Key Points:
- The PULSE-MI trial assessed the effects of pre-hospital pulse-dose glucocorticoid on final infarct size in STEMI patients, revealing no significant reduction compared to placebo.
- Despite the lack of impact on final infarct size, glucocorticoid administration improved acute LVEF, reduced acute infarct size, and decreased the presence of microvascular obstruction.
- The trial confirmed the safety of pre-hospital glucocorticoid use, with no significant differences in adverse events between the treatment and placebo groups.
Inflammation in ST-segment elevation myocardial infarction (STEMI) is thought to be a contributor to both acute myocardial ischemia and reperfusion injury after primary percutaneous coronary intervention (PCI). Methylprednisolone is a glucocorticoid with potent anti-inflammatory properties and is used as an effective and safe treatment of a wide range of acute diseases. In this study, the authors examined the cardioprotective effects of pulse-dose methylprednisolone administered in the pre-hospital setting in patients with STEMI transferred for primary PCI.
The PULSE-MI trial, a double-blind, placebo-controlled, randomized clinical study, aimed to evaluate the efficacy and safety of administering a bolus of 250 mg methylprednisolone intravenous or matching placebo over a period of 5 min in the pre-hospital setting setting for patients presenting with ST-segment elevation myocardial infarction (STEMI) in Denmark. Conducted across multiple centers, the trial involved 742 randomized patients out of 1443 screened, with 382 receiving glucocorticoid and 360 receiving placebo.
The primary outcome of the trial focused on the final infarct size, measured as a percentage of the left ventricle (LV) on cardiac magnetic resonance (CMR) at three months. The results showed a mean final infarct size of 7.31% (95% CI: 6.31%–8.32%) in the glucocorticoid group compared to 8.04% (95% CI: 7.05%–9.03%) in the placebo group. Although the difference of -0.73% (95% CI: -1.02% to 0.31%) was observed, it was not statistically significant (P = 0.24).
Secondary outcomes revealed more promising results. The acute infarct size was significantly reduced in the glucocorticoid group (11.2% of LV) compared to the placebo group (15.5% of LV) with a P-value of 0.049. Moreover, the presence of microvascular obstruction (MVO) was lower in the glucocorticoid group (57%) than in the placebo group (68%), with a P-value of 0.041. Additionally, patients in the glucocorticoid group had a higher acute left ventricular ejection fraction (LVEF) at 53%, compared to 49% in the placebo group, which was statistically significant (P < 0.001).
Safety endpoints were closely monitored, and the trial confirmed the safety of glucocorticoid administration in the pre-hospital setting. The incidence of infections was similar between the two groups, with 4% in both the glucocorticoid and placebo groups experiencing one-time infections. Other adverse events such as skin complications and manic or delirious episodes were rare and did not differ significantly between groups.
The PULSE-MI trial demonstrated that while pre-hospital pulse-dose glucocorticoid does not significantly reduce the final infarct size in STEMI patients, it offers benefits in terms of reducing acute infarct size, improving acute LVEF, and decreasing microvascular obstruction. The treatment was found to be safe, with no significant increase in adverse events compared to placebo.
References:
- Madsen, J.M., Obling, L.E.R., Rytoft, L. et al. Pre-hospital pulse glucocorticoid therapy in patients with ST-segment elevation myocardial infarction transferred for primary percutaneous coronary intervention: a randomized controlled trial (PULSE-MI). Trials 24, 808 (2023). https://doi.org/10.1186/s13063-023-07830-y