Prehospital Pulse-Dose Glucocorticoid in ST-Segment Elevation Myocardial Infarction: The PULSE-MI Randomized Clinical Trial

Abstract

Importance: In patients with ST-segment elevation myocardial infarction (STEMI), acute inflammation is related to the extent of myocardial damage and may increase infarct size. Thus, administration of pulse-dose glucocorticoid in the very early phase of infarction may reduce infarct size.

Objective: To determine the cardioprotective effect of prehospital pulse-dose glucocorticoid in patients with STEMI.

Design, setting, and participants: This was a 1:1 investigator-initiated, blinded, placebo-controlled, randomized clinical trial conducted between November 14, 2022, and October 17, 2023, with last follow-up on January 17, 2024. Patients 18 years and older with less than 12 hours of acute chest pain and STEMI were included in the prehospital setting throughout the Region Zealand and Capital Region of Denmark and transferred to Rigshospitalet, Denmark.

Intervention: Patients were randomly allocated to intravenous glucocorticoid (methylprednisolone, 250 mg) or placebo in the prehospital setting.

Main outcomes and measures: The primary outcome was final infarct size on cardiac magnetic resonance (CMR) at 3 months. The power calculation was based on an anticipated final infarct size of 13%. Secondary outcomes included CMR outcomes on acute scan and at 3 months, peak of cardiac biomarkers, clinical end points at 3 months, and adverse events.

Results: Of 530 included patients (median [IQR] age, 65 [56-75] years; 418 male [78.9%]) with STEMI, 401 (76%) were assessed 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%; IQR, 2%-11% vs placebo, 6%; IQR, 2%-13%; P = .24). Compared with placebo, the glucocorticoid group had smaller acute infarct size (odds ratio, 0.78; 95% CI, 0.61-1.00), less microvascular obstruction (relative risk ratio, 0.83; 95% CI, 0.71-0.99), and greater acute left ventricular ejection fraction (mean difference, 4.44%; 95% CI, 2.01%-6.87%). Other secondary outcomes were similar in both groups.

Conclusions and relevance: In patients with STEMI, treatment with prehospital pulse-dose glucocorticoid did not reduce final infarct size after 3 months. However, the trial was likely underpowered as the final infarct size was smaller than anticipated. The glucocorticoid group had improved acute parameters compared with placebo.

Trial registration: ClinicalTrials.gov Identifier: NCT05462730.

Figure 1.. Study Flowchart

Shown is the study flowchart including postrandomization exclusions and the reasons hereof. The modified intention-to-treat population included all patients who fulfilled all eligibility criteria. Logistics refers to patients not being able to be transported to Rigshospitalet, Denmark, other refers to reasons such as poor hearing, chronic pain, or other reasons for not being able to complete a cardiac magnetic resonance imaging scan, primary outcome not evaluable refers to poor image quality and the readers have not been able to analysis the images for the primary outcome. SCAD indicates spontaneous coronary artery dissection; STEMI, ST-segment elevation myocardial infarction.

Figure 2.. Box Plots Illustrating Infarct Size in the Modified Intention-to-Treat Population

Shown are box plots of acute and final infarct size stratified by treatment group in the modified intention-to-treat population. A, Final infarct size (primary outcome). B, Acute infarct size (secondary outcome). Infarct size is reported as a percentage of the left ventricle. Acute refers to values on the acute cardiac magnetic resonance scan. Final refers to values on the follow-up cardiac magnetic resonance scan. The lower and upper hinges correspond to the first and third quartiles (the 25th and 75th percentiles). The upper whisker extends from the hinge to the largest value no further than 1.5 × IQR from the hinge (where IQR is the distance between the first and third quartiles). The lower whisker extends from the hinge to the smallest value at most 1.5 × IQR of the hinge. Data beyond the end of the whiskers are called outlying points and are plotted individually.

Figure 3.. Subgroup Analysis of the Primary Outcome: Wilcoxon-Mann-Whitney Odds Ratio (OR)

Shown is the subgroup analysis of median final infarct size at 3 months in each group and Wilcoxon-Mann-Whitney OR with 95% CI in the glucocorticoid group and placebo group. The widths of the CIs were not adjusted for multiple comparisons, and the reported CIs should not be used for hypothesis testing. CABG indicates coronary artery bypass graft; LAD, left anterior descending artery; LM, left main artery; PCI, percutaneous coronary intervention; TIMI, thrombolysis in myocardial infarction. ^aMissing: time from symptom onset to first wire, 10 in the placebo group and 7 in the glucocorticoid group. ^bMissing: time from study intervention to first wire, 10 in the placebo group and 7 in the glucocorticoid group. ^cMissing: time from first medical contact to first wire, 10 in the placebo group and 7 in the glucocorticoid group.