Can early steroids improve STEMI outcomes?
PULSE-MI trial tests high-dose methylprednisolone given pre-hospital
Inflammation is implicated in acute myocardial infarction in at least two ways:
Inflamed plaques are more likely to rupture and produce coronary occlusion.
A robust and potentially damaging inflammatory response occurs after reperfusion with coronary stenting.
It has been estimated that inflammation resulting from the reperfusion injury could produce as much as half of the eventual myocardial damage, significantly contributing to disability and death post-MI.
Inflammation’s negative effects in MI were recognized long ago; glucocorticoids were tested as a treatment for ST-elevation myocardial infarction (STEMI) in the 1990s and 2000s, and were found to be non-beneficial.
However, in those trials, glucocorticoids were given well after the onset of STEMI. It was hypothesized that much earlier treatment with steroids, i.e., by paramedics en route to the hospital, might improve outcomes.
PULSE-MI Trial
In a single region of Denmark, 530 patients with acute ST-elevation MI were randomized to receive either 250 mg methylprednisolone or placebo intravenously by paramedics in the community. All patients were then brought to a single medical center, where they underwent stenting of the culprit lesion.
Four hundred and one patients (76%) were assessed for the primary outcome (median size of the completed infarct).
There was no difference in the final infarct size between groups (5% vs. 4% of the left ventricle).
However, in the glucocorticoid group:
Acute infarct size was smaller (odds ratio 0.78, confidence interval 0.61-1.00)
Acute left ventricular ejection fraction was improved (+4.44%, CI 2.0%-6.9%)
There were no differences in other secondary outcomes.
The study was likely underpowered to detect a significant benefit, because (in what should be a familiar theme by now to readers of this newsletter) the authors overestimated the final infarct size and the expected benefit of the intervention.
Conclusion
PULSE-MI did not show a significant benefit of pre-hospital glucocorticoids for reducing final infarct size after acute ST-elevation myocardial infarction, but the trial was underpowered.
The interesting finding of benefit in acute infarct sizes and ejection fraction in PULSE-MI might invite further testing of glucocorticoids in STEMI, but (other than two small trials in Ukraine and Romania) no such investigations are currently listed on clinicaltrials.gov.