PULSE-MI Trial: Prehospital Pulse-Dose Glucocorticoids Fail to Reduce Long-Term Infarct Size in STEMI but Show Acute Benefits

The study, published in JAMA Cardiology found that prehospital administration of pulse-dose glucocorticoids did not result in a significant reduction in final infarct size after three months. Despite this, the trial did reveal some positive acute outcomes. Patients who received glucocorticoids showed improved immediate clinical parameters compared to those who received a placebo.

The researchers note that in patients with STEMI, acute inflammation is closely linked to the severity of myocardial damage and can contribute to an increase in infarct size. Therefore, administering pulse-dose glucocorticoids during the early phase of the infarction may help reduce the extent of myocardial damage. Jasmine Melissa Madsen, Copenhagen University Hospital, Copenhagen, Denmark, and colleagues aimed to determine the cardioprotective effect of prehospital pulse-dose glucocorticoid in patients with STEMI.

The 1:1, investigator-initiated, blinded, placebo-controlled, randomized clinical trial was conducted from November 14, 2022, to October 17, 2023, with the last follow-up on January 17, 2024. The study included patients aged 18 and older with acute chest pain lasting less than 12 hours and a diagnosis of STEMI. These patients were recruited in the prehospital setting across the Region Zealand and the Capital Region of Denmark and subsequently transferred to Rigshospitalet, Denmark.

Participants were randomly assigned to receive either intravenous glucocorticoid (methylprednisolone, 250 mg) or a placebo in the prehospital setting. The trial's primary outcome was the final infarct size assessed via cardiac magnetic resonance (CMR) at three months, with the power calculation based on an expected infarct size of 13%. Secondary outcomes included CMR results from acute and follow-up scans at three months, peak cardiac biomarkers, clinical endpoints at three months and any adverse events.

The following were the key findings of the study:

• Of 530 included patients (median age, 65 years; 418 male [78.9%]) with STEMI, 76% were evaluated for the primary outcome, with 198 patients treated with glucocorticoid and 203 with placebo.
• Median final infarct size was similar in the treatment groups (glucocorticoid, 5% versus placebo, 6%).
• Compared with placebo, the glucocorticoid group had smaller acute infarct size (odds ratio, 0.78), less microvascular obstruction (relative risk ratio, 0.83), and greater acute left ventricular ejection fraction (mean difference, 4.44%).
• Other secondary outcomes were similar in both groups.

The PULSE-MI trial results indicate that prehospital administration of pulse-dose glucocorticoids did not lead to a reduction in final infarct size after three months in patients with STEMI. Those receiving glucocorticoids exhibited improved acute outcomes, including higher left ventricular ejection fraction (LVEF), smaller acute infarct size, and reduced microvascular obstruction compared to those receiving a placebo.

"These initial benefits did not translate into long-term improvements in infarct size or left ventricular function during extended follow-up," the researchers concluded.

Reference:

Madsen JM, Engstrøm T, Obling LER, et al. Prehospital Pulse-Dose Glucocorticoid in ST-Segment Elevation Myocardial Infarction: The PULSE-MI Randomized Clinical Trial. JAMA Cardiol. Published online August 30, 2024. doi:10.1001/jamacardio.2024.2298