270 patients were randomized over two years to receive IV metoprolol pre-reperfusion versus standard initiation following PCI. These two publications describe a surrogate outcome based on infarct size seen in follow-up MRI, and patient-oriented outcomes of 2-year MACE and heart failure progression. And, overall, it’s a good thing – infarct size at 1 week was reduced from 32.0 to 25.6 grams, and long-term MACE at median 2-year follow up was reduced from 18.3% to 10.8%.
However, long-term MRI follow-up at twelve months showed infarcted myocardium measured at 15.7 grams in the intervention group versus 18.2 grams in the control – no longer statistically significant. And, the patient-oriented outcome of MACE is a combined endpoint of death, heart failure admission, reinfarction, and malignant arrhythmias – with most of the separation in groups coming from heart failure admissions and malignant arrhythmias, as opposed to hard endpoints.
But, at the minimum, this is worth continuing to investigate. There are likely patients, such as this anterior STEMI cohort, with Killip Class II or lower at presentation, that reasonably have a greater chance of benefit than harm from early metoprolol. This is also quite small study – but taken in the context of the prior evidence, an argument could be made to cautiously re-introduce this treatment strategy, ideally as part of prospective investigation.
“Effect of Early Metoprolol on Infarct Size in ST-Segment−Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention”
http://www.ncbi.nlm.nih.gov/pubmed/24002794
“Long-Term Benefit of Early Pre-Reperfusion Metoprolol Administration in Patients With Acute Myocardial Infarction”
http://www.ncbi.nlm.nih.gov/pubmed/24694530
Your take on it pretty well parallels mine from when I first saw the Ibanez study (the second is new to me). I'm thinking it's probably a good idea in Killip I patients, and I'm looking forward to more study of Killip II's to really make sure it's safe for them since there's a pretty big jump in baseline risk for morbidity/mortality once you hit the latter class. Glad to see I'm in good company!
Yep, it's interesting to see this evidence evolve over the years. I always tell folks medicine isn't an "always" or "never" endeavor, and patient heterogeneity allows for significant practice variation based on individual factors. Need to keep working on pooling patients from these clinical trials to identify subgroups with potential benefit ….